Dr. Aristo Vojdani discusses the Early Detection and Prevention of Autoimmune Diseases at the Functional Medicine Discussion Group meeting on January 25, 2024 with moderator Dr. Ben Weitz.  

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Podcast Highlights

6:52  Predictive Autoimmunity.  Antinuclear antibody, ANA, is the best overall screen for autoimmunity and if the person is ANA positive, there is a high probability of autoimmune disease in the next 5-10 years.  There has been a sharp increase in the positivity of ANA in the US population, which corresponds to the rise in autoimmune diseases, which is likely due to our toxic environment. 

16:19  Autoimmunity.  Autoimmunity is a condition that takes years to develop.  Stage 1 is silent autoimmunity where testing will indicate auto-antibodies but the patient does not have any symptoms. Stage 2 is when the antibodies are elevated and there is some symptoms and a minimal loss of function. Stage 3 is when you have elevated antibodies, significant symptoms, other labs abnormal, and lots of loss of function.  The goal of immunology is to detect stage 1, so you can then find and remove the triggers in order to prevent full blown autoimmune disease.

                                          

 



Dr. Aristo Vojdani is the Father of Functional Immunology and he has dedicated his life’s research to helping us figure out what are the triggers for autoimmune diseases and many of the tests he has developed for Cyrex Labs are focused on this.  Dr. Vojdani has a PhD in microbiology and immunology and he has authored over 200 scientific papers published in peer reviewed journals. Dr. Vojdani is the co-owner of Immunosciences Lab in Los Angeles, which offers testing for various types of infections, including Lyme Disease. He is the Chief Science advisor for Cyrex Labs, whom he has developed all of the testing for, including the Lymphocyte Map test, Array 2 for Leaky Gut, and Array 5, The Multiple Autoimmune Reactivity Panel, and from Immunosciences, the Autoimmune Viral Trio Panel

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

 



 

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.  Welcome everybody. We’re going to get started. I’d like to introduce Steve Snyder. Steve, why don’t you come on up, and tell us about Integrative Therapeutics, which, we appreciate, is one of our sponsors this evening.

Steve:                                  No bright lights though. Hi, I’m Steve. Most of you know who I am. Is that working?

Dr. Weitz:                            Yeah. Hold it close to your mouth.

Steve:                                  Like that?

Dr. Weitz:                            Yeah.

Steve:                                  So, normally, we have samples and literature stuff, but because it’s the new year and we’re rebranding, we don’t have any of that stuff now, but I’m going to mention a couple of products, and if you’re interested in any of them, we can just connect and I can get you full sized trials of them.  For autoimmune, we have 3 ones in mind to talk about. One of them is our Glutathione Cell Defense. Quicksilver has done a really good job of convincing everybody that you have to have liposomal glutathione to increase glutathione levels. That’s not true. We happen to have one that has been shown to increase glutathione levels at a dose dependent manner. It’s a higher potency, less expensive per milligram, and less expensive per day than the Quicksilver one. It’s in capsule form. It’s a great product.

                                                The other one I wanted to mention, and if you’ve been here before, we mention it for every topic, because it’s good for everything, is the Curalieve, which is our new high bioavailable curcumin. If you’re familiar with our Theracurmin, it’s about 5 times more bioavailable than Theracurmin. So, some of the guys that helped create Theracurmin spun off on their own. They created this new product. They came to us and said, “Hey. We think this is better. We’d like you to market it for us.” And we looked at it, and went, “Ugh, God, it’s better.” So now we have both. We’re not discontinuing Theracurmin, but the Curalieve is the real deal. New delivery technology, not a whole lot more expensive.

                                                And then, the other one that we want to talk about real quick is vitamin D. It’s not anything sexy, but we have some really, really tasty chocolate chewable vitamin D tablets that everybody who uses them loves them. So, all of those are something that I’m happy to let you try, and just find me later, and we can talk about that.

Dr. Weitz:                            By the way, if you happen to be watching or viewing this on Apple or YouTube, these offers are for practitioners only.

Steve:                                   Good point. Yeah.

Dr. Weitz:                            Heather Sunshine from Cyrex.

Steve:                                  Integrative Therapeutics, yeah.

Dr. Weitz:                            Please come up and tell us about Cyrex Labs, our other sponsor here this evening. Thank you for that.

Heather:                              Hello everyone. My name is Heather Sunshine. I think most of you guys probably know me in the past as Heather Ngo. So, I recently got married, and you know why I didn’t appear at the last meeting, right? So anyway, I am going to be territory manager at Cyrex Laboratories. We are a specialty lab. We focus on environmentally induced autoimmunity. We understand the environment plays a huge role, such as the foods that we eat, and chemicals that we’re exposed to, pathogens, so those are in our environmental trigger panels. And then, we also have barrier panels, since we understand that’s the gateway to autoimmunity. Neural autoimmunity.  So we have intestinal permeability screen, our blood-brain barrier [inaudible 00:04:03]. And this is a serum kit, okay? And it is done by ELISA methodology, which sets us apart from all the other labs. This is our 4 pillars of excellence. We have antigen purification system, because Dr. Vojdani understands that a test is only as good as the purity of the antigen. We also optimize antigen concentration. We understand that each food have different proteins, so we validate each and every single one. You get a reference range specifically to that food. And then we also do side by side testing, duplicating. And then we also have our flow cytometry test, which is our Lymphocyte MAP test, which is an advanced laser technology, providing you with B-cells, T-cells, natural killer cells,  [inaudible 00:04:55] providing you ratios, counts, and percentages, so looking at your immune system right now.  So, I have a lot of materials at my booth. Please come by and grab those. And if you don’t want the hard copy, I can send you a PDF as well. Thank you so much.

Dr. Weitz:                            Thank you, Heather. And our speaker for this evening, the esteemed Dr. Aristo Vojdani, the father of functional immunology. And he’s going to be speaking about the Early Detection and Prevention of Autoimmune Diseases. Dr. Vojdani has a PhD in Microbiology. He’s a very prolific researcher. He’s published hundreds of scientific papers. I’m a member of ResearchGate. I don’t know if you’re on there, but constantly, another paper by Dr. Vojdani. He’s just unbelievable. And he’s also published 2 books. He’s the CEO and Technical Director for Immunosciences Lab. And he’s the Chief Science Officer for Cyrex Labs, and he’s developed all of their tests. He’s also a professor at the Department of Preventive Medicine at Loma Linda University. He was awarded the Linus Pauling Award, and he was also awarded the Lifetime Achievement Award by Jeffrey Bland, Personalized Lifestyle Medicine Institute. Dr. Vojdani, thank you.

Dr. Vojdani:                        Thank you, Ben. And I’m extremely happy to be here in person, finally, finally. And all of us wish you optimal health. Thank you. Okay.  So, as you and I get about 30 different journals every month, immunology related medicine [inaudible 00:06:50] journal. And, in past 2-3 years, I read more and more articles about predictive immunology, predictive immunology. And that’s what all of you are doing. So, tonight, specifically, I’m going to talk about maybe predictive autoimmunity, which is major part of predictive immunology.

                                                So, I decided to start with this slide. Just look at the title. You know what is ANA, antinuclear antibody. All of you know what it is? Antinuclear antibody is the best test for screening for autoimmunity, majority of them. If ANA is positive, probability of the next 5-10 years the person will develop some kind of autoimmune disease is very, very high.  So, up to like 5 years, 10 years ago, they were looking at antinuclear antibody, and in healthy population, so called, found between 3-5% had antinuclear antibodies.  And, because they didn’t have any symptoms of autoimmune disease, either they just disregard that, antinuclear antibodies.  So, Dr. Frederick Miller, who, I think retired about a year ago, before that published this fantastic article in Archives of Arthritis and Rheumatology, where he looked at occurrence of antinuclear antibodies between 1990-2000 something, 10, 12, in 15 years, and he found that, you see the increase. So, in 1970, let’s say it was only 8%, sharp increase in positivity of our U.S. population. So the question I am asking, what do you think the reason is?  This is indication of the rise of autoimmunities. Please.

Dr. Yahner:                         Exposure to a toxic environment.

Dr. Vojdani:                        Thank you very much. I’m glad you did not mention improvement in testing. Okay. That’s what rheumatologists are saying. But believe me, I work in clinical lab for past 40 years, 50 years. They’re saying that the technology we used to use 40 years ago, we are using the same method. Nothing has changed. So don’t try to sell me that. So, thank you so much. Okay. Now, that’s one issue.

                                                The second issue is this. Our genome is different from each other. Our fingerprint is different from each other. Our immune print is different from each other. So the question I’m asking… three different individuals, if you look up there, with three different immune prints… let’s take like 10 different individuals. Six of them will be in the middle, only 6 of them. They enjoy from balanced immune system. They are in the right sweet spot. Three of them will have hyperactivation of the immune system. One of them, hypoactivation of the immune system, autoimmunity and immune deficiency. So, why is it then, when we get sick, when I got sick from COVID, I went to see the when I went to Cedar’s Sinai, they put me right away on dexamethasone, without looking whether I was falling in the middle, in the right, or to the left. I was lucky that I was among this group. I had hyperactivation of the immune system, and the cytokine storm and all of that, so this medication helped.  But think about that individual, what dexamethasone would do to that person. Probably will kill that person. So, we cannot take everybody and say, “Okay, one medication for all.” That’s why the beauty of personalized medicine, and also, in scientific journals, we read a lot about personalized treatment.

                                                So, the other thing is, the third thing I would like to say, when we do measurements, there are 3 groups. There is a pattern. So, if you look at total immunoglobulin in the middle, that’s the best level of total IgG. Start from 700 all the way to 1,500, but to me, that’s the best, around 1,000. This individual is at 1,812. It’s very high, so hyperactivation of the immune system. Ask yourself. And then that individual, low total IgG. And if you look at secretory IgA, there is a pattern, also is low. Then, TNF alpha is low. That is humoral immunity, the soluble factors in the blood.  We look at cell-mediated immunity. The lymphocytes are low. B-cells are low. CD4/CD8 ratio is low. Here is high. F1 is in the middle. So therefore, there is a pattern, correlates with each other. And the main reason is that, the person having low total IgG, who is making the IgG? The B-cell. So, don’t be surprised why we have no B-cells. And the same with the visual. So, the same thing. So therefore, there is a pattern in the immune system. And that’s why we measure so many tests simultaneously in order to detect, to increase that detection, probability of detection of immune disorders by testing more components of innate adaptive immunity, humoral cell-mediated immunity, and mucosal immunity.

                                                So, yesterday, I gave a lecture through Rupa, and the lecture was about systems immunology. What I was talking about right now is all about systems immunology. And system immunology is really, you have to look at the immune system as a whole, holistic. Cannot look at IgG only without looking at B-cells, which is producing it. Right?   So, just look at the title of this article from August 2023, “Making Human Immune System More Interpretable Through Systems Immunology,” and then, “Predictable Human Immunology Boasts Implications for Better Diagnostics and Purity Precision in Patient with Infections and Immune-Associated Diseases.” That’s almost everything. 

So, now, let’s talk about autoimmunity. We do not go to bed, wake up in the morning with autoimmune disease. It takes many years to develop an autoimmune disease. So, the green is the ideal place to be. But then there are 3 different stages of autoimmunity. Stage 1, which is silent autoimmunity, you do testing, like ANA, rheumatoid factor, immune complexes, [inaudible 00:17:10] antibody, mitochondrial antibodies, and then you see some elevation, but patient doesn’t have any symptoms. So that’s 1. Stage 2 is, antibodies are elevated with some symptoms and loss of functionality, some. And then, of course, stage 3 is elevated antibodies, significant symptoms, and signs of lab and other types of abnormal, and lots of loss of function.  And so, the art of immunology, the art of medicine, is to detect at least at the stage 1. So, by finding the triggers, as you said before, try to remove the triggers, and prevent progression from stage 1 to stage 2 and stage 3. I think this is the central message.

                                                Now, let me share with you also very important information. Again, the reference is right there, published in Journal of Autoimmune Disease, or Autoimmunity, where Dr. Ma, or Professor Ma, looked at predictive antibodies for different autoimmune diseases. And again, in the interest of time, I choose only one slide from very important article.  So, first of all, we know that genes plus environmental factors play a role in autoimmunities. Gene is one third, environment is other two third. Okay? So that’s given. So, they found that antibodies appeared in the blood 3 years after 19 years for some disorders. Look at anti-mitochondrial antibody, so the antibody we produce against our own mitochondria. And then, for almost 19 years, we do not develop, for example, liver autoimmunity. But, in other cases, maybe 3 years, anti-myelin basic protein antibodies are detected 3 years before development of multiple sclerosis. So therefore, these antibodies, even 3 years, can help us to stop, at least, progression of autoimmune diseases. That’s why it’s important to do testing.

                                                Another slide, which I like, that the antibody is a driver, but is a crazy driver. He’s driving 250 miles per hour with Toyota. Okay? Now, if T-helper 1 and T-helper 17, the car also crazy, together, that car will have an accident, and that accident is going to be an autoimmune disease. So there is collaboration between antibodies and cell-mediated immunity as well, that we should not forget that. We call Th1 and Th17 autoreactive lymphocytes. They are important for our functionality, but, these are the one that cross the blood-brain barriers and attack the neurons, or they release, for example, IL-17, which is a cytokine, and that cytokine can activate microglia and other cells to attack the neurons. So, this is the panel that we view at Immunosciences Lab. It’s not very expensive.

Dr. Weitz:                            Are these T-cell mediated factors also triggered by the same types of triggers for antibodies?

Dr. Vojdani:                        Yes. Yes. Thank you for asking. Example, very well established that T-helper 17 become activated with too much salt. Very well proven. And infections, toxic chemicals can activate T-helper 17, T-helper 1 as well.

                                                So, there, gene plus environmental factors, food, infections, toxic chemicals, and their effect on our gut microbiome, when I published this was about 2-3 years ago, but, in last 2-3 years, I became a little bit more [inaudible 00:22:58], because I read more articles about mycobiome. And our mycobiome is equally important as our microbiome. These in our food, molds and mycotoxins in food are really major sources of activation of T-helper 17 and downregulation of Th1, or overactivation of Th1, downregulation of T Reg cells, responsible for induction of autoimmunity.

                                                So, that’s why highly recommend also for patient with autoimmunity, not only are fixing the gut microbiome, you have to try to fix also the mycobiome. We used to talk about Candida albicans in… many, many years ago, I published an article in 1988 that Candida albicans cross-reacted with human tissue, including thyroid. And our friend, mutual friend, with Dr. Cast, and Dr. Rosenblum, Michael Rosenblum, we mentioned his name tonight. So, he was, at that time, treating patient with autoimmunity for Candida albicans, tropicalis, and there are many other molds [inaudible 00:24:39]. So, in my opinion, when they test for urine mycotoxins, those urine mycotoxins are coming from molds and mycotoxins from food, and they are not coming from exposure in the building, at least 80% of them. Let’s go with that. Okay?

Dr. Weitz:                            But are you suggesting that the mycotoxins in food are equally problematic as the mycotoxins-

Dr. Vojdani:                        More.

Dr. Weitz:                            More.

Dr. Vojdani:                        Way more. Based on what I’m reading, now is way, way… you know I published at least 20 different articles about molds and mycyotoxins in different journals, started 25 years ago. But now, today, I’m standing here saying that yeast and molds in the food are significant, very significant induction of autoimmunities, particularly autoimmunity of the gut, including Crohn’s and ulcerative colitis.

Dr. Weitz:                            Yeah.

Dr. Vojdani:                        So, an article, yes, environmental factors continue to change our microbiome and mycobiome. I didn’t put the other slide. You agree with that? Okay? So now we know the environmental factors are changing. And these are some of them. It’s a beautiful slide. It’s in my book. That stress can do that, abnormal gut microbiome, gut microbiota composition. This is about leaky gut now. Okay? We take it one step further. Medications. When we make lots of inflammatory cytokines, undigested food, especially lectins and the glutens, food colorings, and gums, and later on you’ll see the plastic. Plastic, I have a slide for it that is changing the gut microbiome. You’ll see the slide later.

                                                So, when we have disturbed gut microbiome and mycobiome, this is what is going to happen to our tight junctions. Release of lipopolysaccharides, cytolethal distending toxin, and some enzymes, such as enolase, which is involved in many autoimmune diseases, is released by, for example, Candida, all can break down the tight junctions, occludin, zonulin, and so forth. The consequence of that is entry of unwanted large molecules through the submucosa and in circulation. Immune reaction against that now would have 5 different type of antibodies against food, against tight junctions, against lipopolysaccharide, against cytolethal distending toxin, and other antigens. So this is the mechanism, is the consequence of environmental factor effect on our gut microbiome, mycobiome, resulting in some of these autoantibody production.  

                                                So, in 1998, I was working on a test development. That’s one of my specialties, my fun. And I developed this test called intestinal barrier function. In year 2000, I got a patent for it. And it was about measuring antibodies against 5 most common food, eggs, soy, corn, wheat, and milk, gram negative bacteria and gram positive bacteria, aerobic, anaerobic bacteria, and yeasts. If the antibodies were elevated simultaneously against all of these, we said the patient is only then, again, I’m talking about 1998, leaky gut syndrome.  And, as you know, then was just the beginning. Nobody was aware of leaky gut and gut microbiome and all of that. And so, this is a new version of the test, which was started in 2015. So what we do, we measure antibodies against active components that you saw in the slide. The toxins break down the tight junctions and also destroy the epithelial cells. So, actomyosin, or actin, we make antibody against them. Tight junctions are occludin and zonulin. You make antibody against those. Right? And then, lipopolysaccharides produced by the E. coli, Salmonella, Shigella, and Klebsiella, namely.  So, this is one of the best tests that I recommend to order when, for the first time, the patient walking in your office, and you do not know where to start. Not to spend too much money, just this will be the test. And you see, for example, this individual is having antibodies [inaudible 00:30:53] and significant level of IgA antibody, which is much more important, because its origin is from the gut and against lipopolysaccharides. So this individual suffered from gut dysbiosis and leaky gut.

                                           Now, lots of you know Dr. Kharrazian. Okay? Right? And I had the pleasure of working with him for many, many years. In fact, he did his PhD thesis in my lab, actually.

Dr. Weitz:                           Oh.

Dr. Vojdani:                        So, they looked at couple hundred blood samples sent by different doctors to Cyrex Laboratories for this test. Right? For this test. And then, they found some of them, like half of them, for simplicity I’m saying that half of them were positive for leaky gut, the other half completely negative. It’s possible. Right?   Then, the doctors also ordered Array 5, which is Multiple Autoimmune Reactivity, against 24 different tissue antigens. And the tests were done a year or 2, 5 years later, they went and took the data, and analyzed the data. And the findings were unbelievable, that if the individual had leaky gut, the probably of having autoantibody against their own tissue was between 5-30%, 30-fold, from 5 to 30-fold more.  So, I think in one of the magazines, they wrote this article based on that publication, that if you have leaky gut, probability of developing autoimmune disease is 30-fold. So here, when they were negative for leaky gut, [inaudible 00:33:29] level of antibodies against fibrillin, which is involved in rheumatoid arthritis. The same thing arthritic [inaudible 00:33:39]. And the red shows the level of antibodies in individual with leaky gut. And there are 7-8 different slides, and it just shows one, and the same thing are other cell antibodies, ASCA and ANCA. What is ASCA? Anti-Saccharomyces cerevisiae IgA antibodies. That’s a yeast in the food that we should remove it from our diet, whether it’s in beer or in bread. And ANCA is Antineutrophilic cytoplasmic IgA antibodies. So, ASCA is in Crohn’s, ASCA antibodies, ANCA antibodies in ulcerative colitis. When the neutrophils become activated due to some environmental factors, they release these antigens that make ANCA antibody.

                                                So, that was fascinating. So, here in the article they say, when they did logistic regression analysis, there was a 3 to 30-fold increase, so that’s, maybe I said 5-30, but they said 3 to 30-fold increased probability of developing autoimmune disease if you have leaky gut.  And in another study, I did not put the slide in here, but if you do, leaky brain, meaning blood-brain barrier, 70% correlation between… that’s my publication with Dr. Kharrazian in 2020. If a person is making antibodies against components of gut barriers, is going to make also 70% probability of making antibodies against blood-brain barrier proteins.  And so, this test, Heather was talking about in the introduction, I call this, or we call this, the essential barrier panel. I’m not sure if still this is available, Heather, the combination of all 3 I highly recommend it to be done at the same time. So, it is leaky gut, leaky brain. This is for irritable bowel and SIBO. What we are testing is antibodies against bacterial toxins. It’s just more than just irritable bowel syndrome and SIBO. LPS is different antigen, and bacteria cytolethal distending toxin is different antigen produced by a different bacteria. So, I highly recommend this tests.

Dr. Weitz:                            Yeah, I think most people are not aware that SIBO is actually an autoimmune disease.

Speaker 7:                           Yes.

Speaker 3:                           Yeah.

Speaker 7:                           Yes.

Speaker 3:                           Chronic SIBO.

Dr. Vojdani:                        So, these are the major, major panels offered by Cyrex. So, I’m not going to do this, but it is all about environmental factors and their role in induction of inflammation, autoimmunity, and neurodegenerative disorders. Okay?  So, I started with this, saying that the immune system in people is as diverse as height, beauty, intelligence, and other features, and you remember that why 3 people getting the same medication. And that is because there are so many cells in the blood. And by the way, there are receptors on those cells. It’s called CD, cluster differentiation. Today, I believe that we have 350 different cluster differentiation and different type of lymphocytes. But today, clinically, these are the most important ones.

                                                So, in addition, looking at antibodies, for autoimmunities, you have to access the cell-mediated immunity. And this is the most comprehensive way. You look at T-cell; then B-cell; then the ratio CD4/CD8, or helper cytotoxin; their ratio; T-helper 1; T-helper 2; their ratio; regulatory T-cell, which regulate immune system; T-helper 17, protect us against pathogens, but also causing autoimmunity if overactivated, that’s why we look at the ratio of TReg and T17; natural killer cells… Just an article published 2 days ago, in journal called Microorganisms. You can go online and download it, if you’d like, [inaudible 00:39:31] article in Microorganisms about natural killer cell, and you’ll get that.

                                                So, we used to just look only at the first 2, CD56, CD16. Add KT cell. It’s not natural killer cell; it’s T-cell with receptor for natural killer cell, and it’s there first, but these are the new development. CD57, wrongly they used to use that for diagnosis of Lyme’s disease. But how can a natural killer cell could be used for diagnosis of a specific infectious disease? So, they turn around, they were wrong. But, these cells, CD57, is a major cell, fighting virally infected cells and tumor cells, and also, it’s doing immunoregulation, regulating the immune system, because they produce cytokines.

                                                Now, when you combine CD57 with CD16, they become super killers. And guess what? When we get older and older, we get more of the CD57, because, when we develop autoimmune, we become prone to autoimmunity. It seems that the body makes more of these cells in order to prevent autoimmune disease and cancer as well. So these are cells fighting against cancer and autoimmunity. So, that’s why we should have more of them. And then, finally, CD57 joined forces with cytotoxic T-cells, CD8 cell. Also, they become super killer. So all of these are being reviewed in that journal article called “Natural Killer Cell,” Journal of Microorganisms.

                                                So, the complete picture of the immune system only could be discovered if we look at humoral immunity antibodies and cell-mediated immunity. So the antibodies you see there lyse up, plate, we take drop of blood, dilute it, circle around, and then we add in duplicates to the plate coated with an antigen, let’s say lipopolysaccharide. After addition of several reagents, finally color develops. The color, strength of the color, is proportioned to the amount of antibody in the blood of the patient. And so, ELISA reader is going to read that, and we get information, how much antibody that person is making.

                                                So the sample [inaudible 00:42:58] we take another tube of blood. This time is [inaudible 00:43:01]. We take drop of blood. In that drop of blood, there are lots of cells, T-cells, B-cells, Th1, Th2, and so forth. There are monoclonal antibodies against those 350 cluster differentiations available. We add them to that drop of blood, and the cells become red, green, blue, can be different colors. The flow cytometer is going to separate them based on their colors. The computer is going to count them, and then, now we get also assessment of our cell-mediated immunity. So, we take that integrated data between humoral and cell-mediated immunity, and we then, hopefully, you are going to translate that into your practice to take care of your patient. This is the best way to do at the immune system.

                                                Now, environmental factors can effect both humoral and cell-medicated immunity. In fact, cell-mediated immunity are more even sensitive to environmental factors, because, again, antibodies are produced by the cells after all. Right? So, any miscommunication between different cells of the immune system results in abnormal production of antibodies, less antibodies or more antibodies. So foods are one of those, undigested food, and that’s the book that I wrote few years ago. But soon that book is, I had [inaudible 00:44:49] 20 years [inaudible 00:44:49].

                                                So, many years ago, I asked this question, when it came to, for example, if we test so many proteins, like hundreds, why we measure antibody against one only, which is [inaudible 00:45:19] 33 amino acids? So, that became evolution of Array 3, and today, we are measuring antibodies against 12 different proteins, 3 different transglutaminases, and one which is called microbial transglutaminase, or wheat glue, which is everywhere, in the restaurant and everywhere in some different foods that we purchase. So then, around 2008, I asked this question, and I am going to ask Ben. Do you eat raw potato?

Dr. Weitz:                            No.

Dr. Vojdani:                        Do you eat raw beans?

Dr. Weitz:                            No.

Dr. Vojdani:                        Thank you. So why laboratories are doing testing for food sensitivity, which all copy, many years ago, I developed IgG testing in 1986. So, why they measure antibodies against raw potatoes? Do you get the same information if you cooked the potato and measured antibody?

Dr. Weitz:                            It would be different.

Dr. Vojdani:                        Beans especially. Right? If you don’t cook them… Who is the nutritionist in here? What will happen to us if we consume raw beans? The fact that we cook them and we can eat them without [inaudible 00:47:01] change in antigenic structure after cooking. So that also is going to affect the testing. So they, those labs, either giving you a false positive or a false negative results. So, when I developed Array 10 for Cyrex, we testing, if we eat food in the raw form, we measure antibody against raw form of that. If we eat it in the cooked form, we measure antibodies in cooked form. And if we eat it all raw and cooked, then we measure antibody against both of them. And so, that’s how you get the most reliable test results, by testing Array 3, 4, 10, and so forth. Okay?

                                                So that’s, major environmental factor is food that we discuss. And, you’re seeing here that different [inaudible 00:48:11], even gums, gums, they’re everywhere. But you know what is molecular size of the gum? Lipopolysaccharides, for example, is the antigen produced by E. Coli, Salmonella. What is the size? 65,000. Like albumin. Albumin in our blood is about 60,000. Gums are 5 million. Okay? So, they thought they’re going to be in and out, that’s why they add it to everything, but in reality, we are going to digest them to smaller molecules, like 5 million becomes 8 or 10 times 50,000, or 100 times of that, and then, we react against them, and we make antibodies.

                                                [inaudible 00:49:13] are proteins found in the oils. Nobody’s testing any of this [inaudible 00:49:19]. And, of course, lectins and glutamines that contribute so much to autoimmune disease, for example, in one of our publications, we found that [inaudible 00:49:39] glutamine cross-react with thyroid peroxidase. So, definitely, patient with thyroid autoimmunity will have to remove lectins of the glutamine from their diet. So that was [inaudible 00:49:49].

                                                Now, toxic chemicals. Just look at this slide. Definitely, toxic chemicals, when they get into digestive tract, can change the integrity of the gut, can change our microbiome, can change our mycobiome, and therefore cause permeability problems. And chemicals, by themself, do not challenge the immune system directly, but when they bind to human tissue, for example, if we take some heavy metals, [inaudible 00:50:38] those heavy metals rebind to hemoglobin or albumin, and now, our immune system is going to attack the combination of heavy metals with hemoglobin or albumin. And now, this kind of autoimmunity against our own proteins. So that’s the mechanism. We call, the terminology for that is neoantigen formation, or new antigen formation, the chemicals bind to human tissue proteins.

                                                Now, I would like to… back to this issue. It was in the news [inaudible 00:51:31]. Okay? Hundred times more tiny pieces of plastic that was previously estimated. This was on the news almost 10 days ago.

Dr. Weitz:                            Yeah.

Dr. Vojdani:                        Right? Right. And then, I think it was sort of [inaudible 00:51:48], and then, the guy added something, said, “But we don’t know really what is the clinical effect of these particles.” So he completely destroyed the views, because it is against the industry. They had to say something about it. Now, I was lucky enough, the next day, I read this article in Journal of Molecular Science, “Polystyrene Microplastics Exacerbate Candida Albicans Infection Ability In Vitro and In Vivo.” so here, the best evidence that toxic chemicals [inaudible 00:52:50], competing with our hormones, can change our gut mycobiome.  So these are some of the antibodies that, at Cyrex, we are measuring against these chemicals for neoantigen with human tissue. And you see, bisphenol A, bisphenol binding protein, tetrabromobisphenol A, tetrachloroethylene, and then, cosmetics parabens, heavy metals. So, this is about contribution of toxic chemicals to autoimmunity. Pathogens.

                                                These are the 3 amigos, right? And so, SARS-CoV-2, I published, by now, 10 different articles about contribution of SARS-CoV-2 to autoimmunity to international groups, including Professor [inaudible 00:54:05], who organizes the International Conference of Autoimmunity, which, this May, is going to be in Slovenia. But, we knew already about Epstein-Barr virus and HHV-6 for more than 30 years. These viruses are responsible for development of many autoimmune diseases. An example of Epstein-Barr virus [inaudible 00:54:38] rheumatoid arthritis, multiple sclerosis. Same thing for for HHV-6, and now we know SARS-CoV-2 is doing the same.   So, in the case of long COVID, it is not just SARS-CoV-2. SARS-CoV-2 infection causing reactivation of latent viruses, EVB and HHV-6, and therefore, viral persistence, resulting in inflammation and autoimmunity. How are we doing with time?

                                                So that’s why we test against 29 different pathogens, part of there are only 12, which share [inaudible 00:55:41] with human tissue. Every single item that you see in here, including oral pathogens, which are the first two, [inaudible 00:55:53], they have special group of amino acids, peptides, which share [inaudible 00:56:03] with human tissue, and antibody against them may contribute to autoimmune diseases.

                                                So, here’s some example of looking at Epstein-Barr virus, cytomegalovirus, and at least one and two herpes viruses. This patient is having reactivation of Epstein-Barr. Why? Because every antigen is positive. Under normal condition, that is absolutely negative. Make IgM antibody against cytomegalovirus, so there is ongoing infection with cytomegalovirus. And look at herpes 5, 6, at the highest level. So, one nation, 3 different viruses, and this patient most probably was in the process of developing autoimmune disease if it was not going to be treated for these 3 viruses. This is one of the articles that, [inaudible 00:57:18] article I published in January 2021, when we took [inaudible 00:57:28] antibodies made against SARS-CoV-2 spike proteins [inaudible 00:57:34], and added that to about 70 or 80 different tissue antigens that I have in my lab, and found that about 25 of them became highly positive. That was the best truth that SARS-CoV-2 [inaudible 00:57:59] contributes to autoimmunity. That article by now was viewed by more than 200,000 scientists. Most of my articles got to 10,000, 20,000, but this one, 200,000.

                                                So that is contribution of SARS-CoV-2 to autoimmune. So, I already gave you some introduction about contribution of SARS-CoV-2, EBV, and HHV-6, that, together, contributing to the inflammation and autoimmunity. This article, you can download it from journal called Viruses. And, in relation to long COVID, yes, the viral persistence reactivation of EBV, HHV-6, release of super antigens, changes our gut microbiota, and change or effect on the immune system, all together [inaudible 00:59:15] in multi-tissue autoimmunity. And that’s why this is one of the tests that I developed for Immunosciences Lab for long COVID, which is a blood test. We measure antibodies against SARS-CoV-2, EBV, and HHV-6. And another version of that also, we measure also autoimmune panel as well. But, combination with other tests, like leaky gut and L MAP by Cyrex is going to make the picture more [inaudible 00:59:43].

                                                Okay? And here, you see the example of an article that autoimmunity is the whole work of post-COVID, many patient with long COVID, they develop autoimmunities. And you see the percentages. In fact, they call that polyautoimmunity, not only one autoimmunity, different autoimmunities. So, testing for long COVID and this overlap within myalgic encephalomyelitis and chronic fatigue syndrome I summarize it right here, that the SARS-CoV-2 antibodies [inaudible 01:00:37] Immunosciences Lab, EBV, HHV-6 Immunosciences Lab, lymphocyte [inaudible 01:00:37] Cyrex, antigenic [inaudible 01:00:41] Cyrex, and the biomarkers of autoimmunity that autoimmune panel, which is right here, [inaudible 01:00:51] that we do at Immunosciences Lab.

                                                And here, example of a patient, positive for SARS-CoV-2, positive for HHV-6, positive for EBV, [inaudible 01:01:06], and [inaudible 01:01:09] antigens. So this patient should be treated for EBV and HHV-6 in order to prevent autoimmune disease for this individual with long COVID. And indeed, when we did the autoimmune panel, please look, ANA was negative, but [inaudible 01:01:30] was, although it’s not very high, but that is the beginning of autoimmunity. The same thing rheumatoid factor. The same thing [inaudible 01:01:44]. And the same thing for anti-actin antibody. So this individual was in the process of developing autoimmunity due to EBV, CMV, and HHV-6.   And just to take something home, different treatments based on different articles that I read in scientific journals, including [inaudible 01:02:24] low-dose hydroxychloroquine and azithromycin. And then some even had [inaudible 01:02:33] this publication. All of these, anyway, please, if you want to take a picture, take this home with you. So that’s the message.

                                                Then, finally, a couple slides that tie everything together, how unhealthy lifestyle can lead to inflammation in the brain. So, fire in the gut break down the gut barriers, and the [inaudible 01:03:12] breaking the blood-brain barriers, now inflammation is the brain, resulting in multiple autoimmunity, including autoimmunity in the brain.

                                                So with that, I would like to read something for you, and then present only 2 or 3 slides on this article. So, my friend, Dr. Weitz, says that, “Those who think they have no time for healthy eating will sooner or later have to find time for illness.” So please pay attention to the title of this article, “How to Diet: A Lifestyle Improved the Gut Microbiota and Helped Combat Fungal Infection,” which is also part of the gut microbiome.

                                                And beautiful pictures right here. Okay? Unhealthy diet contributing to inflammatory pathogenesis and [inaudible 01:04:31]. So look at all of this. Alcohol, unhealthy lifestyle, antibiotics, chronic stress all together affects the gut barriers, the blood-brain barriers, the immune system, humoral immunity, cell-mediated immunity. That’s what. The second, look please at these options. [inaudible 01:05:01] defect of a diet high in vegetables, fiber, vitamins, micronutrients, omega 3 fatty acids, probiotics, prebiotics on the gut microbiota. I think the picture is beautiful.

                                                And finally, the last slide. Okay? So, again, these are all antifungals, so the emphasis now is not just on microbiome, but mycobiome. And these are some which are good for preventing [inaudible 01:05:46] of the microbiome. I’m not going to read all of that, just look at the picture and please take some of these pictures with you and share with your patients. And you can download this article in the same journal, Microorganisms, that they published my article 2 days ago about natural killer cell.  Thank you so much, and I hope you enjoyed the presentation.

Dr. Weitz:                            Would you give us an example of a patient who, say, has tested positive for leaky gut and tests positive, say, for infections or toxins, how the lymphocyte MAP test helps us to manage that patient?

Dr. Vojdani:                        Thank you. Okay. In early 90’s, I was dealing with many, many patients who had history of exposure to different toxic chemicals, example, people who were working for [inaudible 01:06:58] became sick because, at the end of the day, they were washing their hands and their body with solvents to get rid of grease and all kind of things that they used for cleaning, and they developed immune responder. And when we tested their blood, we found that about 30% of them, you remember the 3 babies, the 3 individuals? 30% were on this side, hyperactivation of the immune system, 10% hypoactivation, and then, in the middle, of course, were some that were okay, because we have different immune print.  How did we do that? We found then, based on looking at CD4/CD8 ratio, T-cell, B-cell, CD4/CD8, elevation in CD4/CD8 is indication of inflammation and autoimmunity. And reduction in CD4/CD8 ratio below 1.5, especially 1.0, is indication of immune deficiency, just with that knowledge, CD4/CD8. And then we used to call that chemical-induced AIDS. Yes, everybody was thinking about AIDS, virus, virus, but here, chemicals can do the same thing. So, lymphocyte MAP then was very helpful to us.

                                                But today, because we are looking at Th1, Th2, for example, yesterday, I presented a case about… for a second, mast cell activation syndrome. Okay? How can we detect that? By looking at Th2. The patient had very high Th2 and low TReg. And also, looking at Th1 and Th2, and TReg, Th17, low TReg, high Th17, high Th1, that’s the finger prick of autoimmunity as well.  And then natural killer cells, [inaudible 01:09:31] where the body is calling more soldiers to fight, either the patient’s having viral infection, bacterial infection, parasitic infection, or cancer. I’m talking about, let’s say, NK cells are 50%. Now, you find in one of them 50%, 40% of the cells became natural killer cells. When 40-50% become natural killer cells, the number of T-cells become much lower, the number of B-cells become lower. And so, complete immune dysregulation. We have absolute fingerprints, [inaudible 01:10:24] print, based on L MAP.

                                                And so therefore, for a patient walking for the first time in your office, if you want to spend the buck the most efficient way of spending the money is to order Array 2 and L MAP, and if you want help with interpretation of results, either you call Dr. Sasha, which his wife is here, or you call me, and I’ll be very happy to help you in interpretation of test results. I’m just looking because Cyrex has 3 or 4 different clinical consultants, but some of you like to call me, and I appreciate it.

Dr. Weitz:                            And are there any actual strategies, supplements, et cetera that can accentuate findings on the [inaudible 01:11:18] to-

Dr. Vojdani:                        Yes, yes, yes, yes. Maybe for now, could we just think about nutritional immunology for next year?

Dr. Weitz:                            Okay.

Dr. Vojdani:                        Okay? There is a chapter, again in the [inaudible 01:11:36] Immunology, it’s called, “What is the Immuno [inaudible 01:11:41],” very sophisticated, but the one I like the most is nutritional immunology, based on hundreds of articles that I’ve collected. For example, for regulatory T-cells, we made these flowers with a kind of, for example, for TReg cells, which is regulation of the immune system. It’s got vitamin A, vitamin D, vitamin C. Why there are receptors, and TReg has a membrane for those. Then, [inaudible 01:12:22] vegetables. [inaudible 01:12:26], cabbage, broccoli, all of those, also have receptor on their surface, [inaudible 01:12:38]. Finally, acetate, butyrate, and propionate. And I think there are amino acids, which is in [inaudible 01:12:54].

Dr. Weitz:                            [inaudible 01:12:54].

Dr. Vojdani:                        Yeah. [inaudible 01:13:00] also binds to certain receptor of TReg cell. So here is example of flowers with petals for TReg cell. We have the same thing for Th1, Th2, Th17, and so forth. I think you have a copy of, right?

Dr. Weitz:                            Yes, I think from last year or the year before, right?

Dr. Vojdani:                        Yeah, yes. But if I will have more time, I’ll have to improve that based on more articles. Like last week, another article came up that, if you do [inaudible 01:13:35] juice from red cabbage, then you give it to your patients with Crohn’s, they improve significantly. What do you think? How does it work? It’s going to act to regulate the TReg cells. That’s the mechanism. Okay?

                                                Yes, please.

Speaker 7:                           How do [inaudible 01:14:07] ozone for [inaudible 01:14:09] autoimmune?

Dr. Vojdani:                        I honestly don’t know, because there is no solid research about ozone. I don’t know there’s more studies, for example, but I might have missed it. [inaudible 01:14:23] I publish 4 different articles 15 years ago. 20 years ago, I was working with [inaudible 01:14:31], and we gave 5,000 mg of oral vitamin C for a group of athletes, and we collected blood and urine. We tested the natural killer cytotoxic activity. 24 hours later, the majority of the NK cytotoxic activity went up from 3 to 10-fold. And after 48 hours, it went back to normal, meaning you have to take it every day in order to maintain healthy natural killer cells. But for ozones, unfortunately, we don’t have similar research projects or articles available.   Okay? So, we have to leave, right?

Dr. Weitz:                            Yeah. It is closing. We have time for a few more questions, so, if anybody has questions.

Speaker 8:                           [inaudible 01:15:42] dose matters, but these ingredients [inaudible 01:15:46], they’re enough to kill [inaudible 01:15:50] mold. So, according to this slide, these ingredients will not treat [inaudible 01:16:11]. Did I understand that correctly?

Dr. Vojdani:                        Yes.

Speaker 8:                           So-

Dr. Vojdani:                        Well, I think all these products is effective with immune function in the gut, and improved immune function in the gut is going to fight the microbiome and the mycobiome.

Speaker 8:                           Are you familiar with at what dose, for example, how much [inaudible 01:16:44] you would need in order to make a difference on living yeast in the mycobiome?

Dr. Vojdani:                        No, I don’t know the exact amount.

Speaker 8:                           Yeah.

Dr. Vojdani:                        Good question. Maybe we should do that article [inaudible 01:16:57].

Speaker 8:                           It’s impressive.

Dr. Vojdani:                        [inaudible 01:17:01].

Dr. Weitz:                            There are nutritional products on the market that have extracts from coconut oil that are known to have the antifungal properties.

Speaker 8:                           So, [inaudible 01:17:11] saying you’re not supposed to take coconut oil because it will kill healthy bacteria in the gut, because it’s-

Dr. Weitz:                            Who’s saying that?

Speaker 8:                           [inaudible 01:17:20] in one of his autoimmune… so, ingesting-

Dr. Weitz:                            That’s kind of an ongoing debate-

Speaker 8:                           Exactly, exactly.

Dr. Vojdani:                        Was it based on an article of recent? Because-

Speaker 8:                           It was based on, it might have not been him. I do remember him saying you shouldn’t take it [inaudible 01:17:40] unless you’re [inaudible 01:17:44]. But the coconut oil thing is, depending on who you ask, they’re going to say something different, so I was wondering if there was dosing you were familiar with [inaudible 01:17:58] that dose makes a difference.

Dr. Vojdani:                        Please.

Speaker 9:                           I noticed you have tests for lectins, but are you testing in [inaudible 01:18:11] acid? Is that anything that’s come on your radar?

Dr. Vojdani:                        No, no, no. I know of one of the [inaudible 01:18:18] was talking about a stomach acid.

Speaker 9:                           Because they think that [inaudible 01:18:23] seems to be affecting joints, and there’s been a fair amount of weird small group interest in that, but I’m beginning to see some promise in finding out more about it.

Dr. Vojdani:                        Okay. I don’t know how we can measure that.

Speaker 9:                           It’s hard.

Dr. Vojdani:                        Because it’s not easy.

Speaker 10:                         Oxalates.

Speaker 9:                           Oxalates?

Speaker 10:                         Yeah, you can measure them. Organic acid urine test shows oxalates.

Speaker 9:                           Okay. So that would also show urine-

Dr. Vojdani:                        Yeah, but where are they coming from?

Speaker 10:                         Plants.

Dr. Vojdani:                        Okay.

Speaker 10:                         Everything.

Dr. Vojdani:                        Okay. So because, recently I read this article about organic acids and organic acids in the urine, all the claims that the [inaudible 01:19:08] are making [inaudible 01:19:08].

Speaker 9:                           [inaudible 01:19:08].

Dr. Vojdani:                        Excellent questions.

Speaker 9:                           [inaudible 01:19:08].

Dr. Vojdani:                        Sorry.

Speaker 9:                           Were there… okay. But, I’m interested, I want to hear about that next year. Okay.

Dr. Vojdani:                        Okay. Thank you so much.

Speaker 9:                           Thank you.

Dr. Vojdani:                        [inaudible 01:19:32].

Dr. Weitz:                            Thank you everybody. See you next one.

 


 

Thank you for making it all the way through this episode of the Rational Wellness Podcast. For those of you who enjoy listening to the Rational Wellness Podcast, I would certainly appreciate it if you could go to Apple Podcasts or Spotify and give us a 5 star rating and review, that way, more people will discover the Rational Wellness Podcast.  And I wanted to let everybody know that I do have some openings for new patients, so I can see you for a functional medicine consultation for a specific health issues, like gut problems, autoimmune diseases, cardiometabolic conditions, or for an executive health screening, and to help you promote longevity and take a deeper dive into some of those factors that can lead to chronic diseases along the way. And that usually means we’re going to do some more detailed lab work, stool testing, sometimes urine testing, and we’re going to look at a lot more details to get a better picture of your overall health from a preventative functional medicine perspective. So, if you’re interested, please call my Santa Monica Weitz Sports Chiropractic and Nutrition Office at 310-395-3111, and we can set you up for a new consultation for functional medicine. I’ll talk to everybody next week.

 

Dr. Howard Elkin and Dr. Ben Weitz discuss Rhabdomyolysis.

[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

2:17  Rhabdomyolysis (rhabdo) is characterized by an acute destruction of muscle tissue and the contents of the destroyed muscle tissue–myoglobin–is emptied into the bloodstream.  This myoglobin makes the urine appear brown in color and thick and it can overwhelm the kidneys and cause kidney destruction and renal failure.  75% of the time such patients are men over the age of 30 and dehydration and certain medications can increase the incidence.  From 2005 to 2015 there has been a 12 fold increase in rhabdomyolysis in the US and this is largely related to the trend towards high intensity workouts at bootcamps and Crossfit and other High Intensity Training gyms like Orange Theory that often attract people who have not been exercising and some of whom end up overdoing it in such class type situations. 

6:24  Certain drugs like statins that are used to lower cholesterol can play a role in causing rhabdo, since they can adversely affect skeletal muscles, though this is more common in the older statins that are lipophilic like simvastatin (Zocor) and atorvastatin (Lipitor) than the newer statins that are hydrophilic like fluvastatin, rosuvastatin (Crestor), and pravastatin.  This can be made worse if certain other drugs are taken at the same time that inhibit the cytochrome p450-3A4 liver detox pathway, such as certain antibiotics (such as clarithromycin), antifungals, calcium channel blockers and certain other drugs.  Also, the use of alcohol, amphetamines, and methamphetamines can worsen the likelihood of the occurrence of rhabdo. 

8:34  Patients with rhabdo usually present with intense pain, extreme fatigue, and their urine is very dark, even brown, because of myoglobin that is being released.  They will have elevated CPK in their blood as well as elevated myoglobin.  It should also be pointed out that bodybuilders may have modest elevations of their CPK due to weight training and breaking down muscle tissue. Normal CPK is between 20 and 120 and bodybuilders may have CPK up to 500, while some rhabdo patients may present with a CPK of 10,000 or 100,000 or even higher. 

12:09  While anabolic steroids can be damaging to health and are likely responsible for the deaths of quite a number of bodybuilders, they are not likely contributing to rhabdo despite claims made in some of the scientific papers published about rhabdo.  Rhabdo involves a state of extreme breakdown of muscle or catabolism, while anabolic steroid are anabolic and they promote muscle recovery and muscle building.  On the other hand, many patients take corticosteroids for inflammation, extreme infections, asthma, etc. and these are catabolic and could contribute to rhabdo. 

14:47  Steps to avoid rhabdo include all the things you would do to avoid overtraining.

           

 

Dr. Weitz:            Right. Now, what are some of the steps that bodybuilders and fitness enthusiasts can do to avoid rhabdo? Well, since this is a form of extreme over-training, we need to do all the things you would do to avoid over-training. So that means if you’re just starting to engage in a new form of exercise, maybe you were a runner, now you’re going into weight training, or vice versa, if you’re just starting a CrossFit program, maybe you haven’t been exercising very much, or maybe you took a break from exercising, you need to gradually ramp up your intensity, your duration, and the frequency of your exercise. In other words, let’s say you took six months off from training and now you’re going to start training for an hour a day in a high intensity class, five, six days a week, you’re probably asking for trouble. So start out every few days, slowly increase your intensity.

                                Now, that’s one of the problems with some of these classes is you can’t start off at your own pace. So you’re probably better off starting out in a gym by yourself slowly increasing the duration and intensity of your exercise. You jump into a class an hour class, everybody’s at a high level already, that’s one of the problems that can happen. Also, avoiding exercise in extreme heat. So don’t run a marathon in the summer in Arizona. High heat conditions, not being properly hydrated, not having a proper balance of electrolytes is another thing that can increase your potential for having rhabdomyolysis. It’s also important that you make sure that you’re sufficiently recovered from your workouts. So you’re into a new workout program and you feel like you can handle it because you’ve been working out and now maybe you’re on day three, four or five and you can barely get out of bed.

                                Your body’s telling you you probably are starting to be overtrained, and that’s something you want to avoid. There’s also something called heart rate variability, which we want to discuss in another talk, but that’s a sign when your heart rate variability decreases that you’re overtraining. Also, when you’re working out, you need to make sure that you’re consuming sufficient amounts of protein, carbohydrates, and calories to help you recover from your workouts as well as getting good quality sleep. So if you’re in a situation where you’re traveling where you haven’t been able to sleep, you’re suffering work or relationship stress, or maybe you’re doing extreme dieting like a competition bodybuilder, getting ready for a competition, and let’s say in addition to working out six days a week with heavy weights, now you’re doing large amounts of cardio. Maybe you’re doing an hour or two hours of cardio a day, you’re also practicing your posing and you’re doing an extreme diet.

                                That’s something you’ve got to be careful about. That might put you in a situation where you could end up with rhabdo, especially if you’re also taking stimulants. And we know that people exercise sometimes take stimulants before they work out, like with pre-workout drinks or they have these energy drinks. Those can have large amounts of caffeine and they can have multiple forms of stimulants, so they could have caffeine. They could also have other herbal stimulants that combined with caffeine could end up being a large amount of stimulant.

                                I think having a cup of coffee or a cup of green tea or something like that is probably fine, but I would recommend for the most part, avoiding most of these energy drinks that are out there. And of course, people who are going for competition, like some of these bodybuilders and fitness people, they sometimes take stimulants to help them reduce their body fat, to reduce their appetite. So the one popular stimulant is called clenbuterol, which is sort of an asthma medication, but it also reduces appetite and is used by fitness and bodybuilding people to help get lean for bodybuilding shows. And that’s something that puts you at risk.



Dr. Howard Elkin is an Integrative Cardiologist with offices in Whittier and in Santa Monica, California and he has been in practice since 1986.  While Dr. Elkin does utilize medications and he performs angioplasty and stent placement and other surgical procedures, his focus in his practice is employing natural strategies for helping patients, including recommendations for diet, lifestyle changes, and targeted nutritional supplements to improve their condition.  Dr. Elkin has written an excellent new book, From Both Sides of the Table: When Doctor Becomes Patient.  His website is Heartwise.com and his office number is 562-945-3753.

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

 



 

Podcast Transcript

Dr. Weitz:            Hello, Rational Wellness podcasters. I’m here today with my friend, integrative cardiologist, Dr. Howard Elkin, and our goal is to comment on a potentially very serious condition, rhabdomyolysis, that’s been in the bodybuilding news recently. We will explain what this condition is, what causes it. We will try to clarify what types of drugs may play a role in it and what we can do to avoid it. To make our lives easier today, we will refer to rhabdomyolysis henceforth in this discussion as rhabdo. While rhabdo is not super common, there are 26,000 reported cases per year in the US and this can be a potentially life-threatening condition. There’ve been a number of commentators on YouTube recently discussing rhabdo who are not medical professionals, including some popular YouTubers in the bodybuilding world who generally do an excellent job providing accurate information, but they may not have provided the most accurate advice about this condition.   We thought it was important for two doctors who have both competed as bodybuilders to weigh into this discussion to provide a more nuanced discussion of rhabdo. Our goals are to help you understand what is rhabdo, what causes it, and how to prevent it. We also wanted to clarify which medications might play a role and which medications likely do not, despite what some commentators have claimed. And you can expect Dr. Elkin and I to be commenting about a number of other topics in the fitness and bodybuilding world in the coming months. Dr. Howard Elkin is an integrative cardiologist, and myself, Dr. Ben Weitz, I’m a sports chiropractor and functional medicine practitioner. We both have been practicing doctors for decades and we both have experience competing in bodybuilding in our past. So we feel that we can bring both medical understanding and bodybuilding insights to contribute to this type of discussion. So welcome Dr. Elkin, and why don’t you start us off by explaining what is rhabdo, how is it diagnosed, what causes it?

Dr. Elkin:              Hey, good morning Ben. Thank you so much for inviting me. This is a topic that’s dear to me. So rhabdo, I believe it means to break down or break up, and myolysis is muscle tissue. So this really, this condition is characterized by an acute destruction of muscle tissue and what happens, the contents of the destroyed muscle tissue is actually emptied into the bloodstream. So you’ve got muscle fiber contents like certain metabolites like potassium, phosphorus, and urea, but more important, you have a release of the actual contents of the muscle itself called myoglobin, and along with something called CPK or creatinine, creatine phosphokinase. So it’s the myoglobin that does the damage. And once this is released into the bloodstream, it goes to the kidney and it overwhelms the kidney. It actually can destruct some of the kidney tubules. So the major issue or morbidity or mortality is acute renal failure, which is not insignificant.

                                I think what I’ve read anywhere from 10 to like 40%, that’s a pretty big, it’s huge. So it can potentially very serious situation. Now, like Ben says over, it’s not common, but it certainly isn’t rare. Over 20,000 people in this country have developed rhabdomyolysis yearly, but this is important. This has been a 12 fold increase rhabdomyolysis from 2005, 2015, which is pretty huge, and we think, from what I can gather, it’s the high intensity workouts that people were now doing. The bootcamps and the CrossFit and the Orange Theory and what happens, these are basically group classes and they attract people that are fitness enthusiasts that a lot of them are novices. They don’t really have the background, they haven’t really trained their muscles, so they’re getting into a pretty intense program in a very short period of time. Now, I would like to read how things developed.

                                So we didn’t really know much about this until the ’40s. It was really described as a crush syndrome because it was observed in British people during the blitz in the ’40s in World War II. And what happened, there were crush injuries and people were brought to the hospital and whatever they did back then, they didn’t do a lot. They didn’t have dialysis, but then they would go home and they would die a few days later of renal failure. They didn’t have dialysis back then, so it was kind of called the crush syndrome until they changed the name to rhabdomyolysis. Now, this is very important. About 47% of patients that develop this are engaged in vigorous exercise. So it’s more seen, but you can see it in lots of different situations as well, which I’ll mention. But again, it’s almost half of the people that developed the syndrome or engaged in various exercise.

                                Now, and here’s another thing, 75% are males, 75%, and generally less than the age of 40. So that tells you something. Men tend to be more, I guess they engage in more hazardous activities. And this [inaudible 00:05:46] that I also read. 30% develop on the same day of the exercise, but 55% within 48 hours. So it’s acute and subacute. It can happen immediately or it can happen up to 48 hours afterwards. It’s really not commonly seen in elite athletes because their muscles are more refined, or in the totally untrained muscles because they can’t handle the workout. But it’s this big gap in between and these fitness enthusiasts that are engaged in these activities. So it’s usually male non-elite regular exercisers over the age of 30, and it increases the incident, increases in the situations of dehydration, certain drugs that we’ll talk about in a second.

                                And I’m a cardiologist, so I use statins a lot in my practice, especially in those that have a history of heart disease. But statins are metabolized by a certain process in the liver called the cytochrome P450 system. And certain drugs like this and certain antifungal medications and certain anti-psychotic medications can actually, they’re metabolized by the liver in this particular system, and this can make it more prone to develop this syndrome. I don’t see it as much in my practice now because this is the old generation of statins that like the lovastatin, which is the first one that came out in the mid-80s, actually about ’84, ’85, I was a fellow. And then Simvastatin, which is commonly known as Zocor, but I mentioned Zocor specifically because that was one that is metabolized by the cytochrome P450 system, and that was the statin of choice before Lipitor came out in the late ’90s. And all these studies on secondary prevention and the use of statins with the use of Zocor. So you still see some people on it, I haven’t prescribed it in years.

Dr. Weitz:            So essentially these older statins are fat soluble versus the newer water-soluble statins.

Dr. Elkin:             Correct.  Right.  So the most protective ones would be Pravastatin, which actually was used early on.  It was never really, it didn’t achieve a lot of popularity because it wasn’t nearly as effective as some of the other ones.  But Rosuvastatin, commonly known as Crestor, is a water soluble statin that I personally use for my patients, and it’s relatively safe, but it’s good to know these things.  And also the worst offenders are things like alcohol use, which is very dehydrating, and amphetamine and methamphetamine use, which is very dehydrating, also stimulates the heart. So there’s a myriad of situations that can make this whole situation worse.

Dr. Weitz:            By the way, Howard, when somebody presents with rhabdo, what are the presenting symptoms? What does this picture look like?

Dr. Elkin:              Okay, usually we’re talking, this is not a little bit of muscle soreness that you get from exercising, which is a different situation. Usually it’s intense pain, intense pain in the area that’s involved swelling, but it’s pain, fatigue, extreme fatigue. And also the urine turns very dark because of the myoglobin. And so we’re talking like dark, like brown or very dark yellow. It is not normal urine. So that’s how they present. They have symptoms, it’s not asymptomatic. They have urine that is discolored. And also there’s a test you can do, CPK, which stands for creatinine phosphokinase, is an enzyme in muscle that’s released during heavy vigorous muscle muscular activity and also with rhabdo, but it’s not the thing you want to look for.  Because bodybuilders, I mean, I’ve had an elevation in CPK before, so it can last a couple of days or so after vigorous workout. So that is a muscle enzyme that isn’t the one we’re really concerned with. What you want to measure is myoglobin. Myoglobin is actually the protein that makes muscles work, and that’s released with this acute destruction of the muscle fibers, and that’s what you pick up and not just in the blood, but also in the urine. So it’s microalbuminuria and myoglobinuria. Those are the two main lab tests. So it’s really-

Dr. Weitz:            The other thing I’d like to point out on the CPK is while bodybuilders, so let’s say a normal CPK, depending upon the lab, the range might be between 20 or 40 and 120 or 150 or somewhere in that range, maybe up to 200, bodybuilders who are working out really intensely who are breaking down a lot of muscle tissue might see, especially after a workout or for a period after the workout, might see an elevation of their CPK up to 500, maybe even up to 1,000. But some of these patients with rhabdo present with CPK levels of 10,000, 100,000, and even higher. At that point, we know we’re dealing with rhabdo, and it’s not just a result of working out,

Dr. Elkin:              Right. That’s very important distinction. I mean, you can look at it like this. When we exercise intensely, you may get some muscle soreness a day or two later that’s called DOMS delayed onset muscle soreness. Now, some people say that could be a very mild case of rhabdo, and it’s important to bring this out because how you grow in both its strength and muscle mass is you break the muscle down when you exercise, then it has to rebuild. So there is a little bit of muscle destruction that takes place with a vigorous workout, but not to the extent that we’re talking about.

Dr. Weitz:            Yeah, you’re basically talking about some level of maybe over-training. And that’s something we want to comment about in a future talk is describe exactly what over-training is, how you can monitor it with heart rate variability, et cetera.  But this is a really extreme form of over-training, an acute situation.

Dr. Elkin:              Right. So let me ask you now, Ben, now that we know what this syndrome is and how it’s diagnosed, how do we prevent it?

Dr. Weitz:            Okay, well, first of all, I want to make a comment about one of the types of drugs that is often attributed as being a cause of rhabdo. And I’ve seen a number of reports, scientific reports in the literature where the doctor who writes a report blames anabolic steroids on being the cause of rhabdo. And while I don’t defend anabolic steroids, and we have certainly seen our share of anabolic steroid health problems and death among bodybuilders, and of course, you and I previously commented in a YouTube video that we call dead bodybuilders about all the bodybuilders who’ve suffered cardiovascular and renal and liver problems from anabolic steroids.  This is one case where I don’t think that anabolic steroids properly play a role. Because in rhabdo, you’re getting an extreme breakdown of muscle tissue and anabolic steroids are anabolic, not catabolic. They’re building up muscle, they’re helping recovery, not breaking it down. On the other hand, if the person is taking a steroid known as a corticosteroid, like prednisone, for a number of conditions, including inflammation or extreme infections, et cetera, certain autoimmune diseases, that could contribute to rhabdo, but we don’t think that anabolic steroids can.

Dr. Elkin:              So remember, anabolic means to build, catabolic means to break down, and a lot of people take corticosteroids. They’re used all the time and they have distinct benefits, but they have some major drawbacks, and this is one of them. But I think you’re right, steroids have been blamed for everything. Okay, you name it, and oftentimes unfairly so. But again, we’re not condoning the use of steroids, but we don’t want you to walk by saying, “Oh, this is another thing with steroids.” It’s not true. Again, most of these exercisers weren’t professional bodybuilders. We know of one that is, but it’s these vigorous, so in other words, it’s not elite athletes or elite bodybuilders, but that’s an important distinction. So let’s not blame this particular syndrome on steroid use.

Dr. Weitz:            Right. Now, what are some of the steps that bodybuilders and fitness enthusiasts can do to avoid rhabdo? Well, since this is a form of extreme over-training, we need to do all the things you would do to avoid over-training. So that means if you’re just starting to engage in a new form of exercise, maybe you were a runner, now you’re going into weight training, or vice versa, if you’re just starting a CrossFit program, maybe you haven’t been exercising very much, or maybe you took a break from exercising, you need to gradually ramp up your intensity, your duration, and the frequency of your exercise. In other words, let’s say you took six months off from training and now you’re going to start training for an hour a day in a high intensity class, five, six days a week, you’re probably asking for trouble. So start out every few days, slowly increase your intensity.

                                Now, that’s one of the problems with some of these classes is you can’t start off at your own pace. So you’re probably better off starting out in a gym by yourself slowly increasing the duration and intensity of your exercise. You jump into a class an hour class, everybody’s at a high level already, that’s one of the problems that can happen. Also, avoiding exercise in extreme heat. So don’t run a marathon in the summer in Arizona. High heat conditions, not being properly hydrated, not having a proper balance of electrolytes is another thing that can increase your potential for having rhabdomyolysis. It’s also important that you make sure that you’re sufficiently recovered from your workouts. So you’re into a new workout program and you feel like you can handle it because you’ve been working out and now maybe you’re on day three, four or five and you can barely get out of bed.

                                Your body’s telling you you probably are starting to be overtrained, and that’s something you want to avoid. There’s also something called heart rate variability, which we want to discuss in another talk, but that’s a sign when your heart rate variability decreases that you’re overtraining. Also, when you’re working out, you need to make sure that you’re consuming sufficient amounts of protein, carbohydrates, and calories to help you recover from your workouts as well as getting good quality sleep. So if you’re in a situation where you’re traveling where you haven’t been able to sleep, you’re suffering work or relationship stress, or maybe you’re doing extreme dieting like a competition bodybuilder, getting ready for a competition, and let’s say in addition to working out six days a week with heavy weights, now you’re doing large amounts of cardio. Maybe you’re doing an hour or two hours of cardio a day, you’re also practicing your posing and you’re doing an extreme diet.

                                That’s something you’ve got to be careful about. That might put you in a situation where you could end up with rhabdo, especially if you’re also taking stimulants. And we know that people exercise sometimes take stimulants before they work out, like with pre-workout drinks or they have these energy drinks. Those can have large amounts of caffeine and they can have multiple forms of stimulants, so they could have caffeine. They could also have other herbal stimulants that combined with caffeine could end up being a large amount of stimulant.

                                I think having a cup of coffee or a cup of green tea or something like that is probably fine, but I would recommend for the most part, avoiding most of these energy drinks that are out there. And of course, people who are going for competition, like some of these bodybuilders and fitness people, they sometimes take stimulants to help them reduce their body fat, to reduce their appetite. So the one popular stimulant is called clenbuterol, which is sort of an asthma medication, but it also reduces appetite and is used by fitness and bodybuilding people to help get lean for bodybuilding shows. And that’s something that puts you at risk.

Dr. Elkin:              And one other thing, Ben, that’s very important, ibuprofen or NSAIDs, nonsteroidal anti-inflammatory agents, commonly used by bodybuilders and not just bodybuilders, people in general. I’m very bullish on trying to avoid this stuff and myself and my patients. Acutely, it’s fine to take, but on a regular basis, and there’ve been many bodybuilders who have developed renal failure as well, taking. And there’s actually a case report that I read in 2023, yeah, last year of a young bodybuilder who was taking ibuprofen ended up in the merchant room with rhabdomyolysis. So that’s another thing to be on the watch for.

Dr. Weitz:            Absolutely. I know my share of professional athletes who ended up needing kidney transplant due to taking nonsteroidal anti-inflammatories. Interestingly, there was a period of time that nonsteroidal anti-inflammatories like ibuprofen were actually recommended to reduce your post-workout soreness. They actually claimed that they would help you recover. So it was really common at one point for a lot of athletes to automatically take nonsteroidal anti-inflammatories after their workouts thinking that it was actually beneficial. And in fact, you’re putting yourself at risk. Another thing that bodybuilders and fitness people do sometimes to help lean out is to take thyroid. Now, if you’re hypothyroid, you have a medical condition, your thyroid’s not producing enough thyroid, there is certainly a good reason to take thyroid medication, and there’s a safe way to do it, knowing what your levels are, taking appropriate levels, monitoring it. However, a lot of bodybuilders and fitness people take thyroid even though they don’t need thyroid just because they’re trying to increase and put themselves in a hyper thyroid state so that they’ll burn more fat. In fact, they may end up burning more muscle and put themselves more at risk for rhabdo.

Dr. Elkin:              I think we covered it.

Dr. Weitz:            So I think the message to get from this for the average person is if you’re going to be exercising intensely, and we recommend that everybody do exercise intensely, that you slowly ramp up to it, slowly increase your intensity, your frequency, and your duration of exercise, make sure you’re fully recovering. So get your exercise in, but do it safely. So now that we’re wrapping up, Howard, why don’t you tell our viewers how they can get in touch with you?

Dr. Elkin:              Okay, great. You can get in touch with me by two websites. One is heartwise.com, and the other one is beyourownmedicaladvocate.com, which is actually for my book that I put out a year ago. And on Instagram, it’s D-O-C-H Elkin, Doc H Elkin, and on Facebook, it’s HeartWise Fitness and Longevity Institute. So please feel free to contact me and follow me on social media.

Dr. Weitz:            That’s great. And I’m Dr. Ben Weitz. You can contact me through my website, D-R-W-E-I-T z.com. If you want to do a functional medicine consultation, you can call my office at 301-395-3111, you can also follow me on social media on Instagram @drbenweitz, and follow this podcast, the Rational Wellness Podcast. You can watch it on YouTube, you can listen to it on Spotify and Apple Podcasts. And if you enjoy it, please give us a five star rating and review, and we will see you next time.

 

Charlotte Blease, PhD, and Cosima Locher, PhD, discuss The Nocebo Effect 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

1:45  The placebo effect is when a patient feels better after taking a sugar pill of some other treatment that is not thought to be able to help them, because they believe that it will help them.  When a scientific study is conducted they often have a placebo arm with one group getting the pill with the active ingredient and the other group getting a pill without the active ingredient, which is referred to as the placebo group.  And yet a significant percentage of the patients who get the placebo improve.  The nocebo is sort of the opposite of the placebo in that if the patient believes or has fears or expectations that they are likely to have side effects or a negative result from a medication or treatment, they may have such negative effects.  The book The Nocebo Effect: When Words Make You Sick is designed to bring awareness to the nocebo concept, which has been much less researched than the placebo effect. And this book also attempts to bring some solutions so that nocebo effects occur less frequently.

 

               



Charlotte Blease, PhD is a philosopher and health researcher at Beth Israel Deaconess Medical Center, Harvard Medical School, and the Department of Women’s and Children’s Health at Uppsala University, Sweden.  The book that Charlotte and Cosima helped write is The Nocebo Effect: When Words Make You Sick.

Cosima Locher PhD is a psychologist who has published in leading medical journals and is the co-founder of the Pain Net, an international network of researchers interested in chronic pain with a special focus on the placebo and nocebo effects.

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

 



 

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 on The Nocebo Effect: When Words Make You Sick, which is a new book with two of the authors. So, Charlotte, maybe you want to introduce yourself.

Charlotte:            Okay. So my name’s Charlotte Blease. I’m a researcher at Uppsala University in Sweden. I’m affiliated to digital psychiatry at Harvard Medical School, Beth Israel Deaconness Medical Center there. My background’s very interdisciplinary as a health researcher. One of the topics I’ve been interested in is the placebo effect and the nocebo effect, which we’ll get into.

Dr. Weitz:            Great. And, Cosima, can you introduce yourself?

Cosima:                Yes, thank you, Ben. So my name is Cosima Locher.

Dr. Weitz:            Cosima.

Cosima:                Yes, exactly. I’m based at the University of Zurich, which is in Switzerland. My background is I’m a psychologist and I’m primarily interested in the placebo research, but also ethical considerations, health in general, and chronic pain primarily. Yes, exactly.

Dr. Weitz:            Great. So, the placebo effect is basically, my understanding is, when someone such as a patient feels better after taking a sugar pill or some other treatment that is generally not thought to be able to help them with whatever condition or symptom they’re dealing with, such as pain. It’s generally thought that they feel better or their condition improves because they feel that they have been given a pill or a treatment that will help them. If they’ve been told that it will work and they have confidence in that, it increases the likelihood that they’ll feel better.  Now, we often conduct scientific studies to prove the efficacy of drugs and medical treatments by comparing a group of patients that take the pill with the active medication and another group that takes a identical pill that doesn’t contain the medication, what we often refer to as say, a sugar pill.

                                Now, the placebo group is generally not expected to improve while the group that gets the medication is. Except that we’ve discovered over time that a significant percentage of patients who get the placebo group, who get the placebo treatment or pill, actually do improve. And so this has been referred to as the placebo effect, and there’s been a ton of research going on about this.  And the nocebo is sort of the opposite of the placebo in that if the patient believes or has fears or expectations that they are likely to have side effects or a negative result from a medication or treatment, they may have such negative effects.

                                The book The Nocebo Effect: When Words Make You Sick is designed to bring awareness to the nocebo concept, which has been much less researched than the placebo effect. And this book also attempts to bring some solutions so that nocebo effects occur less frequently. Perhaps you can both weigh in a little more on what exactly is the nocebo effect and why it’s an important concept?

Charlotte:            Sure. I can kick us off. The nocebo effect, to characterize it, is often depicted as this malevolent or evil twin of the placebo effect. So it is this effect that arises when patients or people in general anticipate some adverse health outcome. And they may have learned this health outcome somehow through medical encounters. This is something we discuss, our contributors in the book discuss in various ways. So that words matter in medicine, what you doctor says to you matters, or your psychotherapist. Something that Cosima has written about. But also what you believe is going to happen or what the outcome is going to be can affect your health and potentially in a negative way.

Dr. Weitz:            Right.

Cosima:                Yeah. Of course, this is all very important also for clinical practice. So this is also something that I’m quite interested into look what happens then in the clinic. And if you think how doctors for example, introduce when they give a medicine, what this can also have in terms of side effects, that this is very crucial the way how this information is being given. So we also talk about this in our book. Primarily I think [inaudible 00:05:30] talk about what can clinicians do to minimize this information about side effects. So this is very hands-on also in clinical practice and very relevant. And it can really make a change, so words are very powerful also in the opposite way, as you said, the counterpart of placebo.

Dr. Weitz:            Yeah, I do think that’s some really important points. I do think that it’s underappreciated from both patients and even practitioners how important the placebo and the nocebo effect are. I think a lot of physicians don’t necessarily think about it as much as they should in their communication with their patients.  One of the things that I was surprised to read about in your book, was actually when you remarked that, “53% to 89% of physicians in the U.S. actually knowingly prescribe placebos to their patients.” Meaning, they’re giving them a treatment that they don’t think it really has the ability to help them, but they do it just because they want to help their patients and they tell the patient that it’s going to help them.

Charlotte:            Yeah, it’s a fascinating finding. What’s interesting is that you see in lots of countries worldwide, these kinds of surveys have been conducted among clinicians internationally. You do find, depending on the sample size, but quite high percentages of doctors say that they do this.  We’ve done some survey work, I did some survey work in the States, in Boston, on this. There are a variety of reasons why doctors do this. Some of them, they do want to offer something. Some of it is a bit of a performance anxiety thing that they want to be able to offer the patient something. Sometimes they don’t know what to offer. And they’re not sure what’s going to work. And they might present, and this is what Cosima is saying, “Words matter.” The performance, the presentation of what it is you want to offer the patient might influence them to think that this… Might, if you will, engender some hope.

Dr. Weitz:            Do you have maybe one or two examples of why a physician might offer a patient in this situation?

Charlotte:            Yeah, it may be that they’re not… Fatigue is one of the many… Who isn’t feeling tired? But a lot of time when people go to the doctor, they might say, “Look, I’m not getting any sleep. I’m excessively tired.” And that could be a really serious underlying health problem. But, if a patient presents with that in combination with other symptoms perhaps the doctor might offer them or suggest a vitamin or something like that. They might suggest some dietary supplement.

Dr. Weitz:            After all, since we know vitamins can have no benefit. Just kidding.

Charlotte:            Well, you know, if this issue…

Dr. Weitz:            Coming from somebody from the functional medicine world.

Charlotte:            Right. It’s this sort of gray area where you’re suggesting something. And in this case, the vitamin or the supplement or whatever, could do something to the patient. But is it also in addition potentially going to elicit a placebo effect? Are they going to feel a little bit better? And it’s these kinds of nudges where we get into the gray area between transparency being completely honest and the doctor saying, “I don’t really have anything to offer.” Versus, I’m willing to offer something to give some kind of hope or potential benefit.

Dr. Weitz:            I would like to also posit that I suspect that one of the reasons why in the United States physicians may feel compelled to offer some medication even if they know that they likely have no medications that really address the problem, is because our healthcare system, which is essentially run by insurance companies, requires doctors to have very short office visits. You need to get in an out of that room, and the patients want to feel like they’ve been given something. So, I think there’s a tendency to prescribe something.

                                A situation that I’ve seen over the years very commonly is a patient comes in with a cold or a flu. Which we know is caused by a virus. We have no medications that really control viruses, for the most part. So, they’re given a prescription for an antibiotic and the patient feels like that’s going to help them. I think the physicians feel like, “Okay, now I’m done with the visit. I did something to satisfy the patient.” And unfortunately, it sometimes has untowards side effects. Like in this country, we have this overuse of antibiotics that have led to bacteria that are not responding to antibiotics anymore.

Charlotte:            Right. I think that’s a universal concern in western countries, this overprescribing of antibiotics. As you said, the classic example, antibiotics for a viral condition, it’s offering the patient something.

Dr. Weitz:            Right. Yeah.

Cosima:                I think this is a very important of course, explanation of looking at the doctor’s side and what is happening. And you have this very limited hour and time. This is also something that is I think also very common in several countries. But it’s also when you look at the patient for example, I did a lot of research in the field of chronic primary pain. So where it’s not about the etiology. So in chronic secondary pain, we know what happens for example, a broken leg or whatever, full of pain because of cancer or because of an accident.  But in chronic primary pain, according to the new IDC-11, it’s quite unknown what is the etiology. And these patients, they do really suffer and they have real pain. And they do often doctor shopping. They want to have something that helps them. And I think Charlotte, what you mentioned with hope is so important, right? They really have this desire for relief and they are desperate. And this is very, very understandable. I think what happens there is also this feeling of I have to give this patient something because this patient is now in a really bad state.  There are studies which really show that when a physician can do something in comparison when the physician is feeling himself or herself helpless, this gives in the brain a kind of benefit. So I think this is obviously also what physicians have and want to do, helping the patient. So this is all quite complex, I would say.

Charlotte:            Definitely.

Dr. Weitz:            Let’s switch to nocebo, and let’s talk about some common situations in medicine where the most nocebo effect comes into effect. You mentioned the use of statin drugs as a common situation, because so many patients have heard that statin drugs are going to cause muscle pain, or brain fog or other symptoms.

Charlotte:            Yeah, I mean, I think it’s as many as about 200 million people take statins worldwide. But there’s been some fascinating studies show that when patients are given placebos in clinical trials of statins that up to 90% of the side effects could be attributable to nocebo responses. So, it’s this interesting confluence of public awareness through media. So media can play a role here, what you’ve read. Some of it could be to a certain social contagion, so people anticipate what they’ve heard on the grapevine, so to speak, all the people, all their patients.

                                But some of it may also be… And this is where we get into in the book, what do we mean by nocebo effect? Is it the genuine anticipation, this is going to be harmful that induces it? Or, are people saying that they’ve got some of these conditions? And they may have some underlying somatic complaint that they’re attributing to the statin. So it’s disentangling these is another aspect of really getting into the science and it’s complicated. You’re going to hear us say, “Everything is complicated.” It’s just a really complicated area.

                                And it’s important not to be too reductive. And this is why this book is so important because there really hasn’t been anything published on this evil twin, this nocebo effect. And how best we study it, and what exactly it is, really honing in on it.

Dr. Weitz:            And it’s certainly, it’s not as simple as it’s just completely a psychosomatic thing. Because there are patients who like you just mentioned, maybe they do have some underlying muscle pain and had that before, and now they’re attributing that to maybe taking the statin drug. There’s some patients who are having a psychosomatic effect and they think they’re getting muscle pain, and they’re not. But there are some patients who are actually getting muscle pain, some patients who actually their health gets worse. And there’s even been patients who’ve been reported to have died from the nocebo effect. Isn’t that correct?

Charlotte:            I’ll let Cosima answer this controversial…

Cosima:                This is also complicated. But there is this one famous study where a patient apparently felt like almost dying because he wanted to suicide himself. And he took a lot of these drugs, and he was currently, I think in a study, a patient of a study. And he wanted to suicide himself and took an overdose. And then in the hospital it turned out that actually this person was in the placebo arm of the study.  So, I think that many studies also you know, studies…

Dr. Weitz:            And that person died?

Cosima:                No, that… But almost. It looked as if, all the symptoms where you would say someone almost died. But I think there are always case reports when you do… Whatever field you’re in, you have case reports, and of course, this is one line of how you can examine a phenomenon. But I think that it’s also very important of course, to do replications. Not even of a case, but also of a study. Usually when a phenomenon is new, and people are very excited about it, we see that the effects are quite large. And we have maybe a power issue, because we have small sample sizes. Then it’s always very important of course, to replicate the findings, to network, or meta analysis, and reviews. I think the more we do that, the more accurate we can achieve.

Dr. Weitz:            But of course you can’t have a placebo controlled study about nocebos, right? Or can you?

Cosima:                Yeah, there’re very interesting ways of how to examine nocebo effects, of course, yeah. I think one person once said there is… I mean, most research has been done in the field of placebo because this is the usual control group. When you do for example, I did a lot of studies in antidepressants. When you do a placebo study in the antidepressant study trial, then you also have the nocebo effect there because you can look whether the two arms, antidepressant and placebo differ in terms of the appearance of side effects. So then you have the nocebo in there as well.

                                I think Charlotte mentioned that we have, with statins so many side effects. The thing is, it really matters how you frame side effects, whether you say, “Two out of 10 people have whatever, nausea.” Or whether you say, “Eight out of 10 do not have nausea.” So, there is a systematic review which really show that this makes quite a big difference, whether you positively frame it or negatively frame it.

Dr. Weitz:            Well actually, let me… What I mentioned as a possibility, as a question. Do we have cases of patients who have parameters about their health whether they be measurable biomarkers, or other parts of their condition that get worse, as a result of nocebo?

Charlotte:            I can give you one example of a… And this is again, just a caveat this of what Cosima is saying. Part of this book is an invitation to other researchers. We need replications of these studies. We need larger sample sizes.  What a really interesting study with people with dust mite allergy, and giving them a milkshake with the allergen in it. In a sense teaching them, but like Pavlov’s dog. You’ve heard of Pavlov’s dog with the bell ringing and then the dog salivates. Every time the bell rings, dinner is there. You just need to ring the bell and the dog’s salivating, ready to eat. But this was in a sense, looking at this possibility of conditioning with nocebo effects with patients. What they find was, presenting them after this learned conditioned response, that you could offer the milkshake and you would get the inflammatory biomarkers were there among patients, as if they had been given a touch of the allergen.

                                Again, we need more of these kinds of studies. But there is some interesting work. Other studies are on what’s often been called anticipatory nausea. So you can induce motion sickness, for example. Give people fruit juice or something, induce motion sickness. The same setup. And then just offering them the juice will make them think they’re ill.  And this is really important, of course. So many drugs, cancer, many medications have linked to this kind of side effect, that puts people off taking the medications. So, anything we can do to minimize these kinds of effects where possible is going to be critical.

Cosima:                Yeah, and I think it’s also very important that the nocebo, so all the examines, also in the book, we don’t only focus on research where we have this nocebo/placebo. Because nocebo is always there also in the varum, in any kind of drugs.  There is a very nice study where patients wants openly reduced their drug. I’m not sure whether it was opioids or whatever, so they reduced whatever they take. And they somehow expect side effects, right? Because this is what you would expect with reducing opioids. Once this was openly done, so the physician, they know when they reduce their intake or infusion. And once it’s unclear, so they say, “Look, there’s this machine, you have the infusion.” Over a longer period of time, at a specific point this will be reduced but we don’t tell you when exactly.

                                We say that the side effect’s due to drug reduction. They are really different between this open and hidden reduction. This shows that the nocebo effect is also present even if we don’t have a placebo pill that is examined. So, I want to really underline what Charlotte said, how crucial this is in clinical practice. It’s not only if you prescribe a placebo, it’s with every varum.

Dr. Weitz:            Now, you mentioned cancer. And you talk in the book about how the nocebo effect can come up in the context of cancer care. This is a very complicated situation for doctors, especially if they’re providing a patient with a diagnosis, or making treatment recommendations about a life-threatening condition, like a stage IV cancer diagnosis. I personally have noticed a number of patients who were suffering with a metastatic cancer, stage IV. They really didn’t have a very good prognosis. They were provided with some form of treatment, typically chemotherapy, or some other drug that’s supposed to help with the cancer.  It’s my understanding from the situation that I’ve seen that the treatment was palliative but the patient’s thought it was curative. I don’t actually know exactly what the doctor said to the patient, but the patient would come in saying, “Oh yeah, I’m getting better. This is going to cure it.” Either the doctor wasn’t clear about how they explained it. I’ve heard of situations where doctors will not tell the patient exactly how grim the diagnosis is, and maybe tell the family.

                                It’s a difficult situation for the doctor because the doctor is required to make sure the patient understands the condition, gives informed consent for treatment. On the other hand, if there is a glimmer of hope that the patient might get better, you’ve got to be really careful as a physician, or you should be careful not to just say, “Hey, you’re almost certainly going to die. This treatment at best is going to give you a couple of months.” Why would the patient even bother to do it?

Charlotte:            It’s a really tricky area. And as you say, the doctor is walking a tightrope between balancing these different ethical concerns. On the one hand, they are really required, and this is, for most of the history of medicine, doctors had a therapeutic privilege. They didn’t tell the truth to patients. They used their own discretion about what they thought was the right thing to do.  From the mid-20th century, after the second world war, some of the atrocities with Josef Mengele, the Tuskegee syphilis trial in the States, we’ve reached an awareness that part of medical ethics codes, patients should be respected. And they should be respected to make their own decisions about their treatment plans. We respect the patient’s autonomy to make their decisions. To do that, you’ve got to furnish them with the truth.  This is where the nocebo effect gets really tricky because you want to balance honesty and openness with not causing harm to the patient. In these cases…

Dr. Weitz:            Maybe giving them some sense of hope.

Charlotte:            Or giving them hope, and benefiting the patient. So, the doctor wants to benefit the patient, maximize the treatment. It comes optimizing as far as possible. First, do no harm, of course. So minimize sources of harm, including nocebo effect, which can have consequences. Unless we say that if you anticipate side effects, one of the biggest reasons that patients will quit is because they don’t like side effects for the treatment plan. So, balancing that with the patient’s decision about what it is they want to do and to think about what it is they want to do, weighing that out for themselves about what the best decision is, against their values and so on.

                                This is not an easy area. We do discuss this in the book. We have an eminent medical ethicist who’s contributed, Mark Wenonley, from Italy. Who has contributed a chapter on medical ethics, and what it is you should do in these scenarios. There are no clean answers to this. This is what makes medical ethics an interesting area of research. So it’s tricky.

Dr. Weitz:            You give some recommendations for maybe ways that doctors can communicate the situation in say, a cancer diagnosis that’s not that good. But do it in a way that doesn’t just totally… It minimizes the likelihood of patient having a nocebo effect, essentially.

Charlotte:            Yes. On some of that comes down to what Cosima said, it’s the framing of the information. It’s how you convey it. It’s also the framing, so it’s the words that you use that convey the same facts, but doing it in a way that might lead to a more beneficial response from the patient side.  Some other suggestions that have been made are this idea of discussing with the patient that they might not want to know the side effects. So, medical ethicists talk about authorized concealment. So you might have a discussion to say, “Look, there are some serious side effects here. Do you want to know them?” This I think, is perhaps more of the kind of philosophers or medical ethicists theoretical dream. In reality, I don’t think these things necessarily work because we’ve all got the internet. Apparently, health searches are second only to porn searches.  So it’s one thing sitting with your doctor and saying, “Yeah, I don’t want to know.” And then you leave the doctor’s office and you say, “To hell with it, I want to find out what’s…” You Google it, somebody tells you.

Cosima:                The patients want to know, so what we surveyed, right?

Charlotte:            They want to know, yeah.

Cosima:                They want to know, so I think very important to mention that patients want to know, so basically the maturity. I think it also comes down, besides all the strategies, authorized concealment, but also the way we frame and education. I think it always comes also down to the patient-physician relationship. So it really matters whether you trust your physician, whether you feel guided by your physician. I think that will probably be the best way of concentrating on the positive or informative information.

                                Also, I think it’s important to know that of course, positive expectations are good, so this is what we mean with we try to boost interventions by… But, actually, realistic expectations are the best. This is also a study shows. Negative expectations of course, is not what we want. And this is also with minimizing harm. We don’t want to be over positive. This is actually also harming patients. I think it’s about setting realistic but also empathic around expectations, being in a trust-based relationship. It all comes down sometimes to the relationship between patient and physician.

Dr. Weitz:            Yeah, I do think that that’s something that physicians probably don’t get that much training in, is how to effectively communicate with patients.

Charlotte:            What Cosima said in terms of the relationship is so central. Patients that say they want to get the information from their doctor, they get it online because as you said Ben, they have very limited amount of time with the doctor. Doctors are under serious pressure too. Time is the most vital resource in healthcare.

                                So, they will look online if they don’t get that information. But they want to get it from the doctor. It’s about signaling, as Cosima’s underlined, if you overcompensate or you try too hard to instill hope and then you go overboard, and the patient then doesn’t quite trust. I have a very good friend, she’s got a rare condition and she says, “God, when they offer me another… I know when they’re offering me placebos. And I just can’t stand it because I don’t trust them anymore after that.” On the other hand, she recognizes why some doctors may do this occasionally with her symptom, obviously, in a chronic condition.

                                So it’s this again, balancing act between signally competence and empathy. You understand that those are two facets also of the demeanor of the clinician, that can be important in optimizing a placebo effect response to… Potentially minimizing nocebo effect. But for that, you’ve got to be in the realm of honesty.

Dr. Weitz:            The last chapter in your book you mentioned, or the next to the last chapter of the book, you mentioned some of the social phenomenon involving the nocebo effect. I thought this was a great title of a chapter, it’s called, From Genetical Shrinking Panics to Humming Giraffes: The Many Faces of the Nocebo Effect.  I guess there have been some social phenomenon in which the nocebo effect has taken place.    And one of the things you mentioned is this Havana Syndrome situation which took place in Cuba. I didn’t really understand it that well, but apparently a bunch of Americans working in Cuba, working for the state department, et cetera, had a series of symptoms and there was this investigation into whether some new weapon was being used by Russia. It sounds like from the latest information that there was really no evidence of some new weapon that cause these symptoms.

Charlotte:            Yeah. Go ahead, Cosima.

Cosima:                I think yeah, it’s very important, I think these chapters. We also have this media chapter where we see how influential the media and social media of course are. Also, with the idea of, I think it goes viral, and people, they read of course, the incident and so on. This is really crucial in our daily lives. I think we have to really consider new ways of communication. I think this shows really nicely, all these chapters show that this is not somehow a disentangled context between the physician and the patient, but rather more we have to always consider the context.

                                This is also something that we know from placebo research. So it’s a much more complex again, than only this interaction between two people. I think again, we see with this example that you, I think, summarized really nicely, is that of course, it’s not going down to the sugar pill again. So it’s much bigger actually what we can subsume on the nocebo.

Charlotte:            What I would add to that is, it gets into disambiguating what the nocebo effect is here. So, we do have these other… I mean, what happened with this Havana Syndrome, or a more recently which our colleagues, Mike Bernstein and Walter Brown have written about is the bed bugs situation. You might have read about it in the… You start itching and so on. Oh, I’m going to read about it in the nocebo effect. In France and Paris, and then it was people were staying in hotels and then traveling the rails.

Dr. Weitz:            I heard a little bit about it. Maybe you can tell us more. I don’t really understand it.

Charlotte:            Yes. It was this outbreak of bed bugs in France and Paris apparently in hotels. I’ve been in France, that’s why [inaudible 00:35:41]. You start to get this feeling. And I had a friend who was in France. It became this slightly anxious thing as if it was in continental Europe. People traveling on the trains, and where this thing was spreading, the bed bugs were spreading everywhere. So it’s this issue of, were bed bugs actually making people itch in bed or was it really the source of… You can get sores and so on.

                                I have a friend I see who came back from Venice. And she said, “I’m convinced we’ve come back with bed bugs.” They did a search and they couldn’t find any bed bugs. So it’s this issue of the nocebo effect. Is it a case of, it could be social contagion sometimes where we’re reporting things. It’s a social effect, sort of conformity to believe. We’re picking up beliefs and we’re communicating them to others. Or it could be nocebo effect too causing these issues. Or it could be some sort of misattribution. There’s a variety of things going on here, which makes it a fascinating topic, but a really tricky one to disentangle.

Dr. Weitz:            Yeah, especially…

Cosima:                And I think Steinkopf also… Sorry.

Dr. Weitz:            Go ahead.

Cosima:                Maybe just to add, Steinkopf also very nicely shows that the placebo effect itself is something very human and evolutionary, adaptive, right? So we show signals for example, when we have placebo effects. When I’m in pain, because of a nocebo, I show signals. And this is like a signal theory of other people responding to me. This is actually an adaptive thing that is happening. But it can be, as shown by this example, why really was going on then, when it goes viral. That was just an add-on.

Dr. Weitz:            Yeah, and adding in the information being spread over Facebook and these other social media sites, often some misinformation or information about some condition… I’m sure the bed bug thing probably had a lot to do with being how we communicated with each other. It’s easy for something like that to get spread to a lot of people very quickly.

Charlotte:            Absolutely. It becomes this almost belief, conformity too. So, extracting that from a genuine cycle, biological effect, it requires a lot of ingenuity.

Dr. Weitz:            Yeah, I think there’s some of this going on right now over to what extent is 5G and EMFs, what negative effects they’re potentially having on health, compared to what negative effects people perceive are happening that maybe aren’t.

Charlotte:            Yeah, absolutely. There’s this bit of graffiti around where I live in my neighborhood, lots of 5G posters and everything. It creates a certain anxiety as well. And nocebo effect is one of these things that can be, anxiety can be elevated with. It’s an anticipatory response. As Cosima was saying, there’s good evolutionary reasons why we have these anticipatory responses.  So yeah, it’s a preparedness for something. Signaling in whatever way that something negative is about to happen, we’re attuned to that. So, managing this in a social and a cultural level through mass media, social media, not to say anything about the doctor’s office, if you will. It’s a broader concern, what do we do from a public health perspective? How do we control messaging? It’s nocebo mind control messaging [inaudible 00:40:04]. We’re getting into politics here.

Dr. Weitz:            Yeah, yeah, exactly. I tend to be a big free speech person. I think it’s a bad idea to just ban messages, take down YouTube videos that you disagree with. I think it’s much more effective to just do a better job of spreading the correct information. I think good ideas will overcome bad ideas. If you simply take down the information and hide it from people, then people will feel like there’s information that’s being hid from them. Some people will be more attracted to it, so I don’t think there’s really a realistic way of stopping people from putting out some bad information.  I think the more we can get people educated.

Charlotte:            Agreed.

Dr. Weitz:            And how to analyze information, especially about medicine or science. And how to figure out what is a good source, a good way to understand information. That will be a better protection against bad information, I think.

Charlotte:            Yeah, and education, right?

Dr. Weitz:            Right.

Cosima:                Education is really the word that you could also find in our book over and over again. I think also patient involvement; I think this is also why we are very much striving for patient involvement. Also in research, right? So, the more educated we are, the more we educate patients and the more we learn from them as well. It’s very important to not have this hierarchy but to rather more be of the same eye level. Then I think you can start to learn from each other.

                                I think for the example of 5G, what we know from placebo is that this is something that we can also bring down to the so-called Bayesian approach. The brain is always one step ahead. So we always anticipate. When you take a glass, you anticipate how it’s been put on your mouth. This is what you usually do. This is very automatic. When you learn, it’s only when you do an error. So only when something, when my coffee spreads out, this is when I learn, “Oh, I have done something wrong with me movement.” When you come to 5G, you would actually have to have a negative example of why this is not the case. This is so hard in these complex fields to learn from exams that really are a proof for you, that 5G is not harmful. And this is only so possible.

                                I think this is why it’s a very, very complex field. And why I really want to underline the importance of education.

Dr. Weitz:            Okay, so to wrap up, especially since my podcast is devoted to health, what are some of the main messages that can be learned from both patient and doctors and practitioners on how to avoid the nocebo effect?

Charlotte:            From a medical perspective… I’m going to leave that, maybe the medical side to Cosima to answer, what can clinicians do? I would say from a patient perspective, one of the things that I’ve been interested in, in my research in digital health is online record access. As we know in the U.S., the 21st Century Cures Act, patients can get online and read their medical records. They can see test results, and they can see a little bit of the… They can see the narrative.

Dr. Weitz:            A little bit, to some extent, yeah.

Charlotte:            Well, doctors shouldn’t be hiding this stuff, that’s the point.

Dr. Weitz:            But we’ve also created this big mess, when we set out to set up medical records, we decided, oh the free market is going to fix this. So, there’s a thousand different companies offering a thousand different online systems that are not compatible. We should have I think, made sure that everything was built on a compatible platform so that if you go to see a doctor at one hospital, and you see a doctor at another hospital, those records are not shared, they’re not compatible. What gets on there is somewhat limited. Part of it is time. Part of it is other things. So, we might get an x-ray, they don’t put the x-ray on your medical records. You might have the doctor’s note about the x-ray, that’s about it.

Charlotte:            Right. This is a whole other podcast that we could do.

Dr. Weitz:            I know. I know. I know. But it’s too bad that the medical sharing is…

Charlotte:            The lack of interoperability between all of these systems. It’s chaotic. But what’s really interesting there is, when you offer patients access, one of the things that they report benefits in, are understanding the medical information better, including side effects of medications. So, this is a perfect vehicle. It’s a perfect storm for increasing nocebo effect.

                                I guess from a patient perspective, I would say if you don’t… I mean, it’s really about the individual’s preferences. If you don’t really want to know… This is something that I have actually have incorporated into… If I don’t want to know this, I can not want to read the side effects sometimes, minor medications. I mean, if it’s a bigger procedure, you want to know. But for certain medications, I just don’t read, I don’t engage because I don’t want to tempt my own underlying cognition to lead my astray into a whole set of problems that I don’t need in my life. So I always park it there. That’s my own lived experience, if you will.  There’s so much transparency now in healthcare that nocebo effects could be elevated.

Dr. Weitz:            Yeah, you have that chapter on cancer where you mention that patients can go into their doctor and tell the doctor how much they want to know ahead of time, before the doctor just tells them.

Charlotte:            Yeah, that’s another strategy. You’re strengthening the relationship with your doctor too because you’re letting them know what it is you want to know. And that can change, and it can change in a relationship with an oncologist as well, where you decide perhaps at the beginning you don’t want that. Your decisions may change over time about how much information you want, and when you want it.

Dr. Weitz:            What do we know about the medical legal aspect of that, like if a patient says, “I don’t want to know all the consequences of this medication.” Or, “I don’t really want to know what my likelihood of dying is.” And then some legal situation holds up after that, is the doctor protected?

Charlotte:            I’m not a medical lawyer. I would want to weigh in on this. So I’m going to stay clear of this.

Dr. Weitz:            Right, I know that. But that’s an issue that I could see making this situation complicated.

Cosima:                But maybe I think it’s so important when it comes down to, besides the legal issue of course, empowerment, right? I think this is what shows really, outlines how important it is to, when you give the patient an empowerment, I think then this eye-level relationship happens. When it comes to the clinician side of things, this eye-level relationship is of course something where I would say, this is what we can summarize from today, that we have a relationship that is trust based. And again, with this empowerment, we also heard that the information the way the framing is given is so important, to frame it positively or negatively.  This is actually also something where I would say this is hands-on very easy, the way you frame something, right? I think that the third thing is about expectations, what we have heard. So, how can I look, the way I frame it, creates positive expectations? I think information, education, patient/physician relationship are three core elements of clinical practice change in the way that nocebo effect can be minimized.

Dr. Weitz:            Right. Okay. Thank you very much for this important discussion. We’ve brought up as many questions as answers. But that’s important to start thinking about this. I think both patients and physicians can reduce the risk of nocebo effects by patients can tell their doctor what they want to know. And limits to which they want to hear negative information, and doctors have to find ways to correctly inform the patient but frame it in a way that there’s some emphasis on the positive aspects of it.  I think you mentioned in the book somewhere about a doctor explaining to a patient who most likely is going to die from a treatment, but frames it in a way that I think 25% of the patients improve. And we’re going to do everything to make sure that you’re in that 25%.

Charlotte:            Yeah. And that’s critical to subsequent health behaviors too.

Dr. Weitz:            Right. Yeah, good. Okay. Great. Everybody needs to go buy the Nocebo Effect book. Is it on sale now?

Charlotte:            To pre-order, yes.

Dr. Weitz:            Okay, pre-order.

Cosima:                I think it will be 19th of March.

Charlotte:            19th of March, yeah.

Dr. Weitz:            Okay. And it’s going to be available everywhere?

Charlotte:            I know it’s available on Amazon. Beyond that, I’m not… It’s Mayo Clinic Press, which should be available on Mayo Clinic’s website too.

Dr. Weitz:            So the book is the Nocebo Effect: When Words Make you Sick. Okay, thank you.

Charlotte:            Thank you.

Cosima:                Thank you very much. Thank you.


Dr. Weitz:            Thank you for making it all the way through this episode of the Rational Wellness podcast. For those of you who enjoy listening to the Rational Wellness podcast, I would certainly appreciate it if you could go to Apple Podcast or Spotify and give us a five-star ratings and review. That way more people will discover the Rational Wellness podcast.

                                And I wanted to let everybody know that I do have some openings for new patients, so I could see you for a functional medicine consultation for a specific health issues like gut problems, autoimmune diseases, cardiometabolic conditions, or for an executive health screen, and to help you promote longevity and take a deeper dive into some of those factors that can lead to chronic diseases along the way. That usually means we’re going to do some more detailed lab work, stool testing, sometimes urine testing. We’re going to look at a lot more details to get a better picture of your overall health from a preventative functional medicine perspective. So, if you’re interested, please call my Santa Monica, Weitz Sports Chiropractic and Nutrition office at 310-395-3111, and we can set you up for a new consultation for functional medicine.

                                I’ll talk to everybody next week.

 

Valentin Prisecaru and Jeff Ingersoll discuss Genomic Testing 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

5:02  Genetics or the Human Genome refers to the genetic code that is made up of only four letters, A, G, C, and T and this code about 3 billion letters long.  The majority of the genome is still kind of a mystery because we don’t know exactly what it does.  But we do know about 20 or 30,000 genes that code for proteins or for RNA or a few other things.         

 

  



Valentin Prisecaru is a scientist who with Dr. Peter D’Adamo helped develop the Opus-23 platform that is the basis for the Genomic Insights, the Genomic Health Profile offered by Diagnostic Solutions Lab.  Diagnostic Solutions Lab web site is DiagnosticSolutionsLab.com  and the phone is 877-485-5336.

Jeff Ingersoll is the President of Diagnostic Solutions Lab, which besides the Genomic Insights profile, offers my favorite stool test, the GI Map, a cytokine panel Cyto DX, an organic acids profile, an amino acids profile, as well as food allergy and foods sensitivity panels.

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

 



 

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, I’ll be having an interview with Jeff, who’s president of Diagnostics Solutions Lab and with Valentin Prisecaru about Genomic Insights, the Genomic Health Profile, which uses the Opus23 Informatics platform. And this allows clinicians to customize reports using an interactive dashboard that curates a patient’s genomic data in real time by using the latest medical literature databases and metadata sets, whatever those are.

                                                Jeff Ingersoll is the president of Diagnostic Solutions Lab, which besides The Genomics Insights Profile, offers my favorite stool test, the GI map. They also offer a cytokine panel, CytoDX. They offer an organic acids profile, an amino acids profile, as well as food allergy and food sensitivity testing. Valentin Prisecaru is a scientist who, with Dr. Peter D’Adamo helped to develop this Opus23 platform. That’s the basis for this Genomic Insights profile. First of all, I thought Jeff and Valentin, is there anything else you’d like to tell the audience about yourselves before we start discussing this genomics testing?

Valentin:             Well, Jeff can go ahead.

Jeff:                     Yeah, thank you. Thank you, Ben. I would say in full disclosure, I’m not the SNP expert, so Val will kind of carry this conversation. Yes, as a president of Diagnostic Solutions Laboratory, we have had the Genomic Insight testing available, and the Genomic Insight software was designed by Dr. Peter D’Adamo, specifically for our lab, to give the full realm of SNP information. It will give you 3,500 plus SNPs are evaluated and they’re in the software, but how you sort that can be up to you, but we also provide a dozen pre-curated methylation SNPs, cardio SNPs, just different versions that they can use in a pre-curated version. And Diagnostic Solutions also offers it as a data only file, if you would like to have all of the SNPs and use the Opus Pro software, which is Dr. D’Adamo’s kind of premier software.  So there’s different ways that we can help with the SNP evaluation. And then, when it comes to interpretation, I leave it to the scientists.

Dr. Weitz:           And Val, what more should everybody know about yourself?

Valentin:             Well, hey, that was a really good introduction by Jeff. What more do people need to know about myself? I started working with Peter, we were trying to get some projects off the ground back in 2013, 2014. Finally, in 2017, he was telling me, “Hey, he already wrote this program.” I wasn’t around too much back then. I guess he coded it in 2014 and ’15. I came out finally in 2018. He said, “You really got to check this thing out. It’s been operational for a couple of years, and you still haven’t come out to Connecticut.” So I went out there. He trained me on it, and it was just incredible. I was very happy to be a part of his team. A few months later, he hired me part-time just to help him with some things on it.  And I ended up being the number one editor for the program, just adding thousands of gene agent associations, SNPs genes, just a bunch of information. I’d scour the internet and load it up into the program. Then later on, I started teaching nutrigenomics for John Patrick University. Consulted with a couple other nutraceuticals and nut nutrigenomics companies, and now, I’m working with Designs for Health, which works with the Diagnostic Solutions Lab.

Dr. Weitz:           So you’ve mentioned several terms. I think it would be a good idea to spend a couple of minutes defining some of these terms. So we have genetics, we have genomics, we have nutrigenomics, we have genes, we have DNA, we have SNPs, which is short for single nucleotide polymorphisms. Maybe just give us a little bit of information about what exactly we’re talking about.

Valentin:             Absolutely. So the human genome is all the letters of the alphabet, and how many of them? So the alphabet has what, 26 letters. So in genetics, there’s only four letters, and really there’s only two letters because one always goes with the other. That’s just how genetics is. So you have A, G, C and T, and that’s your genetic code, and it’s about three billion letters long. The majority of the genome … it’s kind of a mystery. We don’t know exactly what it does, but we do know what certain genes do. So there’s like, just depending on who you ask, 20, 30,000 genes and these genes code for proteins usually, although sometimes they code for other things like pieces of RNA and some other stuff, which we can get into some other time.  You have several thousand genes, and these genes are a bunch of letters long. They can be as short as, I don’t know, probably 50 or a hundred letters or alleles, letters long, nucleotides long and they can be a thousands of nucleotides long. And this information is used to make the proteins. Some of these proteins look a little bit different. If there’s a variant or a difference in a SNP, a SNP is a single nucleotide polymorphism. Basically just means a single letter change, but it’s very fancy, SNP. So if there’s … usually people have a C and maybe 10% of the population in this one location on your genome, instead of C, these people have A. The letter A and then, that protein, that’s where that mutation is or that variant is, well, that protein just doesn’t work as well.

                                                So maybe that reduces the risk of cancer, but maybe it increases the risk of cardiovascular disease. So then you kind of want to know, “Oh, do I have the C or the A, because I want to know, should I eat an anti-cancer diet or should I eat an anti … heart healthy diet,” right? So that’s just a real, real simplification of the process, but it’s not too far from reality. So some people, they just have very high autoimmune disease risk. Others have more cancer risk. Maybe they have the BRCA gene. Others have a more cardiovascular disease. Some people, they’re just always getting sick. Always having colds, flus, et cetera, et cetera. So that can take a toll on the body. Based on these SNPs, of which there’s several thousand important one.

                                                I mean the most important one, there’s probably just a few hundred that are relevant in the common person. There’s some rare ones that one in 10,000 people have it or one in 50,000. Those are important too. As far as for the average person, there’s a few hundred that are important.

Dr. Weitz:           Okay, so my understanding is essentially when we run these gene panels, we’re focusing on these SNPs, these variants. And that gives us some sense of a person’s potential increase or decreased risk of certain diseases or understanding how they may process medications or how hormones may work in them or other things that can affect their health.

Valentin:             Right. That’s right. So those are all the different, basically subspecies or subcategories of genomics. So genetics is kind of just looking at one gene. Genomics is looking at multiple genes, like the whole genome. So what we do is nutrigenomics. So it’s basically genomics regarding nutrition, but then there’s also pharmacogenomics. So that’s genomics regarding some drug interaction or if you have that one SNP, yeah, you can’t take this one drug because it’ll mess you up for whatever reason, so that’s pharmacogenomics. So there’s some overlap between the two, of course.

Dr. Weitz:           Yeah, how accurate are these tests? I’ve heard that there’s some inaccuracies depending upon some tests over others. Are we talking about 99% accurate, or are there some tests that can come out with different results?

Valentin:             Sure. Yeah. Every test is different, and most of the SNPs that are reported by most companies, they’re fairly accurate, like over 99%.

Dr. Weitz:           Over 99%. Okay.

Valentin:             Yeah, but there are a couple of SNPs in particular that tend to be a little bit error-prone. That’s one thing I like about Diagnostic Solutions Lab is that they actually manually check these four SNPs. So there can be no uncertainty. Instead of 99% plus, it’s more like 99.9999% plus. And the SNPs are COMT, which is associated with anxiety, depression, cancer, all sorts of things, dopamine executive function. Then, there’s also the APOE, which is associated with the Alzheimer’s.

Dr. Weitz:           Right.

Valentin:             So everybody wants to know, “Hey, I want to make sure this is correct.” And I think Jeff can tell you a little bit more. Yeah, that’s one of the great things about the DSL.

Dr. Weitz:           Yeah, so the APOE … yeah, the most common is APOE 3 3, and if you have one or two copies of the APOE4 that puts you at increased risk for Alzheimer’s and possibly cardiovascular disease. Is that correct?

Valentin:             Yep, that’s correct and having the APOE4, having one copy of it, having two copies, it’s not that good. It increases your odds of dying of Alzheimer’s from 4% to 45%. So it’s really, really changes things. Having just one copy, it increases dying of Alzheimer’s, I think from about 4% to about 8%. So it’s not a huge risk, but there’s benefits to it. If you have the APOE4, you have some increased maybe cholesterol issues, some cardiovascular disease risk, and of course, increased Alzheimer’s. You have improved clearance of fat because you’re able to … that same problem where you’re depositing certain fats in your brain for Alzheimer’s later in life.

                                                Throughout your life, that improved clearance of fats reduces body fat. So people are less obese. Your APOE4, you have … it’s like a reduced risk of obesity and type two diabetes. And interestingly, type one diabetes and reduced lung issues like idiopathic pulmonary fibrosis, all these types of lung problems are reduced probably because your different organs don’t have as much fat deposited and probably runs better, your immune system probably runs better too, if you’re able to clear fat better, reduce risk of kidney problems, reduce chronic kidney disease, reduce fatty liver, reduce non-alcoholic fatty liver, pretty much every organ just runs better. If you got a copy of that E4. So I don’t even know what’s better,

Dr. Weitz:                   You’re saying this is one of the gene sets tend to prone to error in measurement.

Jeff:                     Possibly. So what you run into sometimes, when you’ve got multi allelic SNPs, it’s a little bit harder when you’re doing metagenomic reads. So you can do what’s called a direct measurement, which means instead of doing metagenomic reading, you’re actually targeting that gene and that position on that gene specifically and looking for … so you wouldn’t be able to run several thousand SNPs that way efficiently, but if you need to know for sure and kind of remove the uncertainty, you do it as a direct call measurement. And that’s what we do for those specific-

Dr. Weitz:                   All right. I see. So it’s like say, somebody who just wanted to know their APOE risk and their doctor added it to their LabCorp testing or something, that would be a direct measurement and that would not be as prone to the error that might come when you get a big gene panel.

Jeff:                     That’s right. That sums it up. Yeah.

Dr. Weitz:                   Okay. So let’s go into some of this genomic testing and how this can help with our risk for health and how this can help clinicians in evaluating and making recommendations to patients.

Valentin:             So for the ability to make recommendations, it’s really nice to have a platform that can be easily … you can easily navigate it, go to different categories, look up different types of information. One of the better systems out there, in my opinion, is the DSL Genomic Insights test or the Genomic Spotlight tests and loading it up into the Opus23 program. You could search for any SNP, any gene, look up different associations. There’s a lot of panel-

Dr. Weitz:                   Do you want to show us some of it and help us to understand how this can help with understanding various aspects of health?

Valentin:             Sure, sure. Absolutely, so can you see my screen right now?

Dr. Weitz:                   Yes.

Valentin:             Okay. So this is … I just loaded up the main program. This is a list of all the algorithms in the program. So this is where you can look up just about anything. Risk of prostate cancer. Risk of hypertension. Alzheimer’s. For example, for Alzheimer’s, early onset Alzheimer’s, there’s some SNPs associated with that. I don’t have that one. There’s all these … this happens to be my personal file, increased risk of-

Dr. Weitz:                   What are these SNPs? Can we see what they are?

Valentin:             Absolutely. So the early onset, I think this is the PSEN SNPs. Yeah. So PSEN1 and PSEN2 are these two genes for which some pretty good studies have been done showing correlation to early onset Alzheimer’s. So none of these … I don’t test positive for any of these. Some of these are kind of rare. I’ve had a few patients over the years, test positive for PSEN2. I think I had one PSEN1. So if you click on the actual gene, it’s really nice because it just turns into a pop-up, and you can look up all the SNPs in that particular gene and different agents that may help. Here, there would be S-Adenosyl-L-Methionine, SAMe. There’s some different … I think this is like thunder god, vine or something.

                                                Thunder god vine, Tripterygium wilfordii, it’s just a traditional Chinese medicine ingredient. Vitamin B9, folic acid. So it kind of tells you what works on that particular gene, which is nice in … then there’s some protein-protein interactions, so associations with this protein to other proteins. So here are all the other proteins out of a couple dozen, thousand that are associated with PSEN. So it allows for some more advanced analysis. If you click on one particular gene, let’s say somebody has a risk allele here, it would come up here and it would say GC. So one copy of the risk allele and associated with Alzheimer’s disease. So some of these have lots of associations, 10, 20, 30 different items on the agenda and others don’t.

                                                So it just depends which one. Here’s one. That’s a very nice one, increased risk of high cortisol when under stress. Do I get really stressed out? If I get really stressed out, yeah, it’s not very good. So I try to keep my stress levels in a manageable level. So for this algorithm, it talks a little bit about oxytocin, stress levels, the SNP. It shows you the risk allele, A. The client is AA, so that passes the algorithm test, so-

Dr. Weitz:                   So I’m confused. So this is saying that you do have risk?

Valentin:             Yeah, increased risk from too much cortisol went under stress.

Dr. Weitz:                   I see.

Valentin:             That happens because of this one SNP, I have both copies of the A allele under the oxytocin receptor, under this gene. We know what upregulates the oxytocin receptor, lactobacillus reuteri, that’s a big one. And also, life satisfaction, but you can’t put that in a bottle [inaudible 00:19:44]. I’m going to take two capsules of life satisfaction tomorrow morning. I’m going to be fine. I’m telling you right now, Ben. Dietary phosphorus restriction, that also upregulates, oxytocin receptor. Cold stress, hypothermia-

Dr. Weitz:                   Dietary phosphorus restriction. What a bizarre that is.

Valentin:             I know. That’s some really weird stuff in here. I usually focus on the tried and tested more common interventions. There are different acupuncture, C4, T2, different manipulations. There’s a phototherapy recommendations. There’s a lot of stuff in here. A lot of diet gene lifestyle interaction.

Dr. Weitz:                   So overall, your risk … let’s look at your overall risk now here for the Alzheimer’s thing.

Valentin:             For the Alzheimer’s?

Dr. Weitz:                   Yeah.

Valentin:             For that one, I would probably go into Argonaut. Argonaut is an app-

Dr. Weitz:                   So what is all this that you’re going into? Is this part of the basic panel or this is part of the more advanced Opus23 platform?

Valentin:             This is the more advanced Opus platform that kind of looks at disease risk and clinicians. There’s hundreds of clinicians around the world that use this. So here under the Argonaut app, we look at all the risk SNPs, right? So if I put in Alzheimer’s, all the Alzheimer’s associated risks along with the power factor, get brought up to the top. So here some of the higher risks for Alzheimer’s. Yep.

Dr. Weitz:                   Okay. Keep talking. The music came on and I just want to turn that off.

Valentin:             Sure, no problem. So for example, CYP1A1 is a very important gene, cytochrome P450 gene. It’s in the liver. It kind of acts like a bodyguard. When you walk into a bar, there’s someone that’s going to let you in or not let you in. So this guy likes to break down scary compounds that enter the body, CYP1A1. And it catalyzes many reactions, some of them involved in drug metabolism. Also, in the synthesis of cholesterol, steroids, other lipids. So if you have a high CYP1A1 activity or low CYP1A1 activity, you’re going to have increased or decreased risks of various diseases. So for example, here is one of the more common SNPs for it, the 6345.

                                                This is … if you have A allele on this one, I think you have a reduced CYP1A1 activity. So if you have both copies, which I do, you have an increased risk of biliary stones. Also increased risk of depression, GI inflammation, probably because the CYP1A1 enzyme really works to help detoxify things too. Pneumonia, acute respiratory distress syndrome, muscle, lean body mass, increased HDL, increased albumin, increased rectal polyps, all sorts of strange things. If you have the other copy, you have higher A1A1 activity, but then you have increased uric acid, increased maybe obesity, arm fat. Increased hemoglobin, increased hematocrit.

                                                Maybe your hemoglobin gets too high, maybe you need to donate blood. So there are pluses and minuses really to any one SNP or group of SNPs. It’s really nice to look at groups of SNPs because one SNP is just not going to give you all the information. Maybe there’s like two or three SNPs that really give you a more complete story. Sometimes there’s 20 or 30 you got to look at. There’s some companies that they look at thousands of SNPs, but usually, there’s one or two dozen that are really important for any one particular issue.

Jeff:                     Val, the way you’re sorting that is you kind of have your little Google search up there where you put Alzheimer’s in, right? So a practitioner or patient who has concerns about certain areas of health or family history, would that be a good place to start when you curate these SNPs?

Valentin:             Yeah, absolutely. So let’s say someone has some type of cardiovascular issues. They want to look at the heart disease. So I’d put in a CVD and all the top … some of the top CVD SNPs come in. Lewis-

Dr. Weitz:           Let’s say we do have a patient now. We have a patient, we measured his LDL and it’s high, and we did a coronary calcium scan, and he has … for his age, he has a significant amount of plaque. Now, what could this panel now tell us about how we would help manage that patient?

Valentin:             Okay, so somebody has a cardiovascular disease plaque. This is something that reduces the efficiency of endothelial function. So there’s going to be some endothelial dysfunction. I would look at some-

Dr. Weitz:           Meaning that if we’re going to support their endothelial function, we might want to support it more vigorously than we might otherwise?

Valentin:             Exactly.

Dr. Weitz:           And/or we might want to do more focus testing on endothelial function?

Valentin:             That’s right, that’s right. So if you look here, if I type that in, there’s a lot of nitric oxide SNPs, NOS2, NOS3, those are associated with cardiovascular issues-

Dr. Weitz:                   So if we’re going use specific supplements that support nitric oxide production, maybe in this patient who doesn’t do as well with producing nitric oxide, we might want to use a higher dosage.

Valentin:             Exactly. So for example, for NOS3, this is one of the main … this is the endothelial nitric oxide gene. This one, if you have a lot of red over here … I have patients who have, half of these are yellow or red, some of them are more important than others. See, this one has a higher power factor. So these two and this one, for example. So if somebody has a lot of nitric oxides SNPs, you’re going to want to increase it. How do you increase it? L-arginine. A Lot of people supplement with L-Arginine. I’m sure Citruline is here somewhere too. Let’s see here.

Dr. Weitz:                   Yeah, a lot of people have different opinions about the best way to promote nitric oxide reduction before using [inaudible 00:27:00] and they’re using … some people are using nitrates.

Valentin:             Right, exactly. So maybe the best researched one is L-arginine, omega 3s, vitamin C, trimethylglycine, resveratrol, ginkgo upregulates it. If you do a search of, for example for L-arginine. If you look at L-arginine, you can click on it and curate it. So curating it makes it end up in the final report. It’ll show you all the other genes that upregulate or upregulated or downregulated by L-arginine, and whether it’s an agonist or an antagonist. As far as nitric oxide, NOS3 specifically, we can look here. There’s a very long list of agents that have significant effects on a nitric oxide activity. So ginseng actually inhibits nitric oxide, NOS3, just as an example. Hydroxocobalamin inhibits it.  L-arginine upregulates it so does melatonin. So does an acetyl cysteine, not a surprise. Nigella sativa, black cumin. So, in looking at so many agents, you’re able to paint the bigger picture of exactly what you need. So here’s a GSR, this is a glutathione associated gene. And glutathione reductase is a very important enzyme in the steps of creating and utilizing glutathione, which is a cellular antioxidant. Here are the SNPs associated with it, and what turns on this GSR gene, right? NAC, glutathione itself, usually you can get in the form of reduced glutathione. A lot of supplements contain that. Vitamin B2, riboflavin, nicotinamide. Lots of different ingredients have been shown to upregulate GSR activity.

Dr. Weitz:                   Okay, so now Val, so this is using the Opus23 database, the more complicated program. Can you show us how using the DSL program using artificial intelligence, and that makes it a little bit easier to formalize for us to put into a workable platform for clinicians helping to manage patients, how that program is maybe easy to use than this one, because this seems very complicated.

Valentin:             Yeah. Yeah, this seems like a complicated program. The other ways to do it would be to use the Opus Explorer, which actually has a lot of the same apps that the full Opus23 program has. And then, there’s the genomic spotlight test, which is also very useful and people who don’t want to get into-

Dr. Weitz:                   So, with the genomics insight, that’s the middle level, right? This is the highest level one. Maybe you could take us to the middle level, the one that from DSL, and show us how that helps streamline some of this info to help with clinicians, say with conditions like you just mentioned, like let’s say we have a patient with Alzheimer’s or we have a patient with cardiovascular disease risk, how using that platform can help organize some of these genes and help us with managing patients.

Valentin:             Sure, sure. Absolutely. Let me try to sign in here.

Jeff:                     So what you’ll see is many of the same functions. So you won’t be limited to the pre-curated panels, but you’ll be able to use that search bar, and if you were searching for any disease state or any condition or SNP itself, you could still do that. So even when you look at the software and you see the pre-curated panels, you still have the ability and you can still see kind of the magnitude or how important the SNPs are. And you can still drill down in the same way and find out the same information of what the agonist and antagonists are. So all of it is there.

Valentin:             Okay.

Jeff:                     I think maybe if you show him kind of those pre curated reports, the report wizard, at the bottom there and let him see what the options are. Yes.

Valentin:             So we’ll look at the report wizard. So with this, the report wizard allows you to choose several categories. They’re actually 12 of them. So let’s say your patient is having cardiovascular disease, plaque, et cetera, issues. So maybe we’re going to choose inflammation and a cardiometabolic. And let’s say, there’s a lot of detox symptoms and genetic risks. So maybe we’ll choose some of the detox SNPs.

Dr. Weitz:                   Okay, sounds good.

Valentin:             And once you … you could choose a yes or no on any of these questions, do you want to include different maps that explain things, explanatory texts? Do you want to include all the SNPs in any program or just the ones that are risk … so after you make all these selections, you run the wizard and voila, there’s a full report that comes out. This is the Genomic Insight Opus Explorer report, and it reports for detox, inflammation and cardiometabolic, these three categories that we chose.

Dr. Weitz:                   Okay, cool.

Valentin:             And it explains a little bit about the data, probabilities and then, it gets into understanding the report. Green is good, that’s a benefit. Yellow and orange are not as good. Two pluses in red, that’s both copies of the risk allele. So that’s going to be worse than maybe just having one copy usually. And then, it gets into the detox section. So here’s the detox section. Here are some of the genes and SNPs. So this, for example, AHCY is a gene, and here are the three main risk SNPs for it and the associated methylation issues, homocysteine, autism, et cetera, et cetera.

Dr. Weitz:                   So for example, if this patient, let’s say, I ran this panel and I also did some lab tests and I saw that their homocysteine was high. This is now explaining one of the reasons why your homocysteine is so high is because you have these specific genes that’s going to tend to increase that likelihood. So therefore, we might have to use a higher level of, say, specific supplements that help to lower homocysteine than we might have to use otherwise, for example, right?

Valentin:             Exactly. Yeah, so it would make you pay attention to homocysteine, cardiovascular issues more, especially if you have symptoms and you tie them into genetics and you also tie them into blood labs like cholesterol, blood sugar, et cetera, et cetera. Here’s some other genes. CBS is another methylation associated gene. A lot of states there.

Dr. Weitz:                   What about CBS? Tell us about CBS for a minute here.

Valentin:             Okay, here is the CBS gene, cystathionine beta synthase, and this is kind of like the beginning of the transsulfuration pathway. It provides instructions for making CBS. Begins the transsulfuration pathway and provides groups needed for detox, protecting your brain, neurotransmitters, modifications to certain hormones, making glutathione. This can be blocked. Let’s say you’re taking aspirin, certain NSAIDs can block CBS activity. CBS needs P5P. That’s the activated form of vitamin B6.

Dr. Weitz:                   Okay.

Valentin:             It’s called Pyridoxal 5 Phosphate. A lot of supplement companies, they put in P5P into certain supplements, and one of the benefits of it is for methylation issues, which is what CBS involve-

Dr. Weitz:                   Right, so if I’m say now picking a supplement to help lower homocysteine levels, which typically is going to include B6 and B12 and folate, I’m going to make sure, I want to pick one that has the P5P form of B6 in it, because that would also help us with this genetic tendency.

Valentin:             That’s right. That’s exactly right. And if you actually … if we go to the CBS gene, so if we go to the SNP navigator briefly and type in CBS, here’s the actual gene, we can look up … Here are all the risk SNPs for CBS. So you can see here power factor very low. So this particular one, not really that big of a deal that I have a risk SNP in it, but for this one, it’s higher and that one is not. So basically I have one heterozygous risk SNP for it. So it’s not like sound the alarm kind of an issue.

Dr. Weitz:                   Now in your case, CBS is not that big of a deal, you’re saying, right? Because-

Valentin:             Not as big of a deal.

Dr. Weitz:                   Okay.

Valentin:             For some people there could be some serious-

Dr. Weitz:                   I see. Okay.

Valentin:             And over here you can see the agent expression fingerprint of CBS. So all the different agents that maybe can increase it. And one of them is P5P. Of course, the regular vitamin B6, just vitamin B6, Pyridoxine. Betaine or trimethylglycine has also been shown to improve methylation issues and actually upregulate the CBS gene and protein function. Interestingly, high testosterone levels has been shown to inhibit CBS activity. So people who are taking testosterone supplementation and people who have genetically high testosterone and DHT and whatnot, you might want to take a little extra P5P just because it might not be working as well, because that’s what high testosterone does.

Dr. Weitz:                   Interesting.

Valentin:             Yeah. So going back to this gene, there’s the COMT gene. Very, very famous, one of the top … between this one and APOE and MTHFR, I guess those three, everyone wants to look at those first, right?

Dr. Weitz:                   Those are the three big stars.

Valentin:             Yeah, and they are. They are important. So COMT is just … it works in so many levels, it’s very fascinating gene and the associations, if you have the low activity allele, that’s the Met allele, that’s because the protein that’s … I should say the amino acid that’s coded in that location ends up making methionine. If you have a different letter or nucleotide in there, then it makes the other one, which is valine or Val. So it could be Val or Met ValMet is what they call that SNP. So if you have the low activity version, you don’t break down dopamine as much, so you have higher dopamine, you can get stuff done better-

Dr. Weitz:                   So I’m confused, when I’m looking at this. So I see this SNP, it says the risk is C and then the type is R. R stands for what?

Valentin:             R stands for risk and B stands for benefit.

Dr. Weitz:                   Okay, and you are the TT, but I thought the risk was C, so you’re not at risk or you are at risk.

Valentin:             For this particular SNP. I don’t have … it says here UTT.

Dr. Weitz:                   What does that mean?

Valentin:             The outcome-

Jeff:                     That means the alleles found was going to be a T and a T and not a C.

Dr. Weitz:                   Okay.

Jeff:                     So it’s not-

Valentin:             Yeah, so there’s no issue.

Jeff:                     So this report shows a high functioning comm T because there are no aberrations here. So the risk alleles do not show up in any of these SNPs.

Dr. Weitz:                   Okay. So why does it say R for risk?

Jeff:                     Just tell it … because some are benefits and then, some are risk.

Dr. Weitz:                   Okay. Okay. Okay.

Jeff:                     Sometimes it’ll be green and it’ll be a beneficial SNP. Some SNPs that you have actually work in your favor.

Dr. Weitz:                   I see.

Jeff:                     This is just telling you that that C allele is the risk and then the result is a T and a T, so-

Dr. Weitz:                   So you don’t have that risk, so it’s not a problem for you.

Jeff:                     Right.

Dr. Weitz:                   Okay. I got it.

Valentin:             If you did, if this allele were the risk allele, then the patient would have an increased risk of worrying about things. So anxiety and also increased, interestingly, suicide risk, high cholesterol, increased type two diabetes stroke. So there are several problems with it. However, reduced risk of other issues. Schizophrenia, reduced risk of pancreatic cancer, improved executive function.

Dr. Weitz:                   Okay, you know what-

Valentin:             A lot of differences.

Dr. Weitz:                   Let me ask you to cut to the chase. Let’s say I’m a clinician and we started off by saying we have this patient who has cardiovascular risk. So now based on the genetics that we’ve run so far, what do we know about how we’re going to help manage this patient with cardiovascular risk differently? We had the thing about the homocysteine. Any other things that we can glean from this panel? Just in general, all the genes that come up for managing this patient with cardiovascular risk.

Valentin:             Sure. So you would go to the cardiometabolic panel. Okay, let’s go to … so here are the cardiovascular genomics.

Dr. Weitz:                   Okay.

Valentin:             And out of all of these, it looks like, let’s say the patient has a high level of ACE SNPs. ACE is an Angiotensin-I-converting enzyme. So people who have one, especially two copies of this particular SNP, RS4341, you’re going to have more problems. RS4343 is like lock stepping with this one. So if you have a problem with this one, you have a problem with this one as well. See, you have one risk allele here and you have one risk allele there-

Dr. Weitz:                   We know that the ACE inhibitors are used to control blood pressure. So I guess there’s going to probably be issues with blood pressure.

Valentin:             Exactly. So hypertension is going to be more of an issue for this particular patient and let’s say-

Dr. Weitz:                   So does that mean for this patient we want to use an ACE inhibitor or an ACE inhibitor wouldn’t work as well?

Valentin:             Well, it depends on the level of hypertension. So if this person has cardiovascular disease, there’s basically three levels, right? One, the patient has cardiovascular disease, but there’s not really any hypertension or there’s some or it’s very high.

Dr. Weitz:                   Okay.

Valentin:             That run into issues with really, really you need to do something now. It depends what level you’re at. It depends on the patient. Some patients do not want to take pharmaceutical drugs. So you have to look at alternatives.

Dr. Weitz:                   So let’s say this patient does have elevated blood pressure and they have this ACE SNP, and let’s say they don’t want to take an ACE inhibitor, which would normally be recommended or not recommended for this patient. What else could we do? Are there specific nutritional recommendations worked into this software?

Valentin:             Yes. Yes, there are. So if you scroll to the bottom, there’s going to be a list of agents based on the cardiovascular and the detox, the three areas that we chose, and here are the top natural products that affect the genes for which this patient has risk SNPs.

Dr. Weitz:                   Okay.

Valentin:             So the number one, essentially, a natural agent based on the categories we selected is resveratrol. And the number two would be omega 3 fatty acids. And it just goes down the line, and if you look at these, almost all of these are going to be associated with the three categories we chose. Was it cardiovascular, the detox. So this is going to comprise a part of the treatment plan. Another nice part of using this Opus Explorer program is being able to actually have recommendations made. So I usually use the other one, but we could try to see if I can get it into here. Here are the natural products.

                                                It’s either natural products or the other one. Yeah, it’s this one. So product advisor. So what is product advisor? It takes the top recommended supplements in the Designs for Health catalog and checks it. And basically, there’s a type of an AI system where it pulls all the information from a different database and shows you how appropriate it is. So mitochondrial NRG has a very high rating for this particular patient based on a full genomic analysis and pulling out different SNPs and kind of does the work for you, right? BioFizz Immune, Isoquercetin, zinc, vitamin D, vitamin C, all the risk SNPs, all the genes that have the risk SNPs are … you’re probably going to be assisted by these natural agents.

Dr. Weitz:                   Okay.

Valentin:             And there’s an evidence basis and there’s an indication basis for all of these supplements. So it kind of helps you figure out what to give someone. There’s Migranol, Curcumin, magnesium, Feverfew, and these are just the top six. You could pick the top 10, top 16, and it will use some precision medicine algorithms to help you decide a supplement.

Dr. Weitz:                   This is part of that Genomic Insights that is offered by Diagnostic Solutions?

Jeff:                     That’s correct. This is what comes with the Genomic Insight panel. So when you … you don’t get really a static report, you can print one of those pre-curated reports out, but you’re getting access to the software with all of this information with your result.

Dr. Weitz:                   Okay.

Valentin:             So it tells you … I went back to the report that Jeff was discussing. So it tells you all the different ingredients. BroccoProtect is a supplement, right? Discusses exactly why that’s good for you because these are the top 10 recommended products, they’re going to have discussions on all of them for this particular patient. And then, you get into a section called drug interactions. So these are all the different drug interactions available in the program-

Dr. Weitz:                   So this is saying if the patient consumes a lot of caffeine, they might have a higher risk of a heart attack.

Valentin:             That’s right, because they just can’t break down caffeine as well, because they have this C allele in this particular SNP that’s in the CYP1A2 gene, which breaks down caffeine among other activities that it has. So, here’s another drug, cisplatin, right? Risk of tinnitus. Fluorouracil, a morphine, better response to pain relief drugs. So people who have one or two copies of the A allele, they have really good response, so they may not need as much morphine. And I can attest to that. I had a couple surgeries and if they give me too much morphine, I’m just going to throw up about a dozen times after. So that totally makes sense.

Dr. Weitz:                   Whereas maybe if you had some autoimmune disease and they were managing you with methotrexate and we saw your liver enzymes go up, we might want to talk to your prescribing physician that maybe for you methotrexate might be a problem compared to other medications.

Valentin:             Exactly. Exactly. That’s pretty much the full report.

Dr. Weitz:                   Okay.

Valentin:             It’ll go into any three categories of those 12, and with the genomic spotlight, there are eight categories that it’s been condensed to. We haven’t looked at that one yet. So this is the mid-level, pretty good analysis. You can look at multi SNP macros. This is the same thing as the algorithms. So if you click on this, you can sort the page kind of like in Excel.

Dr. Weitz:                   So what is this telling us about aging here, significantly, younger, and healthier-

Valentin:             Yeah, the algorithm is a kidney function true, and the repute is bad. So that means that I have a risk SNP and there’s the risk SNP and I would have an increase in creatinine issues. So for an individual who has the T allele, his or her creatinine is approximately half that of somebody four to five years younger who does not carry it. So these algorithms are really useful. Here’s an antioxidant genotype, group one or group two. This can tell you whether or not you should put patients on zinc, vitamin C, E, zeaxanthin, astaxanthin, lutein, all these different supplements.

Dr. Weitz:                   So what is this saying now about zinc supplements? Explain this here.

Valentin:             Sure. So for AMD group two, basically, if you have risk alleles in arms two, which is just one gene and CFH, which is the second gene, these are the really big vision associated, macular degeneration associated genes and SNPs. If you have a lot of risk alleles in your ARMS2 gene, you need more zinc, and if you have no risk alleles in ARMS2 and you take a lot of zinc, it’s actually going to double your risk of age-related macular degeneration. It was a big study done with 3000 people and after seven years, your risk of AMD doubles. If you take a lot of zinc, but you don’t have any ARMS2 risk alleles.

Dr. Weitz:                   Okay.

Valentin:             And then, if you have a lot of CFH risk alleles, then the antioxidants help more, lutein, betacarotene, astaxanthin, zeaxanthin, vitamin C, vitamin E, et cetera, et cetera. Yep, so that’s a very interesting one.

Dr. Weitz:                   So, this is you and you’re at … well, you need to reduce your intake of zinc potentially or not take extra zinc.

Valentin:             Right, right. Not take too much. Of course, this is a lot more important in older individuals and it’s especially important if someone has a personal or a family history of macular degeneration.

Dr. Weitz:                   Right, and look at all the zinc, everybody has been taking the last three years.

Valentin:             Exactly. So that zinc can be great for you, okay for you or not so great for you, just depending on the situation.

Dr. Weitz:                   Interesting.

Valentin:             Just so you know, I have my patients temporarily take lots of zinc, especially if they have the flu or COVID or something.

Dr. Weitz:                   Right.

Valentin:             They take 100, 150 milligrams a day. It’s not a problem on a temporary basis, a couple of weeks.

Dr. Weitz:                   Right, but you know how many patients are still taking the same amount of zinc that they started taking in 2000 because they’re still worried.

Valentin:             And that’s why we do all this stuff. That’s why we’re looking at all this. Here’s a gluten sensitivity one. This is a HLA-DQA1. So this particular SNP is a very, very significant, I’ll tell you all the different associations that it has. Lupus, multiple sclerosis, type one diabetes, Sjogren’s, autoimmune hepatitis, Graves disease, Hashimoto’s, all different types of gluten associated issues. So I have one copy of this. It doesn’t really matter if you have one or two. You’re still going to have the same risk. You’re going to have an increased risk of all these autoimmune diseases with it. That’s an important one. There are several of these. There are several-

Dr. Weitz:                   So that might be an interesting one, let’s say the patient does have Hashimoto’s which means autoimmune hypothyroid, and that person, it needs to be avoiding gluten, whereas maybe somebody else who has thyroid issues doesn’t necessarily need to avoid gluten.

Valentin:             Exactly. So it’s very important to know what you need to do to maximize outcomes. So you can’t do everything. You can’t take all the supplements. You can’t eat all the foods. There’s just not enough time and space, so you’re going to have to make judgment calls, and judgment calls are fun for some people and horrible for others. I was talking to this one guy, about 75-year-old patient of mine, and we got into fruits and vegetables, which we really didn’t get into in previous appointments. His wife was there with us and we were discussing whether he eats fruits and vegetables and he goes, “No, I just don’t like vegetables.”

                                                So, I found out … I thought I did a pretty good intake at the beginning, but after two or three meetings with this guy trying to figure out how to help him having problems, I realized his vegetable intake is he probably eats like half a serving of fruits and vegetables per day. That’s his intake. So then, I got into the why. Why are you doing this? So he explained that he doesn’t like them, he hates them. So I found out one, he was a super taster and two, his parents force-fed him various different bitter vegetables, I’m sure when he was a kid. So he kind of has fruit and vegetable PTSD. Maybe it’s called PTSV, I don’t know.

                                                So for this type of person, I use the Ryan technique. I have a friend, Ryan who has the same issue. So one day we sat down, me and my good friend, Ryan. And we picked six vegetables that he doesn’t absolutely hate. He doesn’t like any vegetables, but he will consume these six vegetables. I forgot what they were, carrots, whatever. There were six vegetables. Obviously, corn is not a vegetable. White potatoes are not a vegetable and even though he had some good ideas, I’m sorry, President Reagan, ketchup isn’t a vegetable. Even though it’s got a lot of benefits from the tomato part, there’s just a ton of sugar in it.

Dr. Weitz:                   Right.

Valentin:             People who were trying to reduce carbs should probably not have a lot of ketchup. So we got into the … I think we got five, I don’t even think we got to six. We got five vegetables that he will maybe eat once a week or something. Then, we gave him some type of extract. I think it was the designs for health, red-

Dr. Weitz:                   Paleo Reds. Yeah.

Valentin:             Yeah. Paleo reds, paleo greens. We got them that.

Dr. Weitz:                   Yeah. Yeah, that’s a good way to increase the range of vegetables. We do that a lot too.

Valentin:             Yep, as you can see here, there’s a lot of pharmacogenomics as well. So CYP2D6, CYP2C19. It’s important to know if one of these enzymes works. In fact, I heard everybody-

Dr. Weitz:                   What’s sad though is how many patients are being prescribed pharmaceuticals and does anybody ever screen this stuff to find out if that pharmaceutical is liable to be effective or have side effects for them?

Valentin:             So for example, let’s just take Paxil. Anyone who’s taken any of these drugs, type it in, go to Wikipedia. What’s Paxil? It’s SSRI and then, even though you don’t know much about somebody’s … not you, but just the average person, maybe they don’t know much about this, but you could always go to the interactions and the pharmaco … anything with pharma, it’ll explain how it is broken down. So from here, we can see that this interacts, so Paxil interacts with your liver enzymes, and you can see here CYP2B6, strong inhibitor. The weak ones, it’s not as big of a deal, but this is. Some of these interactions, so if something you’re taking is a strong inhibitor of something, then you can go back to your list and see if you have that.  And if you have that variant, then it’s going to basically turn off that enzyme. So it’s important to know that because that could have other effects. So it’s nice to be able to crosscheck. That’s why it’s good that your doctor or practitioner, whoever the patient works with, has access to this type of metagenomic data.

Dr. Weitz:           Is there a way that you could just put in the five medications as patients taking and find out if there are genes and interact with those medications?

Valentin:             Currently, there’s nothing like that going on, although I am working with a few people on that type of a situation right now, but I can’t discuss it too much. Yeah, there’s some of that in the works.

Dr. Weitz:           Okay.

Valentin:             Even in the Opus program, you can type in … let’s say, pick any medication.

Dr. Weitz:           Paxil, you said.

Valentin:             Paxil, so let’s take a look at Paxil. So right away you’re going to have CYP2D6 and HTR2A. So both of them are affected. I do a Paxil search. Women who have the G allele were more likely to be given the cold shoulder by men. That’s really funny. Paxil increased adverse effects. So there’s really weird things with Paxil if you have certain genetic variants. So yeah, that’s one way to look at it and here’s the CYP2D6 one. We could look up Paxil here. Drugs metabolized by CYP2D6 is huge. You think, “Oh, it’s not that big a deal. It’s not even one, it’s two,” right? And it’s not A, it’s D and it’s not even one, it’s six. So it’s got to be not that important, right? CYP2D6 is really important. It’s probably one of the top three liver enzymes for drugs and all sorts of other issues.

                                                CYP2D6, slow metabolizers, a lot of problems, if you don’t know what you’re getting yourself into. There are some people that are like, I can’t take this, I can’t take that. I have an issue with this, issue with that. These patients usually have one or two big risk alleles in one of these liver enzymes. That’s why they can’t take anything. That’s the reason. So for this particular SNP, double reduced metabolism, that’s this … and if you take this one and we throw it into the nice government-sponsored SNP analysis NIH program, we could even see how common it is. This says 0656 SNP. It’s like, it’s not too common. Let’s see here.

                                                The allele in Europeans is two and a half percent. So like 5% of Europeans have it. You can’t find it in anybody in East Asia, for example. It’s just not there. South Asia undetectable. In African populations, a little bit, pretty rare. So this is basically a European or Caucasian population-based risk SNP. Now, it doesn’t mean that if you happen to be Asian or African or African-American, it doesn’t mean you’re out of the woods, because they have other risk alleles in the same gene. So it’s like if you’re from this part of the world, this one risk allele is what you have to look at, but if you’re on this other part of the world, then these other three are what you have to look at. It’s nice that the program has all of them in there.

Dr. Weitz:                   All right, let’s work on trying to bring this to a close. What are maybe some of the final messages or some of the important things? Unless there’s anything really pressing that you want to cover?

Valentin:             Jeff, you go ahead.

Jeff:                     So I think you can see just how deep into the weeds you can get. And that is cool, that’s good but I think using the report wizard helps you. He put three reports together, which made it a little longer, but it will show you in the gene what the risk SNPs are, and if you have those risk SNPs and then, you can kind of dig in from there and see what natural agents or even products are helpful for that, right? So you can go as deep as you want to. When you use our genomic insight testing, you have access to this indefinitely. So you have all of your SNPs. At some point, you may want to come back and look at a different disease state or risk.

                                                So really I think the level of information is kind of vast. So it’s good to focus in maybe on with a patient, what is your primary concern? What is your health risk? What is your family history? And not really go into the weeds. So we give you the option to do that. We also give you the option to go way into the weeds if that’s what you want to do.

Dr. Weitz:            Okay. Okay. All right, cool. So practitioners who want to start using some of this testing, they can go to diagnostic solutions and sign up for an account. And then, if they’re not a doctor, but they still want to use a version of this, what is that version called?

Jeff:                     So that version goes through Designs for Health, and that is going to be the Genomic Spotlight.

Dr. Weitz:            Okay.

Jeff:                     Designs for Health will probably guide them to a health professional. We can also do that as well. So if they go to diagnosticsolutionslab.com where they reach out to us, we can help them find a practitioner who specializes in this. I can’t imagine that you would want to navigate this without … you have all of this genetic information, but you also have to compare that to the phenotypic response that you’re seeing as well. So I think you really need a practitioner to help you with that. And Diagnostic Solutions Lab also helps practitioners with the results too. So we do it with the GI map, we do it with Genomic Insight. We help you understand how to navigate the software and how to get the best use out of it. So we’re available for that support as well.

Dr. Weitz:            Currently, through Diagnostic Solutions, is there one report or several reports approximately what is the cost?

Jeff:                     The cost, let me look at this. I haven’t looked at this in a while, but the …

Dr. Weitz:            I want to say somewhere around 300 bucks or something like that.

Jeff:                     It is 329. The cost is 329, but you’re getting your full catalog of SNPs here, right? So I mean it’s really a great value. Again, those are options that you can choose and because you have this data indefinitely and you have access to this file indefinitely, if cardiometabolic is your primary concern right now and later on it’s cognition, you could come back with the patient in a year from now and then, curate the cognition SNPs. In addition to that, you can use the search bar or look at … you can type in macular degeneration if that’s something you’re interested in.

                                                So really there’s lots of ways to use it. You can use the pre-curated panels or you can use … or if you just want to know a specific SNP, if you’re researching that SNP or that SNP comes to mind or that’s something that you’re interested in, you can look up that SNP directly. Again, you’ll see the risk allele, if it’s … what type it is and then, what the patient actually has, whether it’s heterozygous or homozygous or no risk allele.

Dr. Weitz:            Okay, and this is a saliva test, is that right?

Jeff:                     It is a saliva test, that is correct.

Dr. Weitz:            Okay, Awesome. Well thank you so much guys. And to find Diagnostic Solutions, what’s the website, phone number?

Jeff:                     Yep, Diagnosticsolutionslab.com or 877-485-5336.

Dr. Weitz:            That’s great. Thank you so much.

Jeff:                     All right, thank you.

 


 

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

 

Mark Newman discusses Hormone Metabolism and Testing 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

1:48  Dried urine testing or DUTCH testing uses a dried sample for convenience, which is a big advantage over the other leading type of urine hormone testing, which is the 24 hour urine test that requires carrying around a jug of urine that you keep in the refrigerator all day.  This is very inconvenient and you lose the the changes in those hormones levels, esp. cortisol, that vary throughout the day using a 24 hour sample.  The dried urine test you collect samples throughout the day so you can look at the cortisol pattern, which correlates with what is seen on saliva in studies that have been published.  And the urine testing of hormones allows you to see the metabolites of estrogens and androgens that you can’t see on blood testing.  And there is a DUTCH complete test that includes markers in urine for melatonin and B12 and B6, etc. that allows us to see a fuller picture of the hormone story.  For example, this complete testing is helpful if you have a patient who has fatigue you can find out if it is related to testosterone or cortisol or B12.

4:57  On the other hand, dried urine testing does not allow you to measure SHBG, which can be measured through blood, such as when a woman is on birth control and this drives up her SHBG, which drives down her free hormones. Urine testing is also not a good way to measure thyroid hormones. Also, if your kidneys are not functioning well, then you are not excreting urine as well as you should and this can impact urine testing. Also, saliva has some advantages for the cortisol awakening response (CAR), so DUTCH plus includes saliva for the first two samples of cortisol, since for the CAR you need an instantaneous sample when you first wake up within the first five minutes.  DUTCH uses a cotton swab that soaks up saliva instead of having to spit into a tube like other labs use and fill it with 3 ml of saliva after waking up without rinsing your mouth and without drinking any water and for most people this takes 15-20 min, which negates the value of the CAR test.

8:50  Estrogen metabolism.  Urine testing allows for monitoring of estrogen metabolites that you can’t get with serum testing and this can give us some information about how the person processes their hormones and also provides some information about estrogen related cancer risk.  Mark explains that the first thing to consider is the woman estrogen deficient or do they have estrogen excess. And there are three doors of metabolism that estrogen can go through, including the 2 hydroxy, the 4 hydroxy, and the 16 hydroxy estrone pathways and the 16 got a lot of attention because the 16 hydroxy estrogen is more active proliferative estrogen if this pathway is used more it can exacerbate estrogen dominance.  In terms of breast cancer risk, there is more focus on the 4 hydroxy than the 16, since the 4 has the unique ability to make a reactive quinone.  The 2 pathway is clearly more favorable in terms of cancer risk.  If reactive quinones are produced, then need to be detoxed and methylation plays a role and glutathione and resveratrol can upregulate the quinones.  If the quinones are not detoxed, they can damage your DNA.

                                           



Mark Newman, MS is a recognized expert and international speaker in the field of hormone testing. Mark spent nearly 25 years developing and directing urine, blood, and saliva-based hormone testing along with other biomarkers like organic acids. His unique experience led him to pursue a revolutionary way to test hormones; so Mark began his own lab, Precision Analytical Inc., to create the latest innovation in hormone testing, the DUTCH Test® (a Dried Urine Test for Comprehensive Hormones). In pursuit of the most accurate, evidence-based testing and best practices, Mark has co-written multiple peer-reviewed research papers and abstracts, highlighting the accuracy and clinical utility of dried urine hormone testing. Mark’s primary educational goal is to find and communicate truths about HRT monitoring to help providers care for their patients. He understands that each form of testing has its own strengths and weaknesses, which is why he encourages clinicians to follow the evidence even when lab testing isn’t clinically helpful. For clinicians to learn more about the DUTCH test, go to DUTCHtest.com Patients can find a referral to a DUTCH Lab provider to order and interpret the testing for them.

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

 



 

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 we’ll be having an interview with Mark Newman about hormone testing and metabolism. Mark Newman is a recognized expert and international speaker in the field of hormone testing. Mark spent nearly 25 years developing and directing urine, blood, and saliva-based hormone testing, along with other biomarkers like organic acids. His unique experience led him to pursue a revolutionary way to test hormones so Mark began his own lab, Precision Analytical, to create the latest innovation in hormone testing, a Dutch test, which is a dried urine test for comprehensive hormones. Mark has also co-written multiple peer-reviewed research papers and abstracts highlighting the accuracy and clinical utility of dried urine hormone testing. Mark’s primary educational goal is to find and communicate truths about hormone replacement therapy monitoring to help providers care for their patients. He understands that each form of testing has its own strengths and weaknesses, which is why he encourages clinicians to follow the evidence even when lab testing isn’t clinically helpful. Thank you so much for joining us, Mark.

Mark:                    Thanks for having me, Ben. Great to be here.

Dr. Weitz:            I’d like to just dive into the science of hormones and hormone testing, but I realize there’s probably some listening to this podcast who might not know what dried urine or Dutch testing is. So perhaps you can give us a short summary of what dried urine testing is and what are some of its advantages.

Mark:                    Sure. Yeah. The fact that we use a dried sample is simply for convenience. The main thing that we’re after honestly isn’t convenience, it’s information and data. I spent years doing urine testing where people would carry a jug of urine and you can get lots of interesting information.

Dr. Weitz:            That was a 24-hour urine test. Yeah.

Mark:                    Yeah. Lots of information, not lots of fun. And the main thing you lose though is those hormones, particularly cortisol that’s supposed to go up in the morning and down at night, if you get that pattern to say inverted, you lose that in a 24-hour collection. And so people often go to saliva for that. So after years of doing 24-hour urine and saliva, we wanted to find one easy way for people to get lots of information, and that’s what the dried urine test is is multiple samples throughout the day so we can look at that cortisol pattern, which we’ve published the data correlating that to the saliva pattern, and then we measure the aggregate of those samples to give essentially a 24-hour urine equivalent on all the things that you can measure in urine, like the metabolites of estrogens and androgens and all of those things. So it’s a really nice look at reproductive and adrenal hormones. It’s about as comprehensive as you can get on that front.

                                And then after we’ve built that base, then we just started adding things to it that speak to that story. Melatonin, B12 marker, B6 marker, and so on. Filling in the other pieces of that story so that we can tell as broad of a hormone story as we can because a lot of the symptoms that … If you have fatigue, maybe it’s testosterone, maybe it’s cortisol, maybe it’s B12. There could be a lot of different things related to that. So comprehensiveness is the name of the game for us, and that’s where the idea of the Dutch test came from. So that’s the shortest version I can give you of that I guess.

Dr. Weitz:            And hormones other than cortisol also vary throughout the day. So another reason for taking various samples throughout the day as opposed to serum where you’re just getting one sample is that the dried urine allows that as well.

Mark:                    Yeah. It depends on the hormone, but there’s a really old paper where they took some women and tortured them and measured their serum all day long. It was actually astounding to me how a woman’s progesterone would move during the luteal phase from five or six clear up to 30. It’s pulsatile so it bounces quite a lot. I don’t think they’re always quite that variable, but the data they had, it was remarkable and it speaks to the advantage of having something that collects over time. With our four samples, it’s 10 to 14 hours of your day represented. So those ups and downs get averaged out, and I think that that does have its advantages. And serum testing certainly is always going to be a tool that complements nicely I think what we do.

Dr. Weitz:            What are some of the disadvantages of dried urine as compared to other forms of testing like serum or saliva?

Mark:                   There are certain things you just can’t measure there. If a woman’s on something like birth control and her SHBG goes up, that’ll drive down her free hormones. We see that. So oh, you have less testosterone or estrogen than you otherwise would. But in that case, the root cause is a little bit more clear when you’ve got SHBG, which is blood. We always like to complement what we do with a thyroid panel and there are people trying to eke out thyroid in urine, but it really is just better measured in blood. It’s more comprehensive, it’s better researched. So in terms of information, what we do is a lot, but it is just one piece of what we do. If your kidneys aren’t functioning right, urine testing’s not a very good way to measure your hormones because everything we do is relative to creatinine, which you excrete as you should unless you have a kidney issue. And so in those cases, we would push someone elsewhere. And then about, oh, three, four years into this journey, the literature really started to speak to us that there’s a unique story that saliva tells about cortisol that urine can’t quite match, and that is the cortisol awakening response, and that’s why we developed the Dutch Plus.  So Dutch complete is four urines, but saliva’s story of cortisol has a little bit more unique value compared to urine. So we have the Dutch Plus where you do the same urine samples, but also saliva at waking, plus 30, plus 60, dinner time and bedtime. And what you really want to hone in on there is that waking within five minutes and 30 minutes later there’s a gap. And that gap has to be an instantaneous reading and an instantaneous reading, which you can only get out of saliva. And that gap acts as we call it like a mini stress test. So when you’re stressed, your body does this. When you wake, your body goes through that same biochemistry. And so measuring salivary cortisol right at waking and 30 minutes later gives you not only the diurnal pattern that we can see in our urine-only test, but it also gives you the cortisol awakening response or the CAR. And so that gets even more comprehensive, which again is why we have our Dutch Plus, which is just a little bit more information but it’s great for those people really wanting to focus on the cortisol story.

Dr. Weitz:            And one of the advantages, the tweaks that you’ve come up with for that test is that instead of having to fill up this tube with saliva, which by the way is a lot of stress for people, you just have to have these little cotton swabs that soak up the saliva.

Mark:                    Yeah. We weren’t really comfortable doing it any other way because the reality is when you’re doing these things, you get what other people are doing and check it out. And I grab one kit from a company that’s actually no longer in business so I don’t mind picking on them. But here’s your tube. Fill it up with three milliliters of saliva, waking up without rinsing your mouth without eating or drinking anything. Most people, it takes 15, 20 minutes, but that completely negates the value of the CAR because when you hit five minutes, now you’re in the middle of that ramp. So if it’s a 15-minute collection, then it just doesn’t work. And the reason they do that is practical, is that they’re getting the CAR. But they’re also going back into that same sample for progesterone, testosterone, and estrogen, which we think are … Especially estrogen and progesterone are better measured in the urine sample. And it just so happens that those little cotton swabs, which are great for cortisol, absorb progesterone, and so you cannot use them if you’re testing progesterone. So for us, it was a perfect combination of what actually works best but also fits in well what we’re doing with our other testing because you can collect those in 60 to 90 seconds, but that’s really key if you want to know what your cortisol is at a moment in time.

Dr. Weitz:            One of the more interesting aspects of dried urine testing for hormones has to do with the estrogen metabolites. Can you talk about the estrogen metabolites, phase one, phase two, and also where we are with the data in terms of what’s affecting our risk for breast and other estrogen-related cancers? I know that several years ago there was the two to 16 hydroxy estrogen ratio that seemed to be the big factor, and that’s fallen out. And I think it seems to be pretty clear that the two is the healthier one, but maybe there’s more focus on the four as being a risk factor. Perhaps you can talk about that whole issue.

Mark:                    Yeah. It’s a complex issue. When it comes to estrogen, question number one is what’s your status? Are you estrogen deficient? Are you estrogen sufficient? Are you estrogen excess? And for that, you can look at the whole family, but we hone in more on estradiol and to some extent estrone. And we found that the urine test is a really nice way to do that. And then as you mentioned, now we’re looking at the cascade of where does it go? And you’ve got those three doors of metabolism that the estrogen can go through. Two hydroxy, four hydroxy, and 16 hydroxy as you mentioned. 16 hydroxy got a lot of attention before the four hydroxy was really known in terms of what it was and what its mechanism of action was in terms of breast cancer risk. And the main reason for that is that the 16 hydroxy estrogen is just a more active proliferative estrogen.  So I guess you would say it’s more estradiol like your primary estrogen. It’s more effective that way than any of the other estrogen. So it actually hits the estrogen receptor more powerfully than the other metabolites. And in that sense, if you have a woman who’s high estrogen and she metabolizes it down that 16 hydroxy pathway, that’s going to give her a little extra punch, which is going to exacerbate estrogen dominance in terms of symptomatology and need for progesterone to counteract that and that sort of thing. So the 16 is by no means irrelevant but it’s actual play in terms of breast cancer risk, I don’t think is quite as significant as it was initially thought when there was this hyper-focus on just the two and the 16. Because you can move around the two and the 16 and people watch that for a long time. You can give people dim and you can tilt towards two. And when you’re doing that, you’re also impacting the relationships of those metabolites to the four hydroxy, which if you go way back in the literature when they started asking questions about that, we were a little bit later to the game in terms of the four hydroxy.  The four hydroxy has unique characteristics as well. So the 16 is unique because it’s strong as an estrogen. The four is unique in its ability to make a quinone. So that is the four hydroxy means your estradiol has a little hydroxy group on that phenyl ring, and then the four gives it two of them. And because there are two of them, they can create this little reactive group and that can create some problems in terms of damaging DNA.

                                So you’ve got this relationship between the two and the 16. The 16 is this strong estrogen, and then the two is more favorable in terms of its cancer risks. And then you’ve got the same dance going on between the two and the four, but for a different reason in that they both can create this reactive quinone and then that reactive quinone if it’s not detox … And that’s what we talk a lot about detox. Methylation, glutathione, resveratrol to upregulate quinone … There are a lot of different … Well, not a lot. There are a handful of ways to get rid of that reactive species, and if not, they grab onto your DNA. And it happens that the two will let go because it’s a weaker bonding, whereas the four grabs on pretty tight so it can rip a piece of your DNA off. And that’s where it’s thought that the carcinogenic potential comes from is that unique chemical characteristic of the four hydroxy.  So we want to know which of these pathways is favored. And there’s some good research showing that the two hydroxyl has a more favorable profile when it comes to risk of estrogen-related cancers like breast cancer, and that the four hydroxyl seems to be more of a bad actor in that whole equation. So that’s phase one metabolism. Which of these three doors are we preferring? And then there are things that you can talk about to manipulate that. And then once you make them, then one of the main pathways for getting rid of them is methylation. So hydroxylation is phase one and then one of the steps of phase two is methylation.

                                And so for me, when I test my estrogen metabolites on the Dutch test, I don’t methylate very well because I have a COMT genetic defects. I have a single nucleotide polymorphism that I’m homologous for, so I don’t methylate. So what I’ll find is that the ratio is usually two to one. You make the two hydroxy, it’s like 10, you’re going to get five of this. So 10 to five, 10 to five. Well, for me, if I’ve got 10 of this, I’m more down there at like two because I just don’t make that conversion very well. Even when I’m supporting methylation, it’s hard for me to make that conversion because my genes don’t do that very well. So what does that mean? It means those reactive species are not being protected very well by methylation. So it’s smart for a person like me to support things like glutathione because that’s another way that we can get rid of those things. But the first step is just figuring out what your profile looks like. Do I favor 16? Do I favor two? Do I favor four? And then do I methylate well?  And so we like to focus in on the two hydroxy, two methoxy for methylation because we found that’s the most reliable way to look at methylation is to see that conversion there. And we see some relationship there with things like genetic defects and if people aren’t supporting their methylation well enough, and that’s an important protective step. Not the only one, but it’s a protective step. One of the genetic studies show that when you have the genetics that favor four hydroxy and you have the genetics that disfavor methylation, and then there was one other … I think it was the SOD, which is one other detox. One, two, and three. Each of those as individuals wasn’t a big player in breast cancerous, but when you had all three, it was something like six or 12 times higher risk because it just opens up that channel for those metabolites to head in the direction where it’s believed that they cause problems instead of heading in the directions of safety through proper metabolism.

Dr. Weitz:            Do we know is there any relationship between estrogen metabolism and prostate cancer risk in men?

Mark:                   There is some research on that same mechanism for hydroxy estrogen. DHT of course plays a role so the androgen metabolism is important in that as well. Gosh, it’s been a while since I really dug into the research on the men’s side of it. If you go back to where those cells are coming from in terms of estrogen related cancers and things like prostate cancer, there are some parallels there. And so estrogen is not friendly towards prostate cancer. And then if you’re making the four hydroxy estrogens, all the more in terms of risk. But gosh, it’s been a while since I’ve read the studies specifically on that one. It does have value in men as well to have your metabolism heading in a more favorable way, which is why a lot of doctors will use things like diindolylmethane or indole-3-carbinol. Those supplements that really push down that two hydroxy pathway.

                                For me, I always give a little bit of caution for people on that as well in that when you look at the genetic data on the genetics that speed up to hydroxylation, you think to yourself, oh, that’s good. Speeding up two hydroxylation will be favorable, but it actually correlates with overall cancer risks that are higher in certain settings. And I think the reason for that is when you go two hydroxylation with estrogens, we think that’s good. But when you do the same thing with things like poly aromatic hydrocarbons, things that are environmental toxins, a lot of those can use that same enzyme. And when they get too hydroxylated, they become pro-carcinogens. Things that alter that metabolism I don’t think should be given out like Tic Tacs to every patient that comes into your office. We really want to know, does someone have a need for influencing their metabolism preferentially in a particular direction? And if not, then we want to use some caution there.

                                The other caution there is knowing that it’s not just moving. It’s like opening a little vacuum there. So if you have a person who’s on estrogen replacement therapy … We’re actually working on a publication right now showing that women who take dim, it changes their metabolism. Yes. But it also lowers those parent hormones. So if you’re thinking about a woman’s estrogen status, whether it’s endogenous or exogenous, you’re going to be lowering their estrogen status usually when you give dim, and that’s going to be a dose dependent thing. So again, we want to be aware of these things. They’re tools in our toolbox, but we also want to make sure that whatever profile a particular woman has that we’re catering to that in terms of her needs and not just needlessly treating everyone the same way because their individual biochemistry really matters.

Dr. Weitz:            That’s interesting. I’ve talked to practitioners who prescribe hormone replacement and automatically they think that they’re lowering the risk by every single woman that they put on hormones, they automatically give them dim, they automatically give iodine, they automatically give them one or two other things.

Mark:                    Yeah. And there’s some logic there. But I think if you have a woman who’s already a big two hydroxylator and you’re using conservative doses of estrogen, then that may not be in her best interest. Money matters too. So just buying supplements that a person’s body is already shoving in a particular direction may not be something that they need. And the truth of the matter is there aren’t a lot of studies on that particular intervention and what happens in terms of outcomes. There’s an extrapolation there in terms of saying, hey, this profile seems favorable, this thing leads to this profile, therefore this thing leads to these outcomes. Those dots have not been connected in a strong way. And so I think it’s good to just be thoughtful as we address those things. And again, to also know if I put a woman on a patch, then I put that same woman on a patch with dim, it’s a lower dose patch when most women effectively. Because again, you’re opening up that channel of detox. So more than anything, just to be aware of those relationships and to know what’s going on as you’re making intentional alterations to someone’s biochemistry is really important.

Dr. Weitz:            And also a very strong argument for why to test versus guessing, because I’ve also talked to practitioners who say, well, I don’t need to test. I can just tell by how the woman’s feeling.

Mark:                    Yeah. And you can guess and you’ll guess right a fair amount. But I’ll tell you, when you test, you get surprised by someone often. I might put someone on dim and I might test them and then realize, oh, they’re a really, really poor methylator. Well, when you think through this, when you create hydroxylated estrogens and then you don’t methylate well, and then you load that up even more, that may be counterproductive. And knowing that that woman needs more methylation support because of her unique profile is really important. And the thing that I always caution people when you’re talking about HRT … And it’s conventional wisdom, you go to NAMS, you run around with people that are a lot smarter than I am, and most of them say testing is a waste of time. But when we test different people and they end up absorbing at different levels, and you stop and ask yourself, now, hold on, what’s going on with these women? So I pause and I look and I say, okay, let’s stop and look at the placebo studies for HRT. And when you look at hot flash studies for HRT, half of the impact is from placebo.

                                So if I put a woman on nothing. I say, “Hey, here’s your estrogen cream and it’s nothing.” A lot of them will feel significantly better. And then you pause and ask yourself, how did the placebo arm work in bone mineral studies and bone density? You cannot fool the bone with placebo. And so if you have women and all you’re tracking is that they’re feeling better, it’s important. But a lot of times you go to this functional medicine doctor, they’re brilliant doctor, so they’re fixing the gut, they’re fixing all these things. If you give an insufficient dose of estrogen, most of those women are going to feel better doing really positive things in their lives. But if seven years later they have osteoporosis and 15 years after that they break their hip, that’s not a net win on that front. And so that’s where I think it’s really important knowing that from woman to woman on the same therapy, you can get significant difference in terms of what their therapy does in terms of absorption in their actual levels of estrogen. That’s what we’ve been pushing on that front a lot is I think the urine test is a really nice way to monitor not only someone’s baseline endogenous levels of estrogen and their metabolism, but also to give an idea of systemic absorption of estrogen to make sure that what you think you’re doing, you’re actually doing in terms of adequacy of the therapy.

Dr. Weitz:            Let’s continue with that. I want to footnote. I want to go back and ask you about the … Well, let me ask you real quick. The two, four, 16, it seems like a lot of the testing focuses on the hydroxyestrone or the E1. Does what goes for the E1 is the same thing, go for E2 estradiol, which is the hormone most of us are more focused on?

Mark:                    Yeah. The actual impact of, hey, what’s giving someone cancer? They both play into that and you can tease into the literature and see is there a stronger impact of one or the other. What we find is that the estrone is the easiest to measure really well to see what someone’s preference is. Those enzymes, those four-hydroxyestrone four-hydroxyestrodial are different up on this end of the molecule. And then down here you have the four-hydroxylation going on. You have the methylation going on. So they’re very, very similar molecules in terms of what’s going on with phase one and phase two. But it just so happens that the estrone metabolites are at significantly higher levels. So they’re easy to measure really well. In fact, for us, for the four methoxy … Oh gosh, we’ve designed tests for that six, seven, eight different ways and looking at the data, we just don’t feel like it’s strong enough data for us to lean on that in terms of just asking the question, how is my patient methylating I’ve seen a handful of labs over the years add some of those metabolites and then take some of them back when you start to realize the data’s not lining up as well as it should. So for us, we’ve really leaned into what’s most reliable and what seems to correlate best to the actual data that we’re looking at.

                                I’ve seen a number of cases where people have brought to me and said, hey, listen, I’ve got a patient who’s got four hydroxyestrin and four hydroxyestradiol and one of them been methylated really heavily and the other one’s not methylated at all. What do I do? And as an analytical guy, my response is, it’s not likely that that’s biochemistry. It’s most likely that both of those methylated products are very, very difficult to measure. And so you get a little bit of noise and you’re down in that noise for us at an analytical level. And so the reliability of those values and the difficulty in the lab of measuring them well is probably more at play than someone who has some biochemistry where the same enzyme sees these almost identical twin molecules and methylates the crap out of one of them and doesn’t touch the other one. That doesn’t make a lot of sense.

                                And so when we’ve looked at all the metabolites that can be measured, we measure four hydroxy E1, we measure four hydroxy E2. But when it comes to asking a question of what’s going on with this woman’s individual biochemistry, we lean into those that have been proven to be the most reliable. And that’s a complex topic because different labs measure things differently. And I’m not here to throw stones at someone else’s methodology because I don’t get to look behind the curtain at what they’re doing. I just know that I’ve seen people learn lessons over time with some of those things as they’ve measured them and then realized that they’re very, very difficult to measure well at those really low levels, even using the really sophisticated methodology that we all have available in 2023.

Dr. Weitz:            Okay. So let’s continue into dried urine testing to monitor hormone replacement therapy. And this might be a good time to tell us about the paper that you published in the Journal of Menopause, looking at the efficacy of dried urine testing for monitoring women who are taking either compounded transdermal estrogen versus those taking FDA approved gels and patches.

Mark:                    Yeah. When you come into our world and you get educated on this stuff, someone like me is going to have a microphone and oftentimes there’s a lot of speaking with a lot of confidence, but there’s not a ton of data that’s been published in this area, and there’s a lot of extrapolating going on. And that’s been really a passion of ours is to get … Well first to interrogate our own views on these things. And they’ve taken shape over time as the data informs it, but to really get into the peer-reviewed literature. What does this therapy look like on not just our tests, but I’m also interrogating and evaluating. Because I used to run saliva labs. Looking at what these different products look like in all the different tests. And then what I like to do with that data once there is then overlay the clinical data that’s available with those products so that we can see which lab tests are speaking most true to the picture of what’s going on. And the biggest challenge in all of that is the compounded products don’t have any outcome data that’s in the literature. And so the best we can do is to extrapolate a little bit with that data.

                                So what we’ve done, which is not just one publication … That menopause one is a crescendo of several years worth of work, which is taking the most common products that we look at for estrogen and isolating the transdermal products and then looking at the relatively low doses, the medium doses and the high doses, and seeing what those patterns look like in urine in real time in a real data set. And so we published that data then in a couple of different journals, and then this aggregation of the data in the menopause article, which we’re super excited about. The way I work through it is our graph shows patch data and then gel data and cream data. And I start with the patch data because they’re the best characterized. So patches are really nice because one, they’ve been tested against hot flashes, vaginal atrophy, bone loss, all with placebo so they’re really well characterized.

                                The other thing that people oftentimes don’t understand about those products is they’re named after the delivery dose. So when you take a patch, it might have four milligrams of estrogen, it might have 10 milligrams of estrogen depending on what it is and all of that. But the naming of it is how much gets in every day. So a .025 patch has a whole bunch of estrogen and it delivers .025. And then when you go to .05 it delivers twice as much and .1 twice as much as that. So they’re really well characterized. And so we start with that data. And what we see is that women on no therapy that are postmenopausal, of course, end up in that postmenopausal range, and then that low dose moves them up and out of the postmenopausal range. And as the dosing continues, it’s a nice linear trend in the urine and it overlays nicely with the patterns you see in serum.

                                So that’s how I start my frame of mind of the best known products. Then what I want to do with that is overlay, which we’ve done in this paper, the gels and the creams. And the reason that’s really important is because there’s less data on those, but there’s also this huge controversy in our industry because when you put a patch on and you do blood and you do urine and you do saliva, the results look pretty similar. Like, okay, well that makes sense. And then you move to a gel and the saliva values are exponentially higher than what you see in serum and urine. And there were many years when I would’ve told you that because saliva is free hormone, that that must be speaking for the tissue level and so you better lower that dose because there’s a lot of hormone in saliva, therefore there must be a lot everywhere else. And as I’ve interrogated those beliefs that I had, that I had been taught in the industry, what I found is, man, these values are not in alignment with the clinical data on these gel products because they’ve been tested against hot flashes, vaginal atrophy, and a little bit on bone loss.

                                And according to the saliva, we should be using doses that are clinically completely ineffective. And that’s why we really wanted to look at the urine. And when we started the lab, our message was we don’t know. We really weren’t sure what alignment there was between the urine and the clinical. And so this was part of this process years ago before we published this, when we really started digging into the data is what we found is that the lowest dose that’s clinically effective for gels. We know that. Those FDA studies are really nice. They show you what dose works and then they go low enough that you can see it start to fail. And at that point, the values that we see on those low dose products are around the same area as that low dose patch. So minimally clinically effective doses put you in the same range. And I look at that and I think, oh, that makes a lot of sense because when I look at those same products in saliva, the gel is way, way high. Out of the luteal range, really high, giving me the message that, man, I better scale back on that dose. But we know those doses are minimally clinically effective based on placebo controlled studies.

                                So in that, I get a really nice concurrence and affirmation between the lab values themselves and the clinical studies that are done. So we overlay the gel data in this paper and you can see that the data makes a lot of sense, and the patches, they scale up linearly, the gels, they start to tip over, which is exactly the same pattern that we see in serum because the gels are not named after how much do you get in? It’s just how much is on your hand while you’re slathering it all over yourself. And so the low dose is penetrated at a certain level and if you use more volume of that, you don’t get a linear increase. And all of this data makes a lot of sense.

                                So then I can go, okay, now I can look at the big black box, which is the compounded estrogen. We know from the limited studies that have been done that the compounded estrogen creams don’t seem to penetrate as well as the alcohol-based gels and so it takes about twice as much of the cream to drive in as much hormone. That’s what we thought going in. And then when we looked at that data, what you can see is that the creams scale up similarly to the gels, but just at a lower level. So it takes more of the hormone to actually drive in the same amount if the urine is telling us an accurate story. So that’s where my interrogation of that starts is with the patches where everything makes sense and the data is linear and the data makes sense, and then you add on the more confusing of the gels and ask the data, does this make sense based on the clinical studies? And it does. And then we add the cream data in there.

                                And so where it leaves me is thinking that this is a pretty good medium for comparing two women on the same product, whether it’s a patch or a gel or a patch and a gel, just to ask the question, what is our overall estrogen exposure here? And then what we’ve been asking the data is where do those levels correlate with bone mineral density increasing and then the symptomatology relief of hot flashes and vaginal atrophy compared to placebo? Really well-done studies.

                                And so what we’ve been telling people based on that data is if you push people with estrogen and they don’t get out of the post-menopausal range, they’re still down in that post-menopausal range, you’re probably not getting the clinical effect that you want. If you get just out of that range, you’re probably getting mild clinical impact. And as you start to approach the pre-menopausal luteal range, you don’t need to go much higher than the early part of that range. But as you get into that range, that’s where you’re going to see significant clinical impact. And so using the testing to ask the question, how is my estrogen exposure, whether you’re not on therapy or are on therapy, seems to be a pretty strong model for us. The saliva data gives you really, really high data that doesn’t jive with any of the clinical data and the serum data, if you measure a lot of it, it actually makes a lot of sense. But the problem is the up and down pattern is so fast, that’s where serum falls apart, is you’re going to get some low values and think, oh, I need more hormone, but you might’ve just missed the peak because it’s fast. And so the urine, I think is a really nice medium for asking questions related to estrogen therapy. And that’s what we were trying to show in this publication. So sorry, that was a little bit of a long-winded answer.

Dr. Weitz:            No, that’s good. I love this. I’ve got several questions, but the first one is there’s one more form of testing that you haven’t mentioned, which is the pinprick.

Mark:                    Blood spot.

Dr. Weitz:            Yeah. So that’s testing essentially your capillary blood, and there’s some claim that that’s better at picking up these creams.

Mark:                    Yeah. And it’s a very reasonable theory. It just completely falls apart if you actually look at the data. And to be honest, if the clinical data and the blood spot data jived, we would be doing it. Because it’s a beautiful story. It just doesn’t work. And the place that you … And this is really important if people want to interrogate this, well, one, I have reviewed every single study that’s been done on this topic on one particular part on our website. It’s not for those that just want to looky-loo it. It’s pretty deep dive. But here’s the thing. You go to testosterone. Testosterone has tons of data. The pattern is very pronounced, meaning when you put a man on … 25 milligrams is a pretty good place. If you put a man on 25 milligrams, saliva will go sky-high in pretty much every guy. Okay, that tells me something. The capillary blood spot also goes sky-high. Oh, that’s interesting. There’s a correlation there that’s general. If you test people at the same time, the data doesn’t correlate. I’ve done that. But there is this general correlation and this general message that holy crap, that’s a lot of hormone is the general message you get from saliva and blood spot.

                                Okay. What does the serum and the urine say? The serum and the urine are going up modestly. And as you use 50 milligrams, 100 milligrams, they continue to scale up linearly, but on a completely different scale. Remember, if someone’s not on therapy, saliva, blood spot, urine, serum can all correlate fairly well. And then this is the place I start people on this so they understand how little sense this makes. Is if you give those men an injection, the serum, the urine and the saliva all correlate. There’s a very similar pattern. They dance together. There’s one nice study where they did that, and you can see this very parallel pattern. All the people start low, you give them an injection. And in this case it was this long scale, 84 day cycle of an injection or whatever. But at the peak, the saliva was high, the blood was high, the urine is high, so they’re similar. Okay, now stop. Now give them all a gel. You give them all a 25 milligram gel. The saliva and the blood spot go crazy high and the serum and the urine go up moderately. And if you give them 50 milligrams, the serum and the urine will go up again and the saliva and the blood spot will go up again. But again, on a totally different scale.

                                You say, well, perfect. Because testosterone, we have studies at 25 and 50 milligrams, and where we’ve looked at all the things that change with testosterone. Erythrocytosis, muscle mass, LH suppression, sexual function. All this stuff. You can look at the men, then you can shift and you can look at the women. Look at women who use doses that saliva and blood spot say, are you crazy? You should never give a woman this dose. Whereas the blood and the urine are saying, yeah, that’s a reasonable female dose. So we can look at what happened. And then you also have a body of literature on trans men. Super helpful to interrogate this question. Because according to saliva and blood spot, five, 10 milligrams given to a biological female should be incredibly effective at creating the changes you would want to see if someone was transitioning from a female to a trans man. And all of that data dances with the serum and the urine and none of it, not a single study says, you know what? That serum is really underestimating what’s going on in these humans be they male, be they female, none of those studies.

                                Erythrocytosis is the easiest place to see it. I think that makes a lot of sense. If you give a man an injection of testosterone, his erythrocytosis will go up like 60, 70%. Not crazy injections, not I’m a weightlifter body builder, whatever type, just normal injections. Erythrocytosis goes up pretty heavily. Okay, good. Now, if you give a man 50 milligrams of a gel and you pause and you say, okay, let each camp make their prediction, what would you predict? Well, the saliva is saying you’re using 10 times too much hormone. You’re insane. Erythrocytosis is going to go crazy. Whereas the serum and the urine would say that dose of 50 milligrams is clinically effective, but it’s less of an impact than that injection you just gave those other men.

                                And then you look at the erythrocytosis and guess what? It’s significantly less of an increase than the injection. And you go, oh, okay. As it relates to erythrocytosis, serum and urine were telling the truth and for whatever reason, saliva and these blood spot values, which are super interesting intellectually academically fascinating … How is there hormone there that isn’t speaking to erythrocytosis? The problem is when you move to LH suppression, it dances with the serum and the urine. When you move to muscle mass … There’s a great study on muscle mass increase where they took men, they shut down their endogenous testosterone with drugs and then they gave them testosterone back. So they gave them gels. And then they said, okay, split them into two camps. This camp had higher serum than before. This camp had lower serum than before. Now remember, with these doses, everyone’s saliva is super sky-high. Which people had muscle mass increase? Only the men whose serum went up.

                                So you start interrogating these … And this is what I did. I’m working in a saliva lab, I’m doing this, I’m slathering testosterone on myself as a 30-year-old man to try to test this stuff to say, I got to figure out a model where I can start interrogating this, finding data to be consistent with the clinical data. And I just threw my hands up and gave up because you could never make sense of it. And then I did what I should have started off doing is digging into the literature. I’m like, hold on, let’s go see what the literature says about the doses that we use and what happens clinically. And I just walked away going, oh, I expected to find controversy in these studies of, well, these imply serum is right. These studies imply serum is an underestimation and gee, maybe saliva is right, maybe blood spot testing is telling a more true story. But I literally could not find a single study on either estradiol or testosterone where the data implied at all that there was some mysterious way that saliva was telling a true story. So my overall … I wouldn’t say theory. Model that I use, which probably doesn’t describe it exactly, is this. Saliva and capillary blood spot have special access for fat-soluble hormones if they’re applied to the skin. If I filter all of the data through that, it all makes sense to me.

                                Now, I don’t know how it gets from the skin on your foot or the skin on your arm into your saliva gland without getting into the bones and the brain and all of that, but it does. And so that’s where I’m left in that debate and I’m left with testosterone, serum being the gold standard, urine being a nice compliment. And with estrogen therapy because of the pharmacokinetics, I think urine is the best primary way to ask the question, how much did I absorb and then to ask how did I metabolize? So it’s a super complex topic. I’ve dug into it more than anyone I know, and I’ve completely done a 180 on it over about a 15-year period. It’s an interesting topic, and unfortunately there’s a huge section of our educators that really aren’t digging into the literature. They just plant their flag on their position and hold to it. And that’s something that I’m pretty passionate about making people aware of is that if you’re listening to that message, you want to do that and use that model, you can, but you got to know you got no safety net of peer-reviewed literature. It’s all stacked up against that saliva model, which incorporates also the blood spot. So it’s super fascinating. No idea how the blood distributes into those things without getting systemic, but all the data imply that that’s the case.

Dr. Weitz:            One critique I could see someone having of your paper is that you’re comparing a 100% E2 patch to a compounded cream that’s 80% E3 and only 20% E2. So wouldn’t you expect less E2 to show up?

Mark:                    No. We did not take any of the biased data. The paper that we did … So one of the reasons that the cream data is a little jagged and dirty is it’s a smaller subset because we only looked at people on only E2. That’s not bias data.

Dr. Weitz:            Oh, okay. I thought I read that-

Mark:                    There is a serum paper that I cite often because it’s the only … I don’t know how this is true in 2023. There is only one paper that shows compounded estradiol in serum, and that is a bias paper. It’s in a lot of my lectures, so you might be thinking of that one. But that one was … I think it was something like 80/20. And so they followed the estradiol pattern, but those women were also on E3 which no doubt changes things to some degree. We have a whole bunch of bias data too. The problem is it’s really, really dirty data because when women tell us what they’re taking and they tell us when it starts being 80/20, 70/30, 50/50, the confidence with which we know how much estradiol is in one woman’s prescription is just so low that we look at that data, but I don’t think we could ever publish it. So we honed in only on the women that said E2 only was their prescription. So that data is just estradiol.

Dr. Weitz:            I see. Maybe we could touch on one more topic. One of the advantages of doing the dred urine testing is for women whose periods are irregular and maybe they’re trying to figure out what’s going on … Maybe there’s some PCOS symptoms or they’re not sure if they’re in perimenopause or not, is the cycle testing. Being able to measure their hormones every day of the month.

Mark:                    Yeah. So we call it cycle mapping. We have women collect almost every day from day seven until the end, and then if they just don’t have it and it’s longer, they just keep collecting. So what we do is we take the nine most relevant measurements from all of those. So what we’re trying to do is characterize the ovulatory peak and characterize the luteal peak with nine measurements. So that’s what we use that for. It’s a really nice tool for, as you mentioned, people who have wildly irregular cycles or women who … If you’ve had an ablation, which means you don’t bleed anymore, but you still cycle, you have no idea where your luteal phase is. So in cases like that, partial hysterectomies where you don’t have a uterus, but you do have ovaries. Fertility cases where you don’t just want to know, did my progesterone peak, but you want to know, am I maintaining that progesterone. Cases like PMS where maybe you’re fine until the tail end of your cycle and then you feel terrible. So you can interrogate the question of, gee, did my progesterone drop off a cliff? Did my estrogen rise? Did both of those things happen? That type of thing that relates to the timing of the hormones is the purpose of that test.

Dr. Weitz:            Okay. Cool. One more quick question on the paper and then I think we’ll wrap up. Is what we should take from the data about the compounded transdermal estrogen, do we think it’s the way the compounded cream is made, what it’s mixed with why it’s not getting absorbed? Is it that we’re just not prescribing enough of it? Why isn’t compounded estrogen transdermal cream working as well as we thought it was? Do we know?

Mark:                    Well, in terms of absorption, I think you do get less, but this is a general statement made about many products. Some of these women are using a VersaBase, some are using a different base, some are putting it on their forearms, some are putting it on their thighs. It’s a big mix of data. But you can even move out of the compounded world and just go look at Evamist. Evamist is an FDA product. It’s terrible. I’m not saying it doesn’t work, but you have to use four or five, six milligrams to drive in very much. You’ve got just dobs of estrogen everywhere. So I would never suggest that people use that. Now that data is worse than what the compounded creams look like relative to the gel. But there’s a nice paper out of Australia where they looked at serum levels of compound … Not compounded.  There are very few FDA cream products. There is one FDA cream testosterone product in Australia. And so they did a study where they compared … It was probably AndroGel, but I don’t know if it was specifically that product. But a testosterone gel versus their cream product. And what they found is the serum pattern looked exactly the same if you use two X. And this is already a known thing that the alcohol in those gels drives in the hormone such that the absorption is at a higher rate. Now what does that mean? What it means is for the gel, maybe you’re getting 10% absorption and what the cream, maybe you’re getting 5%. Now what you do with that information … You could use it to critique the creams, but it’s not like the gels you’re driving in 50%. So it’s just a matter of what’s the purpose of using a compounded product? For me, those patches are really well standardized, if the pricing and the compliance and all of that is fine, work pretty well, whatever. But when someone needs a compounded product because you want Estriol in there or you want some-

Dr. Weitz:            Well, that’s one of the reasons why is a lot of doctors practitioners feel that you’re lowering breast cancer risk by giving the Estriol as part of it.

Mark:                    Yeah. And you’re talking to a chemist here so I am not an expert in that, but my team’s been researching that pretty heavily, our clinical team. And it may be true, but I don’t believe that’s a proven … That’s a theoretical concept that we’ve run with that I think our industry would be wise to put some effort into in terms of evidence, in terms of whether that actually plays out in real life or not.

Dr. Weitz:            I think that’s come from just a concept that Estriol is a weaker estrogen.

Mark:                    Right. Right. So then is it better to use a lower dose of Estriol and leave it alone or is it better to Estriol? I honestly do not know. But if your conviction is that you need some Estriol in there, absolutely use a compounded product. And you can know that from one compounder to the other for how your patient puts it on, where they put it on the absorption is going to be different. Now that doesn’t mean it’s a bad thing. What it means is it’s a little bit of a black box for you. And that’s where I think the testing comes in helpful. But where it just so happens because of this paradox with saliva testing that the tool that you grab to ask the question, how’s my estrogen dose profoundly changes your dosing?  I know so many people when I was in the saliva world that would use .05 and you think oh .05 cream. Hey, a .05 patch is pretty big. And guess what? When you use a .05 cream, you can get higher numbers in saliva than a .05 patch. But then you pause and you step back from that and go, wait a minute, the .05 patch has like five milligrams of estrogen in it, and I know I’m delivering .05. The .05 cream means on your skin is .05 and then how much gets absorbed? Well, the question to that depends on which test you use. If you use saliva, what it’s implying is it’s all absorbed. That this barrier called your skin allows all that hormone through. And maybe that was going to be true, but as the clinical data has come out … And we can look at all the studies, it’s not true. When you look at a gel of .25 and .5, it appears that maybe 10% of it gets through. And the truer lab value that is aligning with the clinical data on that, I think is the urine.

                                And so I think using a product that drives a urine level up into that range where either a .025 or a .05 patch sends the average woman is the place at which we can be, I think more assured that estrogen’s efficiency is being achieved. And so if you’re using a compounded product, I think that is the way to go in terms of asking yourself, how much did I actually deliver? Because again, the blood test is going to change too fast. The saliva test is going to give you a big number that so far as I can tell, has zero clinical relevancy. And I know that that will step on some toes, but you can’t point to a single study that leans in that direction. They all lean in the other direction. So if people want to go in that direction, they can. We are not going to be offering that testing for that very reason that we just can’t substantiate the worthiness of those values in those situations. And the urine seems to be doing well in terms of telling a story that’s in alignment with the clinical data.

Dr. Weitz:            I noticed when you mentioned the amount to achieve better bone health, you didn’t mention anything about cardiovascular health. Do we think that’s a similar amount or are we more confused about the cardiovascular picture these days? Do we still think that estrogen has serious cardiovascular risk reduction?

Mark:                   We as a pronoun, that involves many of us, including me, but I am not an authority on that topic at all. So I would have to defer to people like Dr. Doreen Saltiel, and people that are experts in both the cardiovascular and the HRT side of it.

Dr. Weitz:            I thought they went hand in hand.

Mark:                   I think it’s a little bit more less clear in the literature, and I believe there is some justification for moving up just a little bit higher. So in serum instead of that 40 to 60 to range to maybe more that 60 to 80 range. But I am by no means an expert in that except to say that there are cardiovascular benefits of HRT, but where those target values are specifically for cardiovascular disease, I would not want to speak to specifically because I wouldn’t consider myself an expert on that side of it, even mildly.

Dr. Weitz:            Sounds good. So how can viewers and listeners … Practitioners find out more about the Dutch test, and I guess patients, lay persons who are listening to this find a functional medicine practitioner who’s offering the Dutch test?

Mark:                   Yeah. I think for patients, if you go to dutchtest.com, you’ve got to find a provider function. We always try to push people in that direction because this is complex stuff. Trying to walk this path on your own without a really good healthcare provider I think is very, very difficult. For providers at dutchtest.com you can sign up to become a provider, and we’ve got all kinds of educational resources. We just launched a mastering functional hormones course, which can be a really good way to just dip your toe in a little bit at a time, but then emerge from it competent at this whole hormone game. It’s just like hormones 101 and Dutch 101. And that’s would be my encouragement to a provider, is to try the test as a provider, but also go through our education there is really helpful.

                                And our team is … We’ve got 10, 12 doctors on staff who use this in their practice and are ready to help people get over that bridge of comfortability with the test. Because the Dutch test offers a lot, and that’s a two-edged sword in that it takes a little bit of time to get up to speed with what do I do with cortisol metabolites? What do I do with the androgen metabolites? How do I tie it all together? What some of these organic acids that you’re including and how does it change my treatment protocol? So we are really focused on education and helping people really leverage the testing as much as it can be. And again, for patients, go find a provider that is really gifted at functional medicine that can help you with your own health journey. If patients want to order the test on our website, they can, but we really do encourage people to order through a provider and to go that direction because I think that’s a … You’re going to get better outcomes I think, when you have an expert to walk your path with you.

Dr. Weitz:            Great. Thank you so much, Mark. Great information.

Mark:                   All right. Thanks Ben. Appreciate the time.

 


 

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