What Really Causes Autoimmune Disease with Dr. Todd LePine

Mark Hyman, MD

Full Transcript

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Dr. Todd LePine(00:00): When you go into the medical literature in autoimmunity related to lupus, the Epstein-Barr virus is associated with seven different autoimmune conditions, multiple sclerosis, rheumatoid arthritis, lupus, type 1 diabetes, ulcerative colitis. Dr. Mark Hyman(00:14): Welcome to The Doctor's Farmacy, I'm Dr. Mark Hyman and that's Farmacy with an F, F-A-R-M-A-C-Y. A place for conversations that matter and if you suffer from autoimmune disease, if you have lupus, this conversation is going to matter to you, or if you know anybody who's got these problems because they affect 80 million Americans one type or another, which is more people than have heart disease, cancer, and diabetes combined. So it's a big problem and has poor answers with traditional medicine. Dr. Mark Hyman(00:44): We have today with us my colleague at the UltraWellness Center, Dr. Todd LePine who's an incredible physician. He's one of the leaders in functional medicine, teaches all over the world. He graduated from Dartmouth Medical School, he's been working with me for I don't know, God now 25 years together we've been on this road? Dr. Todd LePine(00:59): A long time. Dr. Mark Hyman(00:59): He looks the same as the day I met him, I don't know he does it. He doesn't have one gray hair on his head and he's going to talk to us today about a patient of his with lupus who had autoimmune disease that is a very common problem with very bad outcomes. It can lead to brain issues, kidney failure, lung issues, joint issues, it's a really horrible problem. So Todd tell us, what is lupus and what is the traditional approach in medicine to this problem? Dr. Todd LePine(01:30): All right so lupus actually comes from the Latin word meaning wolf and typically people with classic lupus will get a facial rash, it's called a malar rash. It's like a butterfly rash and over time they say that you develop a wolf-like appearance. Dr. Mark Hyman(01:49): Yeah their cheeks get all red and their eyes- Dr. Todd LePine(01:52): Yeah, exactly and that's due to photosensitivity. So lupus is one of those conditions which we see a lot, interestingly it's about nine times more prevalent in women. So that raises the question, well what's the difference between women and men and why are women getting- Dr. Mark Hyman(02:08): I'm still trying to figure that out. Dr. Todd LePine(02:11): I actually think I have a insight into that, it's really quite interesting. Dr. Mark Hyman(02:16): How men and women are different? Dr. Todd LePine(02:16): Yeah, how men and women are different, right right. Then the other thing that is also interesting is that we traditionally treat it with medications like steroids, Methotrexate, Plaquenil, those kinds of things which all have significant side effects and in my opinion, one of the- Dr. Mark Hyman(02:38): These are powerful immune-suppressing drugs, right? Dr. Todd LePine(02:40): Oh yeah. Dr. Mark Hyman(02:40): And they even use biological agents, which- Dr. Todd LePine(02:42): Biologics. Dr. Mark Hyman(02:42): Which really shut off your immune system and they can work but they're often fraught with danger including the risk of cancer and overwhelming infection if you get a bad infection so they're not... they're very expensive, up to 50 grand a year per person. Dr. Todd LePine(02:58): Yeah, yeah. Also, one of the things that was intriguing to me when I was doing my training was drug-induced lupus because we were taught that lupus is an autoimmune condition but there is a condition called drug-induced lupus and that always raised my question, well how is a drug causing lupus? What we see is that, I think one of the major drugs was an older drug called Procainamide, I don't know if you remember using that but it was an antiarrhythmic and in certain patients who got Procainamide, they would develop lupus. Looks just like what we call lupus SLE, systemic lupus erythematosus. Dr. Todd LePine(03:35): That always fascinated me that a drug would be triggering this and when I actually went down that sort of rabbit hole, what we find out is that Procainamide can actually damage DNA and it's probably theorized that some types of things, like drugs or stealth infections like viruses may trigger the body and cause some damage in the DNA and when we test for lupus, some of the tests that are are double stranded DNA antibodies. Dr. Mark Hyman(04:05): The traditional blood tests look at what are the autoimmune antibodies that- Dr. Todd LePine(04:09): Yeah, and it's interesting because there's a whole bunch of different markers that are used in the diagnosis of autoimmune conditions. You have autoimmune panels, like the traditional one is ANA, antinuclear antigen, traditionally in patients who have lupus that's positive and then you can look for other biomarkers like double stranded DNA and such. Dr. Mark Hyman(04:28): And ANA can be positive in many, many people even if they don't have lupus and there's this whole phenomenon of pre-autoimmune disease where you're starting to have these autoimmune antibodies but you don't really have a lot of symptoms yet but your body- Dr. Todd LePine(04:38): Right, and that's- Dr. Mark Hyman(04:38): It's like pre-diabetes, like pre-autoimmune disease. Dr. Todd LePine(04:40): Exactly and I always tell my patients that's like when the check engine light comes in your car. Dr. Mark Hyman(04:44): Exactly. Dr. Todd LePine(04:45): If you ignore that, you're going to get smoke coming out of the hood soon. Dr. Mark Hyman(04:49): Which traditional medicine ignores, right? Dr. Todd LePine(04:50): It totally ignores. Dr. Mark Hyman(04:50): If you don't meet these five criteria for this diagnosis then you don't have it and we can't treat you. Dr. Todd LePine(04:55): Right. Dr. Mark Hyman(04:56): It's like the patient I had who came with a blood sugar of 120. I said, "Geez, has your doctor checked that out?" He's like, "Oh yeah." I said, "What's happening, what did he recommend." He says, "Well, he said I should watch it until it's 126 and then he'll give me treatment for diabetes." Dr. Todd LePine(05:09): Isn't that crazy? Yeah. We'll wait until the horse is out of the barn and then we'll try to corral it. Dr. Mark Hyman(05:14): Yeah. Dr. Todd LePine(05:15): Yeah, it's unfortunate but when you look at how many people do have conditions that are... you know, even subclinical hypothyroidism, there's a lot of things that if you look early enough, it's a lot easier to treat them when you catch them early. If you're starting to have early cognitive decline, Alzheimer's is a lot easier to treat when you catch it early. Diabetes is a lot easier, heart disease, autoimmune conditions. So preemptive, personalized medicine is the way to go. Dr. Mark Hyman(05:46): That's what we do at the UltraWellness Center here, functional medicine. Dr. Todd LePine(05:48): Yeah. Dr. Mark Hyman(05:49): So this patient had this condition that was treated by traditional medicine, was she on a bunch of drugs? Dr. Todd LePine(05:54): She actually came in, had done courses of primarily Plaquenil and Prednisone and she was actually pretty proactive in her self care, if I remember right- Dr. Mark Hyman(06:09): And Plaquenil by the way, for those listening, is the same as Hydroxychloroquine that they're using for COVID-19. Dr. Todd LePine(06:13): Right, and we also realize that Plaquenil is actually an antimicrobial, it's used for Malaria, that's the original use for it. Somebody must have had Malaria and then developed lupus and they said hey, this is working. That's sort of how they sort of discover other uses for medications. Dr. Todd LePine(06:34): This particular... she was actually involved in the healthcare field. I think she was a therapist if I recall properly and so she had done a lot of stuff on her own. The big thing with her is that, and she told me this, that she felt that her lupus was actually triggered by stress. She had a son who had some medical issues and was having issues both with dealing with a teenager who was having some illness and that sort of tripped it over. Oftentimes, if I take the history of patients who develop an autoimmune condition, it's oftentimes followed by a period of chronic stress that's unrelenting. It's a very, very common thing and- Dr. Mark Hyman(07:16): Well let's talk about stress for a minute because my thinking about stress is it sort of sets the table for other things to sort of take over. Dr. Todd LePine(07:24): Yeah. Dr. Mark Hyman(07:24): So- Dr. Todd LePine(07:25): It doesn't cause things. Dr. Mark Hyman(07:26): Not in and of itself, it may cause some illnesses for some people but for the most part it exacerbate whatever is going on. So if you're stressed, your immune system is suppressed, you're going to get more inflammation and then if you have underlying issues like this woman is, they're going to come out. Dr. Todd LePine(07:40): Absolutely. Dr. Mark Hyman(07:41): So tell us how you approach this from a functional medical perspective. How do we think about autoimmune disease in general from a functional medical perspective and lupus particularly? Dr. Todd LePine(07:50): When I see a patient who has lupus and I go down sort of the checklist, so I look at okay, do they have sensitivity to gluten? The other thing I find in a lot of lupus patients is Epstein-Barr virus. So Epstein-Barr virus is the virus that causes mono and mono stands for mononucleosis because the virus infects your white blood cells and the thing about Epstein-Barr virus is it's very common, about 70-80% of the population has it and most of the time the immune system will clear it. It's a herpes class virus, just like a cold sore and once you get a herpes cold sore, the virus stays in your body all the time. Most of the time the immune system keeps it in check but there are certain individuals where the virus while reactivate and the herpes virus will come out or the mono can actually reactivate. Dr. Mark Hyman(08:39): So a cold sore on your lips is basically a herpes virus. Dr. Todd LePine(08:42): Herpes virus. Dr. Mark Hyman(08:43): And it doesn't come out all the time, it comes out under stress. Dr. Todd LePine(08:46): Under stress- Dr. Mark Hyman(08:47): Cold weather. Dr. Todd LePine(08:48): Exactly. Dr. Mark Hyman(08:48): Emotional stress- Dr. Todd LePine(08:49): Too much sunlight. Dr. Mark Hyman(08:50): Getting a cold, sunlight. So it's sort of a latent virus, we all live with hundreds of viruses in us, when we're stressed it allows those viruses to emerge, right? Dr. Todd LePine(09:00): Exactly. Dr. Mark Hyman(09:03): So this is what happened with this patient it sounds like. Dr. Todd LePine(09:04): Yeah. I always like to go down and ask the question so why is this, why do women have lupus more than men? Dr. Mark Hyman(09:12): Well that's functional medicine is why, why, why as opposed to what. Dr. Todd LePine(09:15): Right, and interestingly when you go into the medical literature in autoimmunity related to lupus, the Epstein-Barr virus is associated with seven different autoimmune conditions, multiple sclerosis, rheumatoid arthritis, lupus, type 1 diabetes, ulcerative colitis. So what happens is the virus, in some cases patients will reactivate and it causes the stimulation of the immune system and the immune system will then start reacting to it and then interestingly, I've always been curious about photosensitivity. Why does photosensitivity happen in patients who have lupus? What's going on there? Why is it when they get sunlight is it affecting them and what I found out in the literature is that the virus causes the body to produce more interferon gamma and interferon gamma is one of the cytokines that help our bodies to fight off viruses and when we have high levels of this interferon gamma, it sensitizes the body to sunlight so that's why you get that sort of lupus-like photosensitivity, especially with exposure to sunlight. Dr. Mark Hyman(10:26): And interferon is one of the treatments they're looking at for fighting COVID-19. Dr. Todd LePine(10:29): Yes. So what they do is they have an overabundance and it may be a genetic predisposition, there may be some single-nucleotide polymorphisms that certain lupus patients have and they produce lots of interferon gamma and that actually gets involved in the skin cells and it can make them more photosensitive so it's an interesting phenomenon. The other thing and I've seen this with a lot of regular mainstream doctors, they'll say well you can't really check for Epstein-Barr virus because if the antibodies are positive it just means that you've been exposed to it. Well that's true, but if you actually do specific testing for Epstein-Barr virus, so there's a panel that we do which checks for antibodies to the nuclear antigen and cytoplasmic antigen and then also the early antigen and then I'll also throw in the Epstein-Barr virus by PCR. So PCR is checking for the DNA of the virus. Dr. Mark Hyman(11:24): So you're actually seeing if there's live virus rounds circulating in your blood, not just your immune response to it? Dr. Todd LePine(11:29): Exactly. Typically in the panel that we use, if you have three out of four antibodies that are positive especially with the early antigen and or with the PCR or the Epstein-Barr virus you know proof positive that the Epstein virus is- Dr. Mark Hyman(11:43): Reactive. Dr. Todd LePine(11:44): Reactive, exactly. Reactive. That's where then you have to ask yourself, well what do I do to calm down that particular virus so there's a lot of things that you have to look at, it's- Dr. Mark Hyman(11:58): Yeah, true functional medicine really has a different perspective and it's why we see so many patients here at the UltraWellness Center who've tried so many things and then they get better because we look at all the factors. So when I think of an autoimmune patient or just any disease in general, there are really only five main triggers. It's a toxin, so I've had patients with lupus who have autoimmune disease triggered by heavy metals, for example. Could be- Dr. Todd LePine(12:20): Mercury. Dr. Mark Hyman(12:21): An infection like lupus or it could be the microbiome changes. Dr. Todd LePine(12:25): Yes- Dr. Mark Hyman(12:25): An allergen, something they're eating like gluten and it could be poor diet which is inflammatory and has for example, a lot of the emulsifiers in our food like carrageenan and all these gums. Dr. Todd LePine(12:37): Yes. Dr. Mark Hyman(12:38): They cause leaky gut driving inflammation and it also can be stress, like you said, and oftentimes it's many of those things together. Dr. Todd LePine(12:45): Exactly, yes. Dr. Mark Hyman(12:46): So for her, it was a few of those things. For her it was stress and the virus and also her gut was a mess too. Dr. Todd LePine(12:52): Yes, her gut was a mess. Yeah. So the other things that she noticed is that if she ate foods that were high in lectins, things like the nightshade family, that her symptoms actually got worse and it was interesting, some of the work by Peter D'Adamo. who is the author of the Blood Type Diet, he's the guru of lectins. What we find is that in certain individuals, when you have high lectins in your diet and these are compounds that are found in plants which actually act as a defense mechanism for the plant so that animals and insects are less likely to eat them. Lectins, there's a... in the medical literature, a case study of a hospital that thought they would have a healthy eating day so they served everybody red kidney beans in some type of a casserole or a soup and then everybody got sick from it because it was very high in lectins and it actually caused transient leaky gut. They had an immune response to the lectins in the plants and I've had a number of patients because not everybody will have that response to lectins. Dr. Mark Hyman(13:51): Yeah, I mean there's a lot of promotion out there of lectin-free diets as the cure for everything. Dr. Todd LePine(13:56): Or low lectins, low lectins. Dr. Mark Hyman(13:58): Yeah. Dr. Todd LePine(13:58): It's impossible to get- Dr. Mark Hyman(13:59): A low lectin diet and I think it can be helpful for some specific patients. I think that the thing is that everybody finds the latest fad and think it's the cure for everything, it's really not and when you're in functional medicine you get humbled by understanding how complex things are, how everybody's really different, how one person may tolerate gluten and another person may not. One person may be fine with lectins and another person may not but if you have an autoimmune inflammatory condition, it's something worth trying. Dr. Todd LePine(14:24): Absolutely. It is and I'll interject here because this is an interesting finding. I stumbled upon this and again this was actually by Peter D'Adamo who got me down this rabbit hole because I just recently had a patient who had five autoimmune conditions including lupus and I checked for a lab test called mannose-binding lectin. Have you ever checked for it? Dr. Mark Hyman(14:47): Actually no, but I know about it. Dr. Todd LePine(14:49): Right, it's one of those things and he's the one who got me to understand this. So mannose-binding lectin is a compound that our body makes to bind mannose and a lot of- Dr. Mark Hyman(15:00): That's a sugar. Dr. Todd LePine(15:01): It's a sugar, mannose is a sugar and what you find out is that people who have mannose-binding lectin deficiency are at a higher risk for lupus and hers was undetected. Dr. Mark Hyman(15:12): Yeah and I think the other thing I want to just point out is that you know, you're talking about this patient with lupus and she had gluten and she had gut issues, she had stress, she had this virus, she had a lectin sensitivity, but that was her. If you take 10 other patients with lupus- Dr. Todd LePine(15:23): They're all different. Dr. Mark Hyman(15:24): They're all different. Dr. Mark Hyman(15:25): Hey everybody, this is Dr. Hyman. Thanks for tuning in to The Doctor's Farmacy, I hope you're loving this podcast. It's one of my favorite things to do an introduce you to all the experts that I know and I love and that I've learned so much from and I want to tell you about something else I'm doing which is called Mark's Picks. It's my weekly newsletter and in it I share my favorite stuff from food to supplements to gadgets to tools to enhance your health. It's all the cool stuff that I use and that my team uses to optimize and enhance our health and I'd love you to sign up for the weekly newsletter, I'll only send it to you once a week on Fridays, nothing else I promise, and all you have to do is go to longevityfilm.com/picks to sign up. That's longevityfilm.com/picks, P-I-C-K-S, and sign up for the newsletter and I'll share with you my favorite stuff that I use to enhance my health and get healthier and better and live younger, longer. Now back to this week's episode. Dr. Mark Hyman(16:20): And the problem with traditional thinking is that everybody with lupus gets the same treatment. Once you make the diagnosis, you stop thinking and in functional medicine, when you have the diagnosis, that's when you start thinking. It's just the first step of solving the problem, it's like okay, this is what your picture looks like, okay what are the potential factors that we need to think about to get to the root cause and then we have to treat the cause not the symptom. Dr. Todd LePine(16:44): Yes. Dr. Mark Hyman(16:45): That's the beauty of functional medicine. So for her, how did you treat the causes of her lupus and what happened? Dr. Todd LePine(16:51): Well for her it was really focusing on... she already actually was doing very well, I actually tested her... even though she said that she was eating a clean diet, I made sure. So she said she was avoiding gluten, avoiding dairy, avoiding dairy and her testing was negative for any reactions to gluten so I said, "You're doing a good job, keep it up." It was negative for leaky gut, you're doing a great job. Let's do that. But what I did do, and she had never had done, is she did tell me that she had a bad case of mono when she was a teenager and my theory with her is that she probably went under this very stressful time period that this Epstein-Barr virus reactivated for whatever reason and hers was, she had a positive PCR, so the DNA of the virus was floating around in her blood and also she had positive antibodies. Three out of four of her antibodies were positive. That was to me, a smoking gun that her Epstein-Barr virus was really driving her lupus symptoms. Dr. Todd LePine(17:46): So initially what I did is I treated her with some medicinal mushrooms, things like turkey tail. I used also lysine which is an amino acid which can help and I combined that also with some Monolaurin. Dr. Mark Hyman(17:58): Yeah lysine is often something people will take to prevent herpes outbreaks on their lip. Dr. Todd LePine(18:02): It works well. Dr. Mark Hyman(18:03): It works incredibly well. Dr. Todd LePine(18:04): It works quite well. Dr. Mark Hyman(18:04): Because that helps inactivate the virus and other foods that contain arginine like nuts, which are good for you, but in this case they have high arginine levels that actually can activate the herpes virus. Dr. Todd LePine(18:16): Yes and that's an interesting observation. So that was one of the ways in which I initially treated her and she did get some improvement with that and then another thing which I added to her regimen is low-dose Naltrexone. I'm sure you use that yourself and I've been really amazed at- Dr. Mark Hyman(18:36): What is Naltrexone? Dr. Todd LePine(18:38): So Naltrexone, this is in an interesting thing. So Naltrexone is an opiate blocker and I'm not sure how they actually stumbled upon this but if somebody takes too much opiates and they overdose, you can give Naltrexone to block the effect of the opiate overdose- Dr. Mark Hyman(18:54): And when someone has an overdose of heroin or narcotic they give them NARCAN which is Naltrexone and that stops them from dying. Dr. Todd LePine(19:01): Exactly and it's theorized that when you give Naltrexone at very low doses, what you do is you block the body's own opioid receptors and the body senses that and it starts producing more natural feel good molecules, endorphins. These are our own body's pharmacy for the pain molecules which in turn modulates the immune system. So when you up-regulate opioids, you're actually modulating the immune system and I used to use it primarily in patients with ulcerative colitis and multiple sclerosis but now I'm using it in a lot more patients and I find that it works really quite well in a whole host of autoimmune conditions. So I used it in her- Dr. Mark Hyman(19:45): And it's very low toxic effects. Dr. Todd LePine(19:47): It's probably the safest thing, it's- Dr. Mark Hyman(19:49): Yeah, very safe to use. Dr. Todd LePine(19:50): Yeah, you can have a couple of side effects in a few people but it's probably one of the safest medications that I prescribe. Absolutely. It has to be compounded and you slowly work your way up on it. Dr. Mark Hyman(20:01): My experience with it is that it can help but unless you deal with the root cause, again it's a symptom manager. So it can help mitigate the symptoms but it's not going to address the underlying biology. Dr. Todd LePine(20:10): Exactly, you're actually true. It's not going to reverse the condition but it's one of those things where the risk-benefit is so good that it's worth doing in a lot of patients. So I actually added that to her and then we went to the next level which is we tried the natural route and then she got some benefit but it wasn't really where she wanted to so I said well let's go ahead and we'll give her an antiviral, so I actually gave her some Valtrex at high dose. I gave it to her I think three times a day, I think you probably have done that yourself, high dose Valtrex for Epstein-Barr virus. There is no simple, one size fits all treatment for Epstein-Barr virus, I've learned that. There really isn't and she actually responded remarkably well to that. Within a couple of months she was like 80% better using the Valtrex and I've had a few patients that that was very, very- Dr. Mark Hyman(21:00): Yeah, I think that's right and I think what's interesting, the more you do this the more you realize what works with one person may not work with another person. Another person who had Epstein-Barr, you give them Valtrex it may not do anything and I think I've had the same experience, some patients you give them this relatively benign antiviral like Valtrex and it works well, others don't respond to that. I've had other patients who use something called Valcyte which is very expensive and has higher levels of toxicity but it actually can be effective in select patients. I think there's other therapies that she used which are also important to mention because as I've gotten more experience in this, I'm more interested in how do I activate the body's own healing systems? How do I use therapies that are regenerative? How do I use therapies that are facilitating the body's own ability to fight things and she ended up using one of these therapies, so can you talk about that? Dr. Todd LePine(21:51): Sure. Yeah, well before I actually talk about that, the other thing that also I've used in patients is intravenous Vitamin C and that's actually in the medical literature. High v Vitamin C at a fairly high dose is about 25-50 grams has been shown to be very effective also for Epstein-Barr virus, so that's another thing. In her particular case- Dr. Mark Hyman(22:10): And by the way, how does that work? Dr. Todd LePine(22:11): How does that work? Well at high levels it actually works as a pro-oxidant. Dr. Mark Hyman(22:17): So we think of Vitamin C as an antioxidant but actually it's working as a pro-oxidant, so- Dr. Todd LePine(22:22): Which goes into the next therapy which is the therapy that- Dr. Mark Hyman(22:24): And how do they do that? Do you want to explain how- Dr. Todd LePine(22:27): Well it's a Ying and a Yang because there's reduction, which is the adding of electrons and oxidation which is the removing of electrons and it has to do with a coupling, coupling of the oxidative forces versus the reductive forces so it's a little bit like a magnetic pull. Dr. Mark Hyman(22:43): And at high doses, Vitamin C increases the release of hydrogen peroxide from the white blood cells. So people don't understand this but how does our white blood cell kill bugs? Dr. Todd LePine(22:56): We bleach them. Dr. Mark Hyman(22:56): It produces bleach, hydrogen peroxide, and ozone which are all oxidants, right? Dr. Todd LePine(23:02): Yes. Dr. Mark Hyman(23:02): So that's exactly how our bodies kill things and it sometimes can't do the job and using these other therapies like high dose Vitamin C can help actually increase the body's ability to kill infections and they have actually studied it in ICUs, they're using it in COVID-19. Dr. Todd LePine(23:17): Yeah you bring up a really interesting point which is that these... and actually there's a term in medicine called redox signaling molecules and when you have these redox signaling molecules, which ozone will be one, it actually up-regulates your body's own reparative forces. Dr. Mark Hyman(23:33): So talk about what she did with ozone. Dr. Todd LePine(23:35): Yeah, ozone was a game changer for her. She ended up using ozone and she said it was like a game changer for her because it was the first time I had a patient who had lupus who responded to ozone in that way and it was really quite amazing. Dr. Mark Hyman(23:50): So how did she get the ozone? Dr. Todd LePine(23:55): Actually it was administered by a local physician who she was seeing, because she was seeing me in consultation and she actually got it rectally and intra-vaginally- Dr. Mark Hyman(24:05): So not even intravenously. Dr. Todd LePine(24:06): She didn't even get it intravenously and she had that response, it was really quite- Dr. Mark Hyman(24:09): You can give it intravenously, you can give it in the muscle, you can give it rectally, vaginally, it's absorbed and it can be very, very effective. Rectal and vaginal treatments you can do at home and you don't even need a doctor to order it. Dr. Todd LePine(24:19): Yeah, I mean it's basically oxygen on steroids is really what it is. Dr. Mark Hyman(24:23): Yeah, high dose oxygen with a little bit of ozone. Dr. Todd LePine(24:25): Right, so go out after a thunderstorm and you get that nice clean smell afterwards, that's ozone in the air. That's the lightning producing ozone. It's a special reactive species of oxygen. Dr. Mark Hyman(24:38): And it's one of those oxidative therapies, just like Vitamin C that gives you a little bit of stress but it also activates your body's own anti-inflammatory mechanisms, antioxidant mechanisms. Dr. Todd LePine(24:48): Absolutely. Dr. Mark Hyman(24:49): Yeah. It can be antiviral and kill bugs which is powerful. So I think it sounds like a wacky therapy but it's something we do here at the UltraWellness Center. Dr. Todd LePine(24:58): Yeah, I mean- Dr. Mark Hyman(25:00): I know we were talking about earlier, when we both heard our patients talking about this, and I often heard this, "Dr. Hyman, I tried everything and I did ozone therapy and it was the thing that made me better." And I was like oh that's interesting and I had a little footnote in my head but I was like it's a little weird, I don't know about that and when I got sick with mold toxicity and autoimmune and colitis, it was the thing that actually flipped my body into a healing response and it doesn't treat any disease, it just activates your body's own healing mechanisms- Dr. Todd LePine(25:30): Very powerful. Dr. Mark Hyman(25:30): Very powerfully and very quickly. I had autoimmune disease, brain fog, and within a few days... it wasn't like it took weeks, it was in a few days I really turned around dramatically. Dr. Todd LePine(25:42): Absolutely, yeah. The other thing which I'll mention as it relates to lupus in women and I've found this and actually, again whenever I see something that's sort of out of the box thinking I'll go into the medical literature and see if it's substantiated and what I found is a pattern in patients who have lupus is their estrogen detoxification pathway and when we check estrogen levels and hormone levels in patients, we don't just check your estrogen and maybe your progesterone, we check all of the hormones and then we also check the metabolites of the hormones and I've found this pattern in not all lupus patients, but some lupus patients is they have a increased pathway for metabolism to what's called the 4-Hydroxy estrogen. 4-Hydroxy estrogen is not... you're not going to go to your regular doctor or your OBGYN- Dr. Mark Hyman(26:32): They're not going to check that. It comes out in the urine. Dr. Todd LePine(26:34): It comes out in the urine, exactly. It comes out in the urine and I learned about this through Jeffrey Bland- Dr. Mark Hyman(26:38): And it's one of the things we test here at the UltraWellness Center. Dr. Todd LePine(26:40): Exactly, and Jeffrey Bland, he basically called this the dancing Shiva and in some individuals, because a woman's hormones go up and down and they have to be detoxified throughout the monthly cycle and you oftentimes will see patients who have lupus, they'll flare with their cycles and when you measure their 4-Hydroxy estrogen, they're very high and the 4-Hydroxy estrogen is what's called a quinone adduct. So it damages DNA and when you have high levels of this over time, it actually increases your risk for breast cancer. Dr. Mark Hyman(27:12): This is why you think women might have a higher risk of lupus? Dr. Todd LePine(27:15): Absolutely. Absolutely. I actually have a literature paper that cites this and I've been doing it in my own little cohorts of patients and I oftentimes check it and in a lot of patients they have that and then the other thing that's interesting- Dr. Mark Hyman(27:27): So wait, wait. Before you go, I just want to unpack that because that was very powerful what you just said. What you said is that there are some women who have trouble metabolizing estrogen and it goes down a pathway that produces a toxic estrogen that damages DNA which is what we see in lupus and that by fixing that, and we know how to fix that with functional medicine using food and various nutrients and herbs that actually have up-regulator fix those pathways, these patients can get better. Dr. Todd LePine(27:52): Absolutely. Yes, absolutely. The other thing- Dr. Mark Hyman(27:55): So by the way, most traditional doctors would not be looking at your hormones if you have lupus. Dr. Todd LePine(27:59): Right, and then the other thing that we then do is we then look at the genetics. So we look at your genetic pathways, so there's a specific polymorphism called the 1B1 pathway and when that has a variation, you are more prone towards producing the 4-Hydroxy estrogen so typically you start looking- Dr. Mark Hyman(28:15): How would you fix that? Dr. Todd LePine(28:17): Well what you do, and interestingly the particular snip that's involved in that particular pathway, that gets actually up-regulated by polycyclic aromatic hydrocarbons, basically if you eat a lot of charcoal broiled food and barbecue, you're going to be up-regulating that pathway. So if a patient's got lupus, you don't want them eating- Dr. Mark Hyman(28:37): Whether you're grilling your vegetables or grilling your steak it's going to cause the same problem. Dr. Todd LePine(28:39): Exactly, it's the ash. It's those complex- Dr. Mark Hyman(28:44): Blackened stuff. Dr. Todd LePine(28:44): Blackened stuff. Exactly. That up-regulates that enzyme. The other thing which you can do is by adding through your diet cruciferous vegetables, supplements like DIM, helps to shift that pathway in a different direction so it's very, very powerful stuff and when you start doing the testing and start looking at it from all different angles, you can really move the needle. Dr. Todd LePine(29:05): I'll never forget this one patient where I first learned about this, the patient basically told me in her history that everything started after she got mono as a teenager and her life changed after that and she was never able to clear it. When I checked her estrogen and estrogen detox pathway, she had the highest 4-Hydroxy I'd ever seen. She was very, very sick. That's where I sort of understood okay, this may be playing a role with the sex differentiation between men and women in lupus because it's like nine times more prevalent in women. Dr. Mark Hyman(29:37): Yeah, so this is such a great example on a case of someone who has an autoimmune disease which is so common that you acted like a medical detective and you found all the various things that were going on with her. She had sort of this chronic Epstein-Barr infection that was reactivated by stress, she had gut disturbances, she had lectin intolerance, she had gluten sensitivity, she had this hormonal dysfunction with abnormal estrogen metabolism and these are the kinds of things that we do here at UltraWellness Center to help us navigate to how to treat each person as an individual. This is really personalized medicine, personalized nutrition and it's very sophisticated, its very effective and it's something that helps relieve suffering for so many people when they get stuck and I feel like this is where we're going in medicine, it's where the science is going. Dr. Mark Hyman(30:32): Functional medicine is just an approach that helps us apply the science of systems medicine and network medicine today, rather than waiting 10, 20, 30 years, we actually know how and we're learning every day. I mean when I think about how little we knew about the microbiome when we started this 25 years ago and how much we know now, we were literally groping in the dark but we had the basic idea and we were able to apply this principles and get people better even if we didn't quite understand what was happening, right? Dr. Todd LePine(31:03): Exactly, yeah, yeah. Dr. Mark Hyman(31:03): It was quite amazing. So I mean I think it's important for people to understand that this is one case of lupus and this was her issue but these are common themes and for somebody else with lupus it might be something else and this is really the beauty of functional medicine, it's why we have such great success here, we have providers, a collection of doctors and staff here who have been working on this for 60 years collectively treating these complex patients from all over the world, we're now doing virtual consultations given COVID-19 we've now switched over because now we have the ability to do that and I just encourage anybody who's struggling to think about getting help and they're welcome to come see us at the UltraWellness Center, they can go to UltraWellnessCenter.com and we're here to help you and navigate through some of these complex issues and figure out what it is that is your issue that needs to get treated. Dr. Mark Hyman(31:49): I think that's so encouraging to me because I love doing this because I remember working as a traditional doctor and I was good at prescribing pills and matching the pill to the ill and people would manage their symptoms but I got sick of managing and I wanted to fix things and that's the beauty of functional medicine, is that we help relieve needless suffering for millions of people all over the world from practitioners in every country and this is the future where it's going, we're just a little ahead of the game. So I encourage people to not lose hope and to seek out answers and to learn more about functional medicine and I encourage you to share this podcast with your friends and family on social media. If you liked it, leave a comment we'd love to hear from you and subscribe wherever you get your podcasts and we'll see you next time on The Doctor's Farmacy. Dr. Todd LePine(32:36): Great, thanks Mark.