The Role of Inflammation in Lyme and Chronic Disease with Richard Horowitz, MD

 
Amy Salerno: Founder and medical director of the beautiful Hudson Valley Healing Arts Center in Hyde Park, New York, where he has treated over 20,000 chronic Lyme disease patients. Dr. Horowitz is a Past President-Elect of the International Lyme Disease and Educational Society. In his new book, “Why Can’t I Get Better? Solving the Mystery of Lyme and Chronic Disease,” he explained his full diagnostic and treatment approach for doctors and patients who have complex tick-borne illness. His book actually is to be released on November 17^th, and leading up to that, we also, the Xymogen, have a special promotion for practitioners only if they purchase the book for certain online sites such as Amazon.com. They can submit their receipt to Xymogen and be credited for the book on their Xymogen account. For more information on this book promotion, you can go to Xymogen.com. Again, that’s Xymogen.com. Wait for the banner to appear on the homepage. Click on the flier to download specific instructions to get your free book – Dr. Horowitz’s new book. That’s coming out on November 17^th. The promotion expires on that day, so be sure to check that out. Also, Dr. Horowitz, I want to mention, he was on the Katy Couric show today, which is really exciting. He did a fantastic job, so he’s having quite a day here and he’s going to be presenting for us as well. So without much further ado, I present Dr. Richard Horowitz.

Dr. Richard Horowitz: Thank you so much, Amy. It’s a pleasure to be with you all tonight. For those of you who caught the Katy Couric show, actually, I haven’t really even seen it. I DVRed it to look at it; I have to look at it, but I did get a lot of comments on the internet, and it appears that it went well. It was great to finally be beyond there and show the message on Lyme disease, but what I’m going to share with you tonight is what I’ve discovered in looking for answers for people who are chronically ill, who come to me for Lyme, is that there is one common denominator that we found in a lot of these people who come to us, which is the role of inflammation. It’s interesting because when you’re in medical school, they teach you about inflammation, but nobody really links it up to all the different diseases that we’ve seen. The book that’s going to be coming out in about a month from St. Martin’s Press, “Why Can’t I Get Better?: Solving the Mystery of Lyme and Chronic Disease.” It’s basically my journey over the last 26 years. I’ve actually seen over 12,000, not 20,000 patients, although the way they’re showing it today, it may be over 20 soon. What’s happened is I had – I moved up from Bayside Queens. I moved up to the mountains expecting to be a country doctor, and I moved into one of the Lyme endemic areas in United States. These patients were coming in with EM rashes, and 75% were getting better with antibiotics, but about 25% would relapse or not get better when I gave them their antibiotics. I was always taught in medical school – always get to the source of why people are continuously ill. So, with this journey of 26 years has let me now to write this book. It’s quite interesting because what I discovered is the 16-point model, which would apply generally to most chronic diseases that people have, whether we call it Alzheimer’s disease, whether we call it cancer. I’m going to show you the common denominators that I discovered in simply looking for answers as to why all these people who came to me with Lyme disease continuously stayed ill.

To begin with the disclaimer, you need to understand that those comments that I’m going to give you tonight are based on my own clinical experience. I’m going to show you scientific literature and of course, for educational purposes. And all the practitioners on the line, you need to evaluate these information and comments and of course, my opinions using their own expertise with an assessment for each patient because of course, every patient’s completely different. The information in this presentation is not approved nor endorsed by Xymogen. The content does not necessarily represent the views or brand of Xymogen formulas. And of course, it’s not evaluated by the FDA, and Xymogen formulas are not intended to diagnose or cure or prevent any diseases.

My first disclosure is I’m not a Xymogen employee. I am not a Xymogen customer. I will receive compensation from Xymogen for this presentation. I am a shareholder and on the Board of Advisors, which for me has been really a wonderful experience because we have some brilliant physicians and healthcare professionals who serve on the Board of Advisors. The reason I’m actually on the board is simply because Amy, who has started this presentation, came to me years ago starting to teach me functional medicine, and a lot of what you’re all going to hear tonight is because they have such a wonderful crew on Xymogen, that they will go out and they will actually train doctors. A lot of my training actually has been brought to me by a lot of the doctors who are on the Xymogen board. My other financial interest is my book. Of course, I won’t receive compensation for my book when it comes out. It will be released on November 12^th from St. Martin’s.

So, let’s go to the overview of chronic disease in the United States and why I feel this book really has tremendous interest not just for Lyme, but for a lot of people. According to the CDC, chronic disease accounts for 70% of the deaths and 75% of the health care costs in the United States, and as all of us know, there’s a lot of chronic disease going around. We’re hearing about people coming down with cancer right and left; there’s an Alzheimer’s epidemic; there’s an autism epidemic, and one in 88 kids are now being diagnosed with autism; it’s one in three women who comes down with cancer – one in two men. We’re talking about a tremendous amount of chronic disease and yet, with all of the advances that we have no medical science, no one has really figured out at this point how to get these people better. But when you look at the medical literature, it turns out that inflammation is the number one common denominator in all chronic disease, and I’m going to show this to you in the slides with the scientific literature. Lyme disease is the number one spreading vector borne epidemic worldwide, and it turns out that chronic infections from Lyme and associated tick-borne diseases – what I mean by associated tick-borne diseases is that the majority of people who’ve come to me, when they get a tick bite, they don’t just get Lyme disease, they also get ehrlichiosis, anaplasmosis. In fact, I just saw one kid today who came to see me after eight doctors. His white cell count was below one, he had a low platelet count, elevated liver functions, and the doctors there had never tested him for ehrlichiosis. Once he was finally tested, he was positive. So, we see a lot of tick-borne infections like ehrlichia. A tremendous amount of parasites are getting into people like babesiosis; these are the people that say, “I have day sweats, night sweats, and chills. These people with these parasitic infections, they stay chronically ill, so you just can’t treat the Lyme, you’ve got to treat ehrlichia, you’ve got to treat babesia, you’ve got to treat cat scratch fever like bartonella, mycoplasma. All of these different infections can get into people from one tick bite. What happens is it drives inflammation, and that causes these disabling symptoms where people say: “I have fatigue that comes and goes.” “I have a stiff neck and headache.” “I have a light sensitivity… sound sensitivity.” “I have tremendous memory and concentration problems. I’ll walk into the room and I can’t remember why.” “I can’t fall asleep. I have sleep disorders.” “It’s not like I can’t fall asleep, but I keep waking up in the middle of the night.” “I’m depressed.” “I’m anxious.” “I have these muscle and joint pains that come and go and migrate around my body.” “I have tingling, numbness and burning that comes and goes, and migrates around my body.” “I have chest pain and shortness of breath.” All of these symptoms are symptoms of chronic Lyme disease and what I call “Lyme and MSIDS,” meaning these are the symptoms that happen when Lyme and multiple tick-borne diseases get into your body. And what do they do to your body? It causes inflammation. So, infection, inflammation, and the subsequent immune dysfunction that happens from inflammation and chronic infections causes these people to stay sick, and what I’ve discovered is, is when you treat the infections and can take down the inflammation and regulate their immune system, these people who’ve been to 20 doctors to say, “I’m still ill; no one can help me,” you can help them recover their health.

I’m going to show you today, and this is what’s described in the book in great detail. The book is 526 pages. It’s a hard-cover edition, and it’s going to describe in detail this model – multi-factorial reasons why people stay chronically ill called “MSIDS (Multiple Systemic Infectious Disease Syndrome),” and it will show you how multiple factors on the MSIDS map can be addressed to help decrease inflammation. Now, what are these 16 factors? Well, this is literally like having. 16 nails in your foot like I was describing in Katy today. You go into the doctor with pain in your foot. The doctor looks for reasons and finds maybe one of two nails. Here are the 16 nails that could be in someone’s foot that causes them to be ill. Some people may have four nails; some people may have eight, but the point is if you don’t discover all the points on the MSIDS map that’s in front of you, these people will not completely get better. As I said, under 1, infections, we start with eight bacterial infections: Lyme disease, ehrlichia, bartonella, mycoplasma, Rocky Mountain spotted fever, typhus, tularemia, q-fever. We find all these infections that get into these chronically ill people. B is parasites: babesia and other piroplasms. There may be other infections under parasitic infections like amebia, giardia. We’re finding a tremendous amount of intestinal parasites at this point, and this year, what we’ve discovered and is discussed in the book, is that people have babesia who also have parasites like toxoplasmosis, many of them also have intestinal parasites, so when you treat their intestinal parasites, many of these Lyme symptoms tend to get better. So, parasites are playing a huge role in keeping people chronically ill. We also have viruses like Epstein Barr, herpesvirus 6, cytomegalovirus. Sometimes, other viruses that are in the ticks like the Heartland Virus; this is a virus now that causes low white blood cell counts, low platelet counts, and elevated liver functions, just like ehrlichia and anaplasma, except it doesn’t respond to doxycycline. That virus is now in ticks found in the Midwest. Finally, the Powassan virus, which is now killing people, and within 15 minutes of a tick bite, you can get this virus into your body; it can cause an encephalitis with brain swelling, and the mortality rate is now up to 30%. I discussed this on the New York Times blog about a month and a half/two months ago. So, all of these different infections can get into your body from a tick bite. And then there’s candida and other fungi, which may exist already in your body. The antibiotics may make it worse. So, we have to look at treating all these different types of infections if people don’t get better.

The second nail on the foot is the immune dysfunction. When these infections get in the body, it causes a non-specific stimulation of the immune system, so you get a positive antinuclear antibody, a positive rheumatoid factor, and it’s much worse in people who are HLA DR-4 positive. What that means is you don’t necessarily have has lupus if you’re ANA positive; you don’t necessarily have rheumatoid arthritis if your rheumatoid factor’s positive. You treat these infections and all of a sudden, these markers will go back to zero and the people get better. But unfortunately, they sometimes go to the rheumatologist and they’re told, “You have lupus; use some steroid,” “You have rheumatoid arthritis; here’s some Hekla Lava.” But they don’t know that they may have these tick-borne infections.

The third piece, that we’re going to discuss tonight in the webinar that I’m really going to focus on, is inflammation, which means that there are these inflammatory molecules, these inflammatory cytokines, tumor necrosis factor-alpha, interleukin-1, interleukin-6 – these are created when you have all of these infections that get into your body. What do they do to you? They cause something called “the sickness syndrome,” which has been described in the medical and the psychological literature. What is the sickness syndrome? Well, when you get a flu, you feel tired and you feel achy, you feel foggy and want to go to sleep; that’s the sickness syndrome, and it’s caused by these inflammatory cytokines. It turns out that many of the symptoms you see in Alzheimer’s disease with brain function are caused by the cytokines. The symptoms we see on the Lyme disease and tick-borne diseases are caused by these inflammatory cytokines. So, what I’m going to discuss with you tonight is how do you lower the inflammation in the body, how do you detox the body and get these cytokines out of the body, and what are the overlapping factors on the MSIDS model that drive inflammation. So for example, the fourth point, these chemicals that get into your body like heavy metals, they will cause inflammation in the body with free radical/oxidative stress.

The fifth point, allergies, for example, to foods that you might be sensitive to – they will cause leukotrienes and cytokines to be created causing the immune dysfunction and causing inflammation in the body.

 

Nutritional deficiencies, the sixth point, like zinc deficiency will cause increased inflammation and cytokines to be released. If you have inflammation and oxidative stress, it affects the mitochondria, the part of your body that makes energy. If you don’t heal the mitochondria, the energy may not get better. And then your psychological issues, neurological dysfunction. A lot of endocrine disorders, we find, because the Lyme affects the hypothalamic-pituitary axis, where these cytokines will basically affect the HPA axis and will decrease your adrenal function, will cause some men to have very low testosterone levels even in the 20s, and a lot of the doctors when these people come in with fatigue and memory problems, they don’t think that there may be adrenal disorders or other hypothalamic disorders.

The 11^th point is these Lyme patients don’t get to sleep. If you ever get a patient that comes to see you and says despite Ambien, despite Lunesta, despite melatonin, despite your best efforts, they don’t get to sleep, you can almost be sure that you may have Lyme in back. In background because Lyme is one of the worst infections, where people just do not fall asleep. Why? Again, because of these cytokines, and in fact, when they don’t sleep, it causes an elevation in interleukin-6, which is one of these inflammatory cytokines, which makes all of their symptoms worse.

The 12^th point, autonomic nervous system dysfunction and POTS, we find that the Lyme affect the autonomic nervous system. For example, these people come in they’re tired, they’re dizzy, their memory’s off, but it’s not just you treat them with antibiotics. If you don’t get your autonomic nervous system back up and functioning by giving them salt, giving them fluids, giving them phenylephrine and midodrine, maybe beta blockers if they have too much norepinephrine with palpitations, these people will not feel better.

The 13^th is GI disorders. We find a lot of leaky gut in these people that drive inflammation, a lot of parasites as I was describing.

The 14^th is elevated liver functions. This young man that came in today, he had an AST and ALT in the 200th range, and the doctors he saw never ran a hepatitis B and C screen; they didn’t check the hemochromatosis with ferritin. In other words, they didn’t check him for all the reasons why someone may come in with elevated liver functions. In my book, every one of these points that I’m describing to you is about 20 to 25 pages; it’s all based on solid internal medicine and has an integrative approach. For example, the doctors that have never learned integrative medicine, they will read this book and they’ll learn it, and for the doctors that do integrative medicine, it will bring you back to internal medicine roots. But these are the 16 points that are described in detail, which is why many of these patients do not get better. I’ll discuss with you later on the webinar on pain syndromes why people have pain and what we can do about it from an integrative perspective. So, in my book, “Why Can’t I Get Better?” expected to be released by about a month’s time from St. Martin’s Press, and you can preorder it on Amazon and on all the major book sellers at this point in time.

So, the reason why we’re having a problem with chronic diseases and the reason I’m presenting to the MSIDS model and why I think it’s so important for chronic diseases of the 21^st century is that we were all taught in medical school “Pasteur’s postulate:” there is one cause for one disease. Well, that is an old paradigm. The advantage of the model, that I’m showing you in seeing over 12,000 chronically ill people, is it’s taking into account simultaneous overlapping factors that are causing the same symptoms. For example, a patient comes to you with fatigue, if you look at the 16-point MSIDS model, you’ll see that it could be not just one infection, but multiple infections as we talked about – immune dysfunction, inflammation with cytokines being released causing the sickness syndrome. These people may have environmental toxins like heavy metals, and when they do a six-hour urine DMSA challenge on many of these people, they do show a positive for lead and mercury. The best majority of my people have detoxification problems with inadequate amounts of glutathione. When I give people IV glutathione in my office 2,000 mg, up to 70% of these people will say their fatigue, their joint pain, their muscle pain, their memory, concentration problems, their moods will improve within minutes to a half hour to an hour simply by detoxifying them and getting these cytokines out of the body. I didn’t give them an antibiotic; all I did was detoxify them. One of the points you want to take home tonight of this MSIDS map that I’m giving you is that detoxification is extremely important in getting these people better, and it’s missed by many doctors who don’t understand integrative protocols. Again, these hormonal problems are very common; 40% of my patients have adrenal insufficiency; they don’t get better if you don’t pick up their adrenals. They have vitamin deficiencies that we can pick up not only by testing for B12 and folic acid, by looking for methylmalonic acid and homocysteine, and many of them have mineral deficiencies up to 25%. So, if you look at all of these disorders – sleep disorders, mitochondrial – all of these disorders can have an effect on the train of the body explaining why the fatigue doesn’t get better. When you treat all of them simultaneously, these people, in fact, do get better.

So, when we look at the scientific literature at a lot of Lyme and chronic disease and inflammation, we see that there’s a lot in the scientific literature about infection, immunity and inflammation. We have inflammation that affects the central nervous system. In fact, how we can find elevated peroxynitrite levels with the nitric oxide pathway’s stimulated in chronic fatigue syndrome, in posttraumatic stress disorder, in fibromyalgia – we’re just going to bring that to this common denominator that there’s free radicals and oxidative stress driving cytokines with even the nitric oxide pathway being involved, and once we can regulate that pathway, people will get better.

If we look at a disease like fibromyalgia, the reason many of the Lyme patients come to me – and they’re told by their doctors that they have fibromyalgia, they have chronic fatigue – is that they suffer exactly from the same immune dysregulation. They have decreased anti-inflammatory cells; their IL-10 is down; they have abnormal helper/suppressor cell ratios; and they have elevated pro-inflammatory cells like tumor necrosis factor-alpha, interfuron gamma, and IL-6. When we look at chronic pain and fatigue syndromes, we see these same neuroendocrine features whether you call it “chronic fatigue,” you call it “fibromyalgia,” the same neuroendocrine problems, the same inflammatory markers are found throughout where there is excessive proinflammatory response. So, Lyme disease will cause inflammation in the body both in the peripheral nervous system and central nervous system. If a patient comes to you and says, “I have tingling, I have numbness, and I have burning,” after an EM rash, that means it has gotten into the peripheral nervous system, and 30 days of doxycycline is not going to cure that patient. If they say to you, “I have a stiff neck and headache,” “I have light sensitivity, sound sensitivity, brain fog, memory concentration problems with an EM rash,” it means it’s gotten into the central nervous system. Again, 30 days of antibiotics normally is not going to cure that patient. Now, why do we see these different symptoms? Well, the signs and symptoms actually depend on the different genospecies. There are 100 strains of Lyme disease in the United States and 300 worldwide. So, we mainly see Borrelia sensu stricto in the United States, but we are seeing some afzelii and garinii also in the U.S. But in Europe, they’re seeing afzelii, which causes their skin lesion, which causes acrodermic chronica atrophicans (ACA) and they have Borrelia garinii, which is neuroborreliosis. We don’t see so much because as I said, it is starting to show up in the U.S. But what’s very specific with Borrelia, these spirochetes express lipoproteins on the outer surface proteins of the cell wall that are pro-inflammatory, and more than 8% of the coding sequence of the be 31 strain is presumed to be this lipoprotein sequences. What they do is they attract neutrophils; they’re 50 to 500 fold more active inducers of cytokines of these inflammatory molecules and other organisms like E. coli, and molecular mimicry will occur in the peripheral nervous system where you get your antibodies trying to kill Borrelia, and instead of killing the Borrelia and the flagellin (the tail), it will cross-react with your neurons and causing neuropathy. That’s why these people will get these neuropathic symptoms; that’s why they have these MS type presentations where they get demyelination because in some people genetically, your immune system tries to kill the Borrelia and there’s a molecular mimicry with the Borrelia and your own myelin sheath, and that’s where you get these MS type presentations with neuropathy.

So, when you look at chronic infections and inflammation, these agents create inflammation through various pathways – cytokines like IL-1, IL-6, TNF-alpha, nitric oxide and its metabolites. What this inflammation does in the body is it creates free radicals; it increases oxidative stress, which damages cell membranes, mitochondria, and nerve cells. Some of these infectious agents also produce neurotoxins like quinolinic acid, and that’s why when these Lyme patients have memory and concentration problems, it’s not enough to just give them antibiotics, you’ve got to lower the load of these neurotoxins in their body. You can also get autoimmunity, so it’s not that doctors here and some of the other doctors are wrong that you don’t get autoimmune reactions with Lyme; in fact, they’re correct – you get it all the time. The difference, as I’m going to show you, is that Lyme and other infections like mycoplasma will also cause this same type of autoimmune reactions. We see these same pathological problems and biological effects whether we’re talking about persistent Lyme, whether we’re talking about autoimmune disorders, chronic fatigue syndrome, fibromyalgia, environmental illness, chemical sensitivity, autism spectrum disorder. All of the same diseases that we’re talking about here are linked up with the same biological effects of cytokines and the same ideologies. If you go to an autism conference, you will hear the doctors talk about exactly the same things, and they’re going to tell you about the MSIDS model, that food sensitivities and leaky gut, heavy metals, environmental toxins, detox problems, inflammation, infections. When they treat these kids with autism spectrum, many of these kids get better just by addressing the same 16 points on the MSIDS map. So, if you want to mitigate these effects, what it comes down to is you’ve got to treat what they call the 3 I’s (infection, immune issues, and inflammation); you’ve got to support the detox pathways; you’ve got to balance out the hormones because many of these people have low adrenal hormone, and low male and female hormones; you’ve got to address their nutritional deficiencies, food allergies; you’ve got to get them to sleep; and you’ve got to pull out a lot of these heavy metals and environmental toxins, which drives inflammation. Once you address all of these factors on the MSIDS map, we will see these people get better.

The immune dysregulation – this is the second point on the MSIDS map, and the reason we get a lot of this immune problem with Lyme is Lyme produces these parts of the DNA called “blebs.” These are shed particles from Lyme, which are plasmids. They’re very highly stimulatory to the immune system, and they convert host cells into targets for the immune system. But then what happens is you get these false positive antinuclear antibodies and rheumatoid factors with autoimmune markers. The people who are much worse are the ones who are HLA DR2, 4 positive, where they get much more pro-inflammatory cells. Again, both Lyme and autism spectrum disorders – we see exactly the same immune dysregulation, and we know that these systemic infections with inflammation will affect neurodegeneration in both Lyme and autism spectrum disorder.

These inflammatory mediators are also involved in neurotoxicity. We know that in Alzheimer’s disease and in other central nervous system diseases, you have microglia in your brain that are activated by beta amyloid and these proinflammatory cytokines. Once your microglia in your brain get activated, what do they do? They in turn release more of these pro-inflammatory cytokines that lead to neuronal cell death and dysfunction, leading to the sickness syndrome that we’ve been describing. So, you’re going to get glutamate-induced excitotoxicity; you’re going to have a problem with the hippocampal campus for memory, for creating new neurons; and we know that Lyme patients, as well as Alzheimer’s patients, have elevated levels of these inflammatory cytokines in the central nervous system, and they even showed in Alzheimer’s patients, if you lower down TNF-alpha, their memory gets better just by lowering down inflammation. So, these pro-inflammatory cytokines are playing a huge role in people with central nervous system diseases, and it’s probably why low-dose naltrexone described in my book in great detail and I’ll talk to you about in a little bit; what it’s probably doing in helping Lyme patients is it’s modulating levels of TNF-alpha and some of the cytokines that are making these people sick.

When we look at the nitric oxide pathway, it is a common etiological mechanism for chronic fatigue, chemical sensitivity, posttraumatic stress disease. So, the above illnesses share many of the many symptoms, but they don’t have to be caused by Lyme. You can get a viral infection, other bacterial infections, emotional trauma, exposure to a volatile organic solvents or pesticides. Any factors like this – any trigger – can cause you to get the nitric oxide pathway to be stimulated. It will affect NMDA receptors in your body, create the production of oxidant products like peroxynitrite, which stimulates your immune system and causes these inflammatory molecules. And we know that Lyme can increase these inflammatory cytokines, but what about the other common infections I’ve talked to you about? Well, the most important one that I see that drives inflammation apart from Lyme is mycoplasma. It turns out in a study from the University of New Haven – I was doing the study whether it’s not yet in publish – that she’s finding mycoplasmas in the ticks, mycoplasma from men cans that causes Gulf War syndrome, mycoplasma pneumonia, mycoplasma genitalium. All these different mycoplasmas are found inside the ticks, can get into the body. We don’t really know the transmission rate, but many people have chronic mycoplasma infections anyway. What they do is they interact with the B-lymphocytes in your body; they modulate the immune system creating autoimmune reactions and rheumatoid diseases; they further increase these pro-inflammatory cytokines like IL-1, IL-2 and IL-6; and other coinfections like Brucella and mycoplasma have been found in a lot of people with chronic fatigue syndrome in the Midwest, as well as in people with Gulf War syndrome and in ALS. So, it’s linking up many of these chronic diseases – this mycoplasma and other chronic infections.

So, mycoplasma, interestingly enough, has also been found in inflammatory bowel disease and in Crohn’s disease. I think what we’re going to find, as the years go on, is that many of these chronic diseases that we’re calling autoimmune are in fact being driven by chronic infections causing many of these autoimmune manifestations, as well as inflammatory molecules and certain environmental toxins like mercury, also causing over 800 autoimmune reactions in the body.

Lyme and gastrointestinal disorders – I think there is a role here for bacteria in health. I’ll tell you about this at the end of the talk regarding probiotics and why probiotics is so important. What many of you may not know, and this is described in my book in detail, and it was fascinating while I was doing the research for the book, is that if you take lactobacilli or you take bifidobacteria, they induce differential interferon profiles in your body, meaning they’re going to affect the cytokines in your body. Lactobacilli, in some cases, can increase your cytokines, and bifidobacteria will decrease your inflammatory cytokines. So, they’re now showing that the role of the gut bacteria is extremely important. For example, you probably know now just we’d see death or we’re using this, now, you can even take someone who is thin, we can take bioflora from them, transplanted that gut microflora into someone who’s obese and we can make them thin, just like transplanting gut microbiota into those people. So, there’s going to be a role in the future for manipulating lactobacilli and the bacteria in the gut, and this is described in the book and it’s fascinating; it’s why we needed to look carefully at the gut composition and the probiotics we’re taking every day.

Now, I talked to you about sleep increasing inflammation. Lyme patients don’t sleep. Unfortunately, impaired sleep will affect your immune functioning. Most of the chronic inflammatory diseases we see with age and stress, such as rheumatoid arthritis and fibromyalgia; these people also don’t sleep, and it will cause inflammation.

Food allergies will cause inflammation. We find that a large number of our patients have leaky gut at this point. Many of them have gluten sensitivity. Many of them have candida. It turns out that when you have them avoid gluten, when you clean out your leaky gut and get rid of candida, many of these people, their fatigue gets better, their headache gets better, their allergies get better. I’m a perfect example. I have allergic rhinitis; I had asthma most of my life. I didn’t know I had a dairy allergy. Once I got rid of dairy in my diet, my allergies were much better and I don’t have to use asthma sprays. And we find a large number of our patients will get reactive hypoglycemia and they will get these types of manifestations of fatigue, headache, irritability, concentration problems irrespective of Lyme just from eating foods that they are sensitive to. So, what food sensitivities will do is exactly the same thing that Lyme and infections do. They will trigger mechanisms by causing the cellular activation and cause mediator release, again, with cytokines, with interleukins. So, the point in getting to in this talk is if many of these nails in the foot that I’m telling you about, whether it’s food, whether it’s sleep disorders, whether it’s infection, whether it’s heavy metals and environmental toxins, all of these different factors are driving inflammation, and inflammation is what’s causing the symptoms in many of these people when they say, “I’m tired,” “I’m achy,” “I’ve got headaches,” “I’ve got memory problems.” So, I didn’t realize years ago that heavy metals were playing a major role in driving oxidative stress and increasing pain and MSIDS, and I did a study on heavy metal burdens and Lyme patients back 10 years ago that I presented at the 16^th International Lyme Conference. We found when we were doing the study that of course, there are ubiquitous in the environment accumulating slowly. Most doctors don’t really think of toxicity unless there’s acute poisoning. But the problem with these heavy metals is they cause any symptom such as fatigue, muscle and joint pain, headaches, paresthesias, memory loss, confusion, psychiatric abnormalities – the same symptoms we see in chronic Lyme and MSIDS are the same symptoms that can be caused by heavy metals. And most of the time, doctors who are trained in internal medicine like I was, don’t usually do regular tests. What they do is they produce oxidative stress, reactive oxygen species, they drive the inflammatory pathways, and the pain in neurodegenerative disorders will be much worse. What they also cause is they cause nutritional deficiencies. They cause magnesium deficiency; we need magnesium in 300 detox enzymes in the body. Many of my Lyme patients say they get muscle spasms, they have tremors, they have anxiety, they get Raynauds phenomenon, they get arrhythmias. You can reverse it in some people simply by getting their magnesium backup. We don’t just check the serum magnesium, we check their red blood cell magnesium since 99% of the magnesium is intracellular and some people, when we replace the magnesium, it’s miraculous how well they feel. We find copper deficiency, which is necessary in superoxide dismutase, necessary for decreasing free radicals, for detoxing chemicals. We find that a lot of these things will cause oxidative stress.

So, the reason, that I discussed in the beginning of this talk about oxidative stress and MSIDS, is if you look at oxidative stress and how it relates to all these different diseases that we come up with chronic diseases in the 21^st century, this has all been linked in the medical literature, whether it’s Alzheimer’s, Parkinson’s, heart attacks, rheumatoid arthritis, psoriasis, scleroderma, diabetes, cancer, cataracts, asthma, atherosclerosis, the one common denominator is free radicals at oxidative stress. So, we’ve to deal with oxidative stress if we’re going to get these people better. What the people tell me when they come to see me, and the way I know that it’s Lyme and I’ve got to deal with the MSIDS map, is what they would say to me. This is how you’re going to take the history from these people. They’re going to tell you that the pain comes and goes with good and bad days, and it migrates around the body. They’re going to tell you their muscle and joint pains – they have good days and bad days; one day it’s in the elbow, three days later it’s in a hip. They’re even going to tell you the neuropathic pain quite often will come and go and migrate, with tingling, numbness, and burning, whether it’s in the face or their extremities. That doesn’t happen with carpal tunnel; it’s in one place. So, that’s very classic for Lyme, where it comes and goes, and migrates. Women will also tell you it’s influenced by their hormonal cycles; they will tell you right before, during, or after the menstrual cycle, their symptoms are much worse or they may get Jarish-Herxheimer flares just like you get when you’re giving people antibiotics for Lyme. If you happen to give a patient, that they don’t know they have Lyme, an antibiotic for let’s say a sinusitis, urinary tract infection, they may tell you, this pain that they had for months or years gets better or gets worse from using the antibiotics. If it gets worse, it’s probably consistent with the Herxheimer reaction. If you have very resistant pain that’s resistant to standard treatment modalities – you’ve given them NSAIDs, you’ve given them serotonin reuptake inhibitors like Cymbalta, you’ve given them neuroleptic medications like Neurontin, you’ve given them narcotics, and they still have pain – you can almost be sure that these people probably have Lyme, they have bartonella, they have heavy metals, and they’ve got a lot of oxidative stress because that’s what I found in treating over 12,000 people who come to me with pain. The one easiest way that you’re going to be able to tell that people have Lyme, which is in my book, is to use a multisystemic symptom questionnaire, and this is what it looks like in the book. This is on page 38 of the book, I believe, and what I did is we took the questionnaire that we give to patients and we score them. Patients are going to fill out this questionnaire; you can give it to your patients. They’re going to say that, “Sometimes I have it,” “Most of the time, I have this symptom,” or “I have it all the time.” They’re going to fill out this 38-form. They then fill out in the Section 2 the frequency of whether you think they have Lyme disease or not; for example, “Have they had a tick bite or rash?” “Do you live in a Lyme endemic area?” “Has someone in your family have Lyme?” “Do you experience migratory muscle and joint pain?” They’re going to get a score points for each of these symptoms. And then in Section 3, you’re going to ask them about their physical health, about their mental health; they’re going to get a score. Lastly, on Section 4, if on the first page, they rated 3 for fatigue, memory problems, joint pain, then they’re going to get an extra point. We found out in our patient population if they scored 46 or higher, they were two standard deviations above the mean, meaning they’re very highly likely of having Lyme. If you give this questionnaire to people or you give it to your patients, they read the book, and they score 46 or higher, and they read the symptoms in the book, and they read the patients’ stories, you could almost be sure by the time you’re finished reading my book, if you don’t know you have Lyme disease, believe me you don’t have it by the time you’ve read this book. What I did on the Table 2.1 on page 68, for people come in with complex symptoms, they don’t know what’s wrong; this goes on for about 10 pages for every symptom that someone comes in with. For example, say something comes in with day sweats, night sweats and fevers, I go through differential diagnosis for every possible medical condition. Well okay, it could be Lyme, but maybe it’s babesia, or maybe you went to India and it’s malaria. Drenching night sweats could be Brucella, maybe you have hyperthyroidism, maybe you have early menopause, tuberculosis, non-Hodgkin’s lymphoma – all of these things can cause night sweats. So, what you do is you look at the tables on page 68, 69, 70 and you link up every symptom you have to possible medical conditions, so you can go through a differential diagnosis to figure out what it could be. And then you’ll see on the third column, lab testing to consider. So, you can work with your doctor to have the best possible outcome in these complex cases. What this comes down to, is in figuring out how to work with patients and what have really gotten them most ill, is you’ve got to treat all the different forms of the Lyme using cell wall drugs, cystic drugs, intracellular; I described this in detail in the book including integrative protocol with herbs in great detail, and for the integrative practitioner and doctors, there’s a whole addendum in the back of the book just for healthcare practitioners that explains the dosing and how to do this for patients. We’re also going to treat biofilms, which are now showing up in the literature, which may be a reason we can’t get rid of Borrelia so easily. All of the common infections are described in great detail in the book, and you’re going to address the 16-point MSIDS model.

When we look at MSIDS and pain in the role of these 3 I’s throughout the medical literature, you’ll see that tumor necrosis factor, interleukin-1, interleukin-6 – all of these immune problems in Lyme patients were causing them to stay ill and be sick. What I have found to be fascinating – it’s also described in the book in detail – is the book describes how you’re going to treat these people with chronic-resistant fatigue and pain by looking at a model for Herxheimer reactions. And what I found is, I call it “shutting down the faucet,” meaning shutting down the faucet of creating cytokines, and opening up the drain and getting rid of these toxins. So, the first thing you need to do to these people who are ill, who have fatigue and pain, is alkalizing. Patients who have tremendous pain and herxes, if you give them two Alka-Seltzer Gold, you give them some sodium bicarbonate, buffered vitamin C, lemons and lime water – by shifting the PH, many of these patients (up to 70%) will tell you their pain gets better because when they’re sick, they get a lot of acid byproducts. The second point is you’ve got to get rid of these neurotoxins from the body; IV glutathione is certainly more effective, but you can use oral glutathione; I found if I use a liposomal glutathione between 1,500 to 2,000 mg and I alkalize them, 70% of patients will tell me in the next several hours that they’re much better; we also use other supplements to support liver detox like milk thistle, phosphatidylcholine, sometimes enemas, intestinal detox with charcoal bentonite clay and zeolite, and you’ve got to keep the colon moving and flush them out with increase fluids. You also want to shut down the production of cytokines by using drugs like low-dose naltrexone. I have a big section in the book – all the scientific references where LDN has been talked about for MS, for chronic disease, for fibromyalgia, we started 2 mg at bedtime for a month, then go to 3 mg at bedtime for a month, and then 4.5; this is very useful for taking that overstimulated immune system and immune dysfunction, and regulating it, and decreasing the stimulation of NF-kappaB, which I’ll show you in a second, is a switch inside the nucleus, which creates many of these inflammatory cytokines, and then you’re going to give them antioxidants like alpha lipoic acid, resveratrol (which is found in red wine), curcumin, broccoli compounds like diindolylmethane and sulforaphane and glucosinolate, OncoPLEX from Xymogen (which works on the Phase I/Phase II liver pathways). You’re going to replace the minerals because as I said, if the detox is not working properly with the pathways, these people are not going to get better; so, you’re going to give the magnesium, you’re going to replace their zinc and copper in a good multi-mineral like Mineralex that I’ll describe to you. Finally, you’ve got to open up the drain with drainage remedies; some great drainage remedies I use are the Pekana drainage remedies that come from Germany, such as Itires for lymphatic drainage; we’ve used things like Sydetox from Syntrion, with extra fluids, some exercise and infrared saunas – very, very helpful for getting these toxins out of people body and getting them to sleep.

Now, we’re going to go on and discuss finally, the last part of the talk, the nutritional support of what we’re going to do for these people who have Lyme MSIDS. We’ve already said that they got oxidative stress, they got lots of inflammation; we’re treating their infections; we’re opening up the detox pathways, pulling out the metals and toxins; we’re replacing these nutritional deficiencies; we’re going to get their gut in order, get rid of those allergic foods; balance the hormones, and get them to sleep. These are some of the six points of the 16 points on the MSIDS map, which are very important for getting these people better with pain.

Now, one thing I’d like to address, and it’s fascinating when we look at how to get these people better, is the anti-oxidative response and element genes in the body. There’s a mechanism in the body that these genes and something called “Nrf2,” which helps with inflammation, and Nrf2 is in the cytoplasm of your cells, and it regulates your redox balance and your stress response. So, if you’ve got these free radicals and oxidative stress, it’s going to affect Nrf2. Normally, in an unstressed state, it’s anchored in the cytoplasm by an inhibitor, Keap 1. But if all of a sudden, you ‘ve got oxidative stress, Keap 1 gives up its inhibition of Nrf2; Nrf3 goes into your nucleus; it binds to these ARE genes, which are DNA binding sites that are going to activate your phase I and phase II enzymes. That’s what’s going to do is it’s going to enhance your detoxification, decrease your inflammation, and it’s even been shown in the medical literature to inhibit cancer growth. So, this mechanism would explain why the medical literature always talks about the beneficial effects of eating broccoli and cauliflower, and all of these cruciferous vegetables because these are the same detoxifying phytochemicals that act on ARE gene activation in the body. And we can take them as nutritional supplements like sulforaphane, resveratrol, curcumin, and green tea extract. Sulforaphane is something I take every day; I give it to many of my patients; this is called “OncoPLEX” from Xymogen, and it’s broccoli seed extract; the reason it’s such an amazing product is it acts like an antibiotic on Helicobacter, it acts on inducing the phase II response, it’s actually the strongest nutritional supplement for opening up your phase II liver pathways (stronger than any other nutritional supplement that’s ever been out), it has antioxidant effects, it’s an anti-inflammatory, and in the medical literature, it’s been shown that tumor inhibition; of course, we can’t say it’s going to stop you from getting sick, but this is some of what’s described in the scientific literature. Resveratrol, with alpha lipoic acid for antioxidants – these will also affect the sirtuin genes in the body (which deal with inflammation), these will help increase your mitochondria biogenesis, they’re lower down your oxidative stress (increasing your energy); so, these are all biochemical pathways that we can manipulate in the body using nutritional supplements.

Resveratrol, sirtuins, and Nrf2. The resveratrol, the red wine extract, works with sirtuin genes, which are the genes in your body that are related to age-related diseases like cancer, heart disease, osteoporosis, diabetes, and neurodegeneration. And so is pterostilbene, which is a naturally occurring phenolic compound, which is from resveratrol; it has tremendous anti-inflammatory and antioxidant properties, and it will work on the expression of Nrf2. So, that is why we use this in a lot of our patients because we want to get the mitochondrial function back in order and we want to help them with their neurodegenerative disorders.

I use a lot of curcumin in my practice to reduce inflammation. It’s a wonderful herb that’s been shown in the scientific literature with many references, helping to decrease these inflammatory molecules, these cytokines that we’ve been talking about. What it also does is it translocates Nrf2 into the nucleus, activating these ARE genes. So, the molecules that are decreased by curcumin include phospholipase, lipooxygenase, leukotrienes, thromboxane, prostaglandins, the nitric oxide pathway, TNF-alpha. All of the things we talked about are decreased by curcumin, which explains why many of my patients will use curcumin combined with OncoPLEX with sulforaphane with many of these inhibitors because I want to work these pathways to be able to decrease these inflammatory molecules.

One of the main pathways we want to work on is decreasing the activation of NF-kappaB. So, just like I talk about ARE gene activation, the NF-kappaB is inside the nucleus. It’s one of the main mediators of inflammation, and when we give glutathione, when we give alpha lipoic acid, when we give antioxidants, it blocks the effect of turning on NF-kappaB, subsequently decreasing inflammation and decreasing the production of IL-1, IL-6, and TNF-alpha. So, what do you want to do for your patients for inflammation and pain? We’re going to use antioxidant therapies like alpha lipoic acid, glutathione, resveratrol, curcumin. So, we’ll use LDN; we’ll use things like N-acetylcysteine, glycine and alpha lipoic acid, which all help drive the production of glutathione, which is tremendously beneficial for my Lyme and MSIDS patient and helps them with their pain, fatigue, and their brain fog. And it looks again at the mechanisms of action like we talked about – it’s decreasing oxidative stress, it’s decreasing your stimulation of NF-kappaB, lowering down inflammation and these cytokines in the body.