Hello, and thank you for taking time out of your busy schedule to join us today. My name is Dr. David Blyweiss, Chief Medical Officer for Cell Science Systems. The purpose of this webinar series is to broaden your understanding of the immunological differences between innate and specific immunity and how those differences manifest in disorders ranging from gluten, and other food sensitivities, to more severe manifestations, such as celiac disease. In the upcoming lecture titled, The Leading Edge of Functional Neurology, Board Certified Neurologist, Dr. David Perlmutter will discuss the critical gut/brain connection and the role that gluten plays in the development of chronic neurologic, degenerative diseases.
Be sure to stick around at the end of the lecture, as I’ll be giving you information on Cell Science Systems, innovative testing. In this, his first lecture, The Leading Edge of Neurology, Dr. David Perlmutter explains how we can positively impact the increasing epidemic of neurological disease through lifestyle, which not only induces changes in our physiology, but in our DNA epigenetics, as well. We learn that prevention of oxidative damage to our brain, and hence the mitochondrial failure causing neuronal death, ultimately resulting in brain dysfunction is not available through prescription drugs, but simply by what we eat and how much we move. Sit back and relax. You’re going to enjoy this, and now Dr. David Perlmutter.
Hi, everyone. Well, this is the final push. So I want to tell you that this idea of being, that we have inherited this genome, that we have to realize it, directly relates to how we interact with our environment. And I began thinking about this notion that we’ve inherited this genome that cannot rapidly adapt to things to which we are exposed. I started thinking about that a few years ago, actually when I was 15. And I wrote this article in 1971 when I was 15. About adapting to the future, our genome. And these were things that puzzled me, as a 15-year-old.
And I wrote that perhaps humans will change rapidly in the next centuries to adapt himself or herself to this environment of cans, concrete, and shattering noise. Our generations are each contributing to the evolution of pollution resistant lungs, but what about the people of today who are stuck with the outdated machinery? And that’s what I was thinking about when I was 15, I guess, prior to going to college, and forgetting about all those kinds of things. But I’d like to look at it just briefly. Then we’re going to get into some really good stuff, just trends in lipids and lipoproteins, and really what the article looked at, which I thought was really interesting, is an assessment of lipid lowering drugs.
The use of lipid lowering drugs just exploding on the scene, and I thought it was interesting in this period of time, from 1988 until more recently. If you’re holding stock of Novartis or somebody you’re a happy camper, for sure. But look at the trends in diabetes, as well. So I guess this means more drugs for diabetes. But there’s an interesting parallel, isn’t there? Let’s get back to the notion of ketogenic diet, and again, what I’m discussing here is a brand new revolutionary diet plan for you, and your genome. It’s only been what your genome has been exposed to for tens of thousands of years, and in fact, your genome was selected based upon this environmental influence. This is a study looking at the laboratory model, the super oxide dismutase model of ALS, amyotrophic lateral sclerosis, or Lou Gehrig’s disease.
And just looking at this is the transgenic mouse that gets Lou Gehrig’s, has this super oxide dismutase variation that leads to this neuronal dropout. But in that same genetically determined mouse who goes on a ketogenic diet, look at the neuronal population. This is control. This is the desodene mutant mouse, and then putting that same mouse on a ketogenic diet, an incredible example of what happens when you salvage mitochondrial function and reduce free radical influence. So when I put my ALS patients, who I see probably three or four times a week now on a ketogenic diet there aren’t any studies yet, I can tell them about. But this is my rationale for doing it. We’re targeting mitochondrial function. This is time to failure, in other words not able to ambulate, on the ketogenic diet.
Significantly improved, extended, rather in the mutant mouse that is on a ketogenic diet versus the mutant mouse that did not go on this diet, and this is maintenance of body weight, significantly preserved in targeting mitochondrial function by giving fat not carbs. Well, how do we enhance ketones? Again, coconut oil, medium chain triglyceride oil and a carbohydrate restriction. This is what I do in my clinical practice. It’s why we prescribe things like MCT oil. Then we follow using keto-sticks. I tell patients, “We’re going to put you on a very, very expensive trial here, and it’s going to cost you about $6 bucks a year to buy these keto-sticks.
And interestingly enough I, from time-to-time test myself to see how ketotic I am. You measure it like you measure the chlorine in your pool, if you have a chlorinated pool, and I found you’ve got to be sure to pee on the right end. Because if you pee on this end, nothing happens and you go, “Oh, my God.” You wake up your wife and then say, “Something’s wrong. The whole diet’s erroneous.” Anyway so Dr. Pasinetti was talking earlier about the trans-barrier migration of plasmas of stem cells, seemingly induced by gliomas which is pretty powerful conceptually in and of itself. And I’d like to tackle that idea of glioblastoma, and look at perhaps what else can be done, in this really devastating condition.
Let’s talk about glioblastoma, a very horrendous, aggressive type of brain tumor, and unfortunately it is the most aggressive and most common primary brain tumor of adults and children. If you have the diagnosis, you might live for one year. That’s the median survival. Living for three years, your chances of that untreated are about 3% and what is the standard of treatment? Radiation, chemotherapy and, of course, steroids because of the swelling. But the glioblastoma, like other types of malignancy is characterized by something we call a somanabolic uniqueness, as are other malignancies.
As you might have read in Dr. Seyfried’s new book, malignant cells tend to not be able to use ketones as a fuel source. And through what is called the Warburg effect, they tend to need carbohydrates to power themselves. I mean when you want to determine if a person’s cancer has metastasized, what do you order? You order a PET scan. But what is the PET scan? It’s an FDG fluorodeoxyglucose PET scan, and the malignancy attracts that glucose, concentrates the glucose because it needs it, and it lights up because it’s radioactive.
That said can we exploit this metabolic uniqueness of the glioblastoma, and look at targeting it by powering the body with pure fat, and not carbs? And in fact this was looked at, at least experimentally in an animal model, where these are the mouse glioma model assessment of gene expression of tumor growth in reactive oxygen species formation, and here’s what it looks like when you implant this glioma on Day 9 to 15. There you see it growing. It’s enhanced quite aggressively. But similarly in fact, the same graph, as we saw in the Lou Gehrig’s ALS model, significant survival in those laboratory animals, who were implanted with a malignant cell that requires glucose, but cannot thrive on ketones.
Look at the survival rate of those individuals who have implanted this glioma. These are laboratory animals, and this is, again, looking at cell growth versus standard diet versus a ketogenic diet. So there’s interesting information. The effect of the ketogenic diet on tumor growth is not simply due to reduction of available glucose, which it does. But may be due to some interactions with some gene signaling issues, and actually reestablishing the mitochondria’s ability to mediate apoptosis in the tumor cell. But nobody knows for sure.
In contrast to brain cells, these glioblastoma cells have not evolved to metabolize fat. So we’re trying to take advantage of the fact that they have this strong dependence on glucose that makes the tumor cells vulnerable to death, using therapies that target glucose metabolism. How do you target glucose metabolism? You take it away and you give a ketone fuel source. So this is an interesting report that looks at actually the metabolic management of glioblastoma giving a ketogenic diet, and again, this is Dr. Thomas Seyfried, who has a wonderful new book out. Been doing the talks shows, really fascinating stuff.
Here’s a woman who has…let me go back. She’s got memory loss, nausea, and headache for a month. It’s pretty aggressive, and you as you see here, a very, very aggressive contrast enhancing right frontotemporal malignancy biopsy proven to be a glioblastoma. So the enhancement with contrast medium is an indication of blood/brain barrier disruption, extravasation, and here we see the classic palisading of cells, the hyperchromic nuclei, and the irregularity of shape, poor differentiation, which is quite characteristic of glioblastoma. How was she treated? So she was treated with fasting, and again, fasting patients with cancer is brand new. This was just described in the Vedic texts.
This is exactly how malignancy was treated by fasting, and then beginning coconut oil. So how did that information get into that body of knowledge, 3000 years ago? It’s quite fascinating to think about that. Who discovered the longevity of consuming the bark of the gingko biloba tree? How does this stuff happen? But that’s, I guess, another discussion. So then she fasted and went on a ketogenic diet, and began standard therapy. Radiation, chemotherapy and surgical extirpation. This is looking at her blood sugar level, which tapers off, and we see blood sugar levels decline, as you would expect. But the spilling of the urinary ketones picks up dramatically and you would measure that on keto-sticks.
So we do ultimately reach a steady state of gluconeogenesis from protein in the diet, and in the body and ketone availability. Now watch closely. Watch what happens. Her MRI as we move forward with the treatment, really dramatic changes in this extremely aggressive type of tumor for which we really don’t have any treatment available. This is the FDG imaging for fluorodeoxyglucose. We’re imaging here for a sugar that’s been radioactively tagged, and the images in fact, reveal the area of decompression, but show no activity.
The conclusion’s actually quite interesting. The ketogenic diet got very well tolerated, obviously it would be and the response that she was predicted to have by standard therapy meaning radiation, and chemotherapy was unlikely explaining the results. Suggesting a therapeutic role for targeting energy metabolism, specifically of the tumor. The rest of the body thought being ketotic was very cool. The glioblastoma said, “Ah, where’s my fuel?”
Edema in this case, really quite interesting is suppressed without steroids, suggesting an anti-inflammatory of the ketogenic diet and calorie restriction. Well, we know that a ketogenic diet is powerfully anti-inflammatory because of its inhibitory role in what’s called NF kappa B signaling cascade initiator for inflammation. So this is really very interesting stuff. So I’ve now treated several patients with glioblastoma and we’re working with this mentality. Metabolic management of brain cancer, Dr. Seyfried then wrote this really powerful article that talks about this, is the study I presented. So I actually posted this on The Huffington Post, that when it comes to cancer we’ve got to look beyond killing things and disrupting, not only the blood/brain barrier, but powerfully damaging the microbiome.
Because of those downside effects, look at dietary interventions to treat cancer. So here we are. This is who we really want to be and this is how we want to power ourselves. A more ketogenic diet to upregulate mitochondrial biogenesis, that will ultimately reduce free radicals. So what regulates, what is it in your physiology that controls mitochondrial biogenesis? We know that the initiator of it, one of them is aerobic stress, aerobic activity and free radical-mediated stress. A ketogenic diet tends to enhance it, low carbohydrate. But what is it that these things are targeting? What is controlling the mitochondrial biogenesis?
And much work is focusing on AMP-activated protein kinase or AMPK. This is kind of the master metabolic gatekeeper, AMPK, and it mediates the uptake of glucose, beta-oxidation of fatty acids making these ketones available for utilization for fuel and AMPK is the gatekeeper turning on mitochondrial biogenesis. So obviously if it’s that important in terms of mitochondrial biogenesis, we need to know a lot about it. So AMP kinase is very sensitive to changes in the balance of ATP and AMP.
So when you’re consuming ATP quite readily when you’re exercising, for example, and ATP is being consumed, and converted back to AMP releasing the energy for you to utilize as ATP. That balance, those two things are sensed by AMP kinase, and it then goes to work to help you make more ATP. That’s the sensor. That’s the thermostat that says you need more availability of ATP. So if we have this balance then, normally in our physiology where we have this, let’s say balance of potential energy and kinetic energy possibly. This is availability. This is what’s been used, when that balance is tipped.
In other words, we have less ATP now because we’re creating more AMP because of our physical activities, moment-to-moment, nothing wrong with that. But there has to be a switch that can be turned that says, “Whoa. We are now under metabolic demand. We need to kick up the production of AMP.” So what signals the mitochondria to produce more ATP to harvest more fuel from our energy stores and to actually upregulate the growth of new mitochondria? And that is, of course, this AMP kinase.
I mention this energy store, as an interesting lead into the notion that most of us, if you’re an average American, will have about 2000 calories of stored carbohydrate glycogen, that’s available to us moment-to-moment. But we have about 40,000 calories available to us in our stored fat. I mean some people are walking around with quite a bit. They could power Los Angeles with their stored calories. But the point is you’ve got a full tank of fat available calories that you can burn at any given moment.
So we’ve had a lot of discussion during the breaks, about high-end athletes, what happens after about a half marathon, and again, there’s this idea of keto-adaptation. That you can be flex fuel and start to train your body to harvest its ability to utilize fat, as an energy source if you cut out the carbs. So here we go back, we need to turn on this system to produce more energy. So AMPK, not only does it conserve your ATP, but it’s simultaneously enhances generation of more ATP. It enhances glucose uptake, if glucose is available and enhances lipolysis. So right away understand that this system which is designed to give you energy during your activities, right away goes to work at breaking down your fat saying, “Oh, we’ve got all this energy stored. We’re going to start breaking down fat.”
It enhances protein synthesis. Enhances glycogen synthesis, trying to put the sugars away as glycogen enhances mitochondrial biogenesis. And as such, when there are more mitochondria to carry the aerobic load, then you have less free radicals produced and less oxidative stress. So we really want to pay close attention to what we can do to up-regulate AMP kinase because it really does some very good things in physiology. And there are drugs, actually, that work in this way. The uncoupling part of electron transport happens to a degree with metformin, and PPAR-gamma agonists, as well work in this way.
But again, it conserves ATP and enhances the production of ATP. So we’re going to plug the leak, and we’re going to fill up the tank with activation of AMP kinase. It enhances the growth of new mitochondria. You want that and as such is an antioxidant, and reduces oxidative stress. So you really want to know. You’re on the edge of your seats at 2:30 or 3:00 o’clock in the afternoon. What are we going to do here? Well, let’s take a closer look at AMP and talk about those factors that stimulate that up-regulated activity.
Caloric restriction, cutting back, and I am not talking about a draconian intervention. I’m talking about getting back to what normal people should eat in America today. The number of calories consumed by men is about 20% more than they need. In women it’s 25%. I’m talking about getting back to, not even a significant calorie restriction. But exercise is a dramatic up-regulator of AMP kinase, as you might expect, DHA lipoic acid and resveratrol. Now let’s get really excited. Because it turns out that the very balance of organisms in your gut, play a critical role in the activation of this gatekeeper, of this powerful switch controlling the destiny of your mitochondrial function.
We now understand that variations in the gut microbiota have a significant role to play in how we metabolize our fuel sources, and that is greatly influenced by the food choices that we make. And this is some very interesting research, where what they do is they actually take laboratory animals, and they virtually sterilize the gut, and follow various metabolic parameters. After they’ve reintroduced various types of inoculum that contain various types of bacteria, and can measure the effects on any number of parameters, based upon what was used to inoculate the gut.
Metabolic syndrome may be associated with profound microbial changes, and induction metabolic syndrome phenotype through fecal transplants, corroborates the important role of the microbiota in this disease. Dietary composition caloric intake appear swiftly regulated intestinal microbiota composition, and function, and we’re going to take this a little bit further. But your entire metabolism to some degree is influenced by the health of your microbiome. So the care and feeding of your intestinal bacteria is primarily important for whether you develop metabolic syndrome and full-blown diabetes or not.
And you’re going to be surprised to learn other things that can happen with respect to that. So you take this little guy and you sterilize, you purge the entire gut of all of it’s bacteria. Then you re-inoculate it with certain classes of bacteria, and lo and behold, this organism starts to gain weight. Something has changed its metabolism. And here’s what the article talks about that I think is really fascinating. Let me magnify this right here. Because it talks about how the microbiota, your microbiome plays a powerful role in regulating AMP kinase. That very same gatekeeper, really the master switch of your metabolism, is to some degree, well, significantly influenced by your microbiome.
You wonder when you see these kids in your practice who come in, who are overweight and suffering from issues with cognitive performance in school. Now you’ve got to start wondering, “Well, what’s going on with their microbiota?” And it’s not just because they’re becoming pre-diabetic because of the microbiome, but they’re actually eating foods to enhance that process. Now it is a really worrisome feed forward cycle. Again, look at all the cool things that AMP kinase regulates. These are all positive things for energy balance, a primary gatekeeper for energetics. So you really need to pay attention to it, and now we’ve just learned that a huge influence on AMP kinase is the actual microbiome.
How many of you are familiar with this study? Okay. So you’re kind of excited about it, like I am. I know one person knows about this because I discussed it with that person. But it’s really very exciting. I mean what a leverage point, now in terms of dealing with metabolic syndrome and diabetes. Think about it. Now I’m not saying that now if you’re a diabetic, you should stop somebody on the street who’s thin and ask them for a fecal transplant. That’s a little bit pushing it. But the point is the microbiome is adjusting the set point of your whole metabolism.
The microbiome, and what influences then, the microbiome, and therefore what influences AMP kinase? What influences your entire metabolism are things like how you were born, perinatal events. Were you breastfed? What are the foods you’re eating? What infectious agents have you been exposed to and what antibiotics have you been exposed to, as well? How much alcohol do you consume? What medications? Have you had radiation, and really important, what is the level of your hygiene? Now who wants to talk about the level of our hygiene?
We all have good hygiene, right? We wash our hands after we go to the bathroom. Our homes are spotless. I went to somebody’s house, and you could eat off the floor. So he really kept his house, really clean. No, I said it wasn’t clean. He had food all over his floor and you could eat it, but the point these are things we pay really close…well, we should pay close attention to, right? We should recognize that being born through caesarian section deprives that newborn of the initial inoculation, through the vaginal passage, which is fundamentally important for priming that immune system. Not only that immune system, but the immune system because it’s in great correlation with that of its mother and sets the stage for further priming of that immune system, based upon what that infant is going to receive through breastmilk.
That is deprived when caesarian section happens. It’s interesting to note that kids that have C-section births have a dramatic increased risk for ear infections and ADHD. Perinatal events, including being breastfed or not being breastfed. And I’m quite suspicious of the immunization protocols that children are receiving when they’re born, and they’re sitting in the nursery and they’re already hitting them with these immunizations. And then at age 12 months when they get 7 immunizations at a time. I’m concerned, not just about the preservatives, maybe that is a factor, maybe it’s not, but the profound insult that that might have on this developing immune system.
Food, food has a profound role to play in specifically regulating balances of all types of organisms in the gut. Infectious agents, for absolutely obvious reasons, anti- meaning against bio, meaning life, antibiotics and the powerful effects that antibiotics have on damaging the microbiome. You know I still get calls from friends at the office, “I can’t come in, but can you call me in a Z-Pak?” And I get those calls and I tell them, “No…” and they say, “Oh, do I have to come in?” “No, you’re just not getting a Z-Pak. You’ve got a viral infection for which you want an antibacterial. It makes no sense. Why do you want to do this to yourself?”
But if you go to a walk-in clinic, and you’ve got a cold, you will not walk out of that walk-in clinic without a prescription. If you did, you wouldn’t pay the guy, right, or girl? That’s what you expect, and now they probably add-on a Medrol dose pack, just for added damage to your microbiome. Think about it. If this is untrue, then you just let me know. But kids with ear infections don’t need antibiotics, by and large and when kids have sniffles, and sore throats, they’re not typically streptococcal pharyngitis anymore. But they’re getting bombarded, and there’s hell to pay with reference to the microbiome that ultimately leads to things, like metabolic syndrome, in my opinion.
But beyond that, as we’ve learned today when you disrupt the microbiome, there is hell to pay in terms of long-term immune set point reactivity. Dealing with things like auto-immunity and dare I say even malignancy and certainly inflammatory disorders, such as Alzheimer’s which is interesting for me. Alcohol, medications, radiation, and hygiene, we always want to make sure that we pay close attention, to making sure that we have great hygiene in this 21st century.
We want to wash our hands when our kids are out playing in the dirt. You’ve got to grab them by the collar because they don’t belong outside. And when your kid is next to another kid who’s got a cold, by all means, you better put a mask on both of them because hygiene is really important. This is a study that you may not have seen. You may not have seen it because it was published this morning, and actually I got this emailed to me after I had lunch. So I made the slide, as quickly as I could. It hasn’t actually even been published. It was forwarded to me, but you’ll see.
I’m not doing anything I shouldn’t. Hygiene and the World Distribution of Alzheimer’s Disease, here’s the subtitle, Epidemiological Evidence…this is so great…for a Relationship between Microbial Environment and Age-Adjusted Disease Burden. Wow, this is an incredible study. It came from Cambridge, and here’s what they found. They looked at countries around the world, in terms of their hygiene, as measured by parasitic load. How many parasites did they have? And they also looked at Alzheimer’s incidence, in the same prevalence of statistics…rather of Alzheimer’s, in these same countries, and they found these profound conclusions.
What I’m talking about is a so-called hygiene hypothesis. This is the hypothesis that says, “The cleaner we are the more in trouble we’re very likely going to be.” Because we’re not allowing bacteria on our skin, in our gut, to do what we’ve evolved to appreciate. The symbiosis is being compromised, and it’s very interesting. Because when you compromise the microbiome, as you’ve learned now over the past two days, it sets the stage for inflammation. So compromising the microbiome, being hygienically appropriate, using antibiotics, and sterilizing your hands at every opportunity ultimately leads to inflammation because the microbiome is compromised, a cornerstone of brain dysfunction, and specifically Alzheimer’s disease.
To get where I’m going, and that is that in Western countries the reason, one of the reasons…it’s not necessarily the turmeric that I showed you in India…but one of the reasons that we may be having such an explosion of things like autoimmune, inflammatory and other degenerative conditions has to do with the damage to our microbiome. That’s not a stretch, after these two days. You’ve gotten that message loud and clear. But this is the first study that I’ve seen that specifically relates it to Alzheimer’s disease. That our soaring rates of Alzheimer’s disease, yeah, I know they’re correlated to rate of diabetes increase, but may very well be related to the changes in our microbiome, and this isn’t even the coffee talking here.
This is just breathtaking stuff. So I actually did the best I could. It’s a tough slide and I usually don’t use slides like this, but it’s a slide looking at parasite stress. Who has the highest levels of parasites versus the lowest? These are the highest levels of parasite stress and we have Sudan, Ghana, Somalia, Senegal, Central African Republic, places like that, and these are areas that have very, very low parasite stress, the United States, Australia, look at Iceland. They don’t have a lot of parasites there.
Then here’s looking at the Alzheimer’s prevalence, and again, it is virtually identical. The levels of parasites are a powerful predictor of risk for Alzheimer’s disease. I actually went ahead and said, “What would it look like if we were able to superimpose these graphs?” And I did that and they line up pretty darn well. So what am I saying here? I’m saying that if we use parasite stress as a marker of what we would consider to be poor hygiene, it is a powerful indicator of reduced risk for this specific inflammatory condition. What else does the microbiome have to do with your brain? It’s an interesting report.
Consumption of fermented milk product with probiotic modulates brain activity and here’s what this study looked at. This was done, actually right here at UCLA. Healthy women are given either a fermented milk product with lots of probiotics…and I’ll show you what they are in a moment…a non-fermented milk product, basically milk, or a control. Now this fermented milk probiotic had five strains of…and here they are listed…and what was done was really quite interesting. All of the subjects in this study underwent functional MRI scanning, and they were given a brain response to emotional faces, attention task. How did they respond?
What was their overall stress level in response, to being presented images that might have been threatening or challenging to them, as measured by midbrain activity and other areas of the brain? So they did functional MRI scans on all three groups, and really unbelievable findings that with no interventions, the set point midbrain activity was high, but the milk reduced it. But a fermented probiotic actually had a powerful effect on brain activity as measured by functional MRI. A probiotic after its ingested is affecting an individual’s perception of the world. Is it threatening or is it not?
Probiotics can modulate the responsiveness of an extensive brain network in healthy women. Modulation of the gut flora can provide novel targets for the treatment of patients with abnormal pain, and stress responses. Now when we look at the incidence of depression, for example, in the United States, which is one in ten. And recognize that about 30,000 deaths each year are directly attributed to depression, and further recognize that according The Journal of the American Medical Association, women specifically taking the antidepressant medications have about a 42% increased risk for stroke, and a 35% increased of dying compared to women not taking those medications, this is a dietary intervention.
In my new book, I talk about simple, as we learn gluten sensitivity is anything but simple. But the role of gluten sensitivity in and of itself in terms of its relationship to depression. We’ve heard a lot of talk already about schizophrenia, and then this more specific gluten-related brain events, like gluten-related ataxia. But the gut flora are influencers of the set point of your emotional reactivity to the world around you. So why do you think so many of our kids today are so goofed up? And I would submit that we will learn soon enough, when the research is completed, that there is going to be this type of understanding, of the role of the microbiome will lead to other interesting ideas, as it relates to autism.
This huge inability to relate appropriately in a social way. I was asked by a Dr. Sydney Baker to write a chapter for his upcoming book about autism and he wanted me to think back about my first experiences with this disease, and the young woman’s name was Rebecca. While the mother and father were giving the history I was looking at Rebecca, and she seemed healthy enough, but had that autistic look about her and kept looking right over here, on my right side, and never made eye contact with me.
Until I remembered, thereafter I remembered reading research about how the fovea centralis is so importantly influenced by carotenoids, and their central vision may be a bit distorted. So that she was looking right at me with somewhat more of her peripheral vision. She was looking right at me the whole time. So I think this is going to prove to be very, very fascinating information. We then have learned a lot of things in the past couple of days that influence whether we’re going to have this brain that is highly functional and functioning or a brain that’s atrophic and profoundly dysfunctional. Let me show you.
We’re going to go through some case histories of patients, that I’ve seen. This is a patient H.D. and you might have heard his story. It’s actually been published. He actually spent some time on a wall, and you know about H.D., so this is published in The Journal of Nursery Rhyme Reviews. Anyway what happened to H.D. is he fell off the wall, and subsequently all the King’s horses and all the King’s men, could not put H.D. back together again. So while this is great. While the heroics are really quite wonderful, I think the mission really becomes to get H.D. off the wall in the first place. Because once we’re in this situation, we’re pretty darn ineffective. Yes, these are effective techniques for trauma and resuscitation.
But in the long run these powerful surgical interventions for our degenerative conditions really are not very effective at all, especially as they relate to the heart. But this is the mission. We’ve got to get H.D. off the wall. And because people do some things that aren’t real smart, I love this picture. It’s amazing what you can with an iPhone when people are not looking. But this is a setup for a disaster. This is H.D. on a different wall. I can’t take credit for it. I took it off the internet. But that said let’s get back to the fundamentals of the role of mitochondria, mitochondrial function, that ultimately leads to the death of the neuron. And look at this continuum, and these are now very well known factors that prove to be mitochondrial events.
Well, let’s look at what else can cause electron transport dysfunction. A wonderful report looking at the sera of patients with celiac disease, and neurological disorder evoke a mitochondrial dependent apoptosis. Well, that’s a bit redundant because apoptosis is always mitochondrial dependent, but that said, I don’t mean to be technical here. These are neuroblastomas exposed to sera of celiac patients, some with anti-neuronal antibodies, and neurologic disease, and some without, and here’s what was assessed.
Cytochrome c, which you remember is the transmembrane issue that ultimately targets caspase enzyme activation, leading to cell death. So we’re going to look at cytochrome c, caspase activation which initiates apoptosis, and then looking at mitochondrial respiratory chain activity. So let’s first look at the electron chain transport dysfunction in these patients, with all kinds of interesting neurologic problems that have obviously nothing to do with celiac disease or gluten sensitivity, as it were. I mean what in the world would multiple sclerosis have to do with the gut?
I’m going to show you an interesting article that reveals that there’s a couple of articles that deal with the possible relationship of MS and the gut. Cerebella ataxia, we’ve talked about in epilepsy and so these are patients who have neurologic issues and we’re looking at control sera, neurological disease without neuronal antibodies, and finally neurologic disease with neuronal antibodies. Assessing complex 1 mitochondrial respiratory chain activity. So right off the bat, you see that folks that have neuronal antibodies, and manifestation of neurologic disease, have acquired, or may have inherited a complex 1 mitochondriopathy.
Now what we’ve learned is celiac disease is something you may not have at birth, and likely don’t have at birth. You might have this predisposition, based upon your heritage, but even if somebody were to take the diving board off of your gene pool, you still can get celiac disease. So late in life, what happens? It’s kind of another story. Now let’s take a look at caspase activation, which leads to cell death. What happens with caspase? We can actually stain for caspase-3 in the control versus those with anti-neuronal antibodies and neurologic disease.
So we’re staining for the enzyme that induces neuronal death, and again these are in patients with celiac. They don’t have a primary neurologic problem yet, and let’s look at neuronal death. How do we assess that? Using TUNEL, which is terminal deoxynucleotidyl transferase. When DNA fragments, this is the way you can stain for fragmented DNA, a marker of apoptosis. When your cells die, your DNA will fragment, and you can actually stain for that, as you see here. This is a marker of cells that have undergone apoptosis. And as such, a dramatic increase in neuronal apoptosis in these patients with neurologic disease and anti-neuronal types of antibodies.
So these anti-neuronal antibodies in celiac patients evoked cell death. When examining celiac disease without neurologic disorders, and anti-neuronal antibodies, a certain degree of apoptosis, although to a lower extent is happening. And what is so important is the pro-apoptotic mechanism is likely dependent on the combination of anti-gliadin and anti-tissue transglutaminase antibodies, which we see a lot of. I mean if you start testing you see that a lot and well, why would tissue transglutaminase antibodies have anything to do with the brain?
What you want to do is understand, well, if you have an antibody against transglutaminase what does tissue transglutaminase do in terms of transglutaminase? In terms of protein synthesis and maintenance? And when you compromise that enzyme you have to think of the implications in terms of protein adequacy in certain tissues. So again, we need to understand that there are some powerful things now lurking in the environment that ultimately lead to mitochondrial dysfunction. So this gluten stuff, that you’re hearing about, is something to think about as directly related to mitochondrial issues, and specifically the brain.
Well, how in the world does that happen? How do you get from the gut all the way up to the brain? How does that work? I just don’t know. We’re going to have to explore that. Lots of things, as a consequence of being sensitive to gluten sensitivity. So yes, it’s all interesting to look at the changes in the microvilli. That’s important when you deal with celiac disease, certainly. Just ask a gastroenterologist, they’ll tell you whether you do or don’t need to be gluten-free based upon this histology. But I would also indicate to you that this is a consequence of being gluten sensitive, published in The Journal Archives of Neurology and I’d like you to take a look.
So if you were give this to a neuro-radiologist, blindly. I think blindly you’d be going around, you’d never find him or her. But I would think that the read on this would probably be without clinical, you’d probably say demyelinating disease, or secondarily you might say ischemic vascular encephalopathy. But there’s a lot of white matter change, especially in the periventricular area where there’s a lot of transmembrane kind of transfer of things. Serum and Gluten-Related Disorders Consensus on New Nomenclature and Classification, I guess I heard yesterday that we’re going to get new one of these pretty soon.
I’m hopeful. So again, this is work by our very own Dr. Fasano, and we saw this, and I think it’s a very interesting graph, looking at the gluten-free diet. And basically it’s a Google marker and another statistic you can look at is the sale of gluten-free foods, gluten-free this, and that which is also skyrocketing. But I would warn you that a lot of people who go gluten-free, who don’t then buy the gluten-free foods. I mean who are getting the message that it’s not just gluten-free, but low carb is also. I mean there are gluten-free breads and gluten-free pastas, and probably gluten-free gluten, from all I know. But the point is a lot of people are saying, “Well, I’m just going to stop eating those gluten containing foods, and not worry about the gluten-free things that are now aisles in the grocery containing.”
So gluten-free products are now $2.5 billion. That’s as of 2010. I guess I’ll update that soon. But what is gluten? I didn’t incorporate it. I was asked to do this on a video and I have a blooper roll. I couldn’t get it right. I had the gluten. I put the flour…and the blooper roll is funny. But it’s a bit embarrassing because I couldn’t get it right. But anyhow what is gluten? Well, I was asked that question after a recent conference, and I decided on my way home at the airport to film the guy that makes the pretzels. Because gluten is this sticky stuff that allows him to cut the dough and measure it out, and watch this. You could not do this if it wasn’t for gluten.
So this is why we have wonderful gluten. Because if it wasn’t for gluten, we wouldn’t have these pretzels. So therefore we should stop worrying about gluten because you can’t tell the world to stop eating these pretzels. Look at how sticky it is. This guy thought I was weird. I think he thought I was a stalker. There they are. Look at how wonderful that is. So if there wasn’t gluten in our society aside from gluten, and all the other proteins that you’ve heard about, we wouldn’t have this. So what Dr. Fasano’s team determined was that this wheat allergy is an Ige-histamine type allergy. It may have some relationship to people who have events related to that.
This celiac disease with tissue transglutaminase and anti-endomysial antibodies, involving the gut mucosa, but also these markers being involved, in things like gluten ataxia and dermatitis herpetiformis. So again, right off the bat, even according to their nomenclature, celiac disease, even with this finding alone, is not exclusively a small intestinal issue. I had the experience recently of having one of my patients who had chronic migraine headaches. I put her on a gluten-free diet and for the first time in a couple of decades, her headaches when away. It’s not an uncommon event. She saw her gastroenterologist who planned to do an upper endoscopy on her.
Does so, finds that her jejunal biopsy is totally fine and says, “There is no reason in the world that you have to be on a gluten-free diet,” and she phoned asking me, “Why in the heck did you do that?” And I didn’t have the words. I mean I didn’t have the words. You know if you can’t say something nice…and I’m not trying to be critical of him. It’s often said, “Don’t criticize another man, until you’ve walked a mile in his shoes.” You know why people say that? They say that because then when you do criticize him, you’re already a mile away and you have his shoes.
But anyhow I think it’s better to light the single candle than to curse the darkness. But sometimes you have to curse the darkness a little bit. Then finally this gluten sensitivity is it the innate immune system? Well, I have to tell you, the more I review the literature, and I attend these lectures so that you’re feeling comfortable, I’m a bit confused. I am perhaps more confused. There are a lot of Apple computers in here. I’m more confused. It used to be pretty easy. It used to be, either you had celiac or maybe you had this new thing, gluten sensitivity. You wouldn’t really see much wheat allergy. But it was easier. Because now I don’t really know.
Are we talking toll-like receptors? Are we talking about macrophages? What part of the immune system is involved here, and as we clearly see, aside from the markers of the tissue transglutaminase anti-endomysial antibodies, anti-gliadin antibody. When you take a step back, and look at these patients clinically, people are sensitive to gluten in many ways. Whether it is what we have, called celiac or what the people call celiac. I’m celiac. I love that. What does it mean? Or is it gluten sensitivity or what? I mean I’m ultimately thinking this is a what we should call it. There’s more of a dysbiosis, which seems to be the harbinger to this, in most people.
But leave that as it is, let’s look at gluten sensitivity and this is really important. That gluten sensitivity may resemble symptoms of celiac, but the presence of extra intestinal symptoms, who knew? Behavioral changes, bone or joint pain, muscles cramps, and so let’s look at these behavioral changes when a person is gluten sensitive. You can pave the way for gluten sensitivity by affecting the microbiome. Can you? We see this when people get acquired gluten sensitivity. When you bombard people with powerful antibiotics, you’re setting the stage for gluten sensitivity and other types of sensitivity, as well.
And believe it not, there are some antibiotics being used today that not only do this, but in and of themselves, are direct mitochondrial toxins, beyond this entire mechanism, and those are the fluoroquinolones. So this notion of fluoroquinolone toxicity being a mitochondrial event is very real. But this is what the group came up with in terms of gluten sensitivity. All of these extra intestinal events, foggy mind, fatigue, depression, and again, we just learned that a probiotic can affect your perception of the world and your mood affecting the microbiome. It’s becoming really interesting and I tell you I am more puzzled by it every day.
Because when you think you finally have it…so don’t feel bad…you think you finally get this, it just gets perplexing, and as we’ve seen this, so normally 30%. But in gluten sensitivity we see a higher representation of the human lymphocyte antigen predisposition. So Dr. published this report talking about non-celiac gluten sensitivity and how it overlaps with Crohn’s disease. But really I want to just say that a gluten-free diet is what is recommended for those who meet the criteria of celiac disease. Unfortunately that leaves out many non-celiac gluten sensitive people, suffering unnecessarily from very serious symptoms.
So let’s take a look. Let’s look at this young man. This is K.L. He’s 23 years old, and he has a 6-month history of having developed abnormal movements. He’s got a movement disorder. He was seen by a movement disorder specialist team and was told that he had some form of either essential tremor or dystonia, or possibly myoclonus. When you go to a neurologist, you’ll get a name for whatever you have, and that’s pretty much what you’re going to get. Now the more complicated sounding, the more you think you got your money’s worth.
So if you walk out of there with post-infectious ascending polyradiculoneuropathy then you better pay that guy a lot of money. The question is, “Great, let’s not worry about what we call it.” I usually tell people, “Look, I don’t really know what you have…” and I use their last name, “…you’ve got…” whatever his last name is, “…syndrome.” They say, “What’s that?” I say, “That means that’s what you have because that’s your name.” I am very serious about that. I am not so vested in naming the illness because it doesn’t help me at all. Because it doesn’t pave the way to a specific page on the cookbook for what I can do. That cookbook doesn’t exist.
So what is he offered to treat his movement disorder, Inderal, a beta-blocker or Botox-ing his arms and legs? But interestingly enough, when you dig a little deeper, he has frequent bowel movements, fatigue, poor sleep, and as a kid he had a learning disability in the fourth grade and poor attention. He had ADHD as a kid, but he wasn’t treated as if that’s treatment. He wasn’t going to receive amphetamines. Yes, that’s what we do. So let’s take a look at this young man and you’re how old?
My oldest son.
Can you hold your hands out in front like that? Okay, so what did we do? We screened him for Huntington’s. You get young man with a movement disorder like that, you’ve got to be sure it’s not Huntington’s, Wilson’s disease, check ceruloplasmin, excretion of copper in the urine, and with the bowel issues, the learning disability we did anti-gliadin and antibody. Who knew? Which oddly enough, came out positive, so what did we do for this man with a movement disorder? We put him on a gluten-free diet, and actually I didn’t see him again. This is nine-months later. His mom videotaped him and sent me the videotape. This is actually a video. He’s sitting there.
So we’re having him walk around and hop over there, and again, I just wanted to let you see his gait is well. He’s rushing off to work, but do you want to say anything, Keith?
Hello, Dr. Perlmutter.
We want to say thanks to you for everything that you’ve done.
So thank you. It’s an interesting time in my life when these things happen. Because people say, “Well, this is outside of the box and is that where you want to be? Do you want to be outside of the box? Is that your mission to do outside of the box?” No, the mission is to make the box bigger. So that people with these issues, we raise our level of suspicion and we treat them effectively. I also looking at this video, I think mom’s got a movement disorder. Do you see that camera? I’m going to have to talk to her. I think she’s got an essential tremor. We need to Botox her a few times. Well, as fate would have it. This is a true story. He lied. They went to see their neurologist afterwards, and the mother brought along a little camera, and videotapes their encounter with the doctor.
Hello, Michael. How is the tremor? Are you taking the medication I prescribed for you?
My tremor has disappeared completely and I never took the medication.
Well, I guess you must have had the Botox injections.
No, I didn’t have the injections. I went to functional medicine practitioner and he put me on a gluten-free diet.
That makes absolutely no sense. You do not have celiac disease.
You are absolutely correct, but I am gluten sensitive and now I’m free of the tremor.
Heck, yeah. That’s on YouTube. I think it’s called Michael’s Tremor. But anyway I wrote that for Huffington Post. Gluten-free is becoming kind of a moniker. It’s now being exploited left, right, and center because something magical happens if you eat gluten-free. We now see this is Dunkin’ Donuts offers gluten-free donuts and muffins. That’s like low-tar cigarettes or something like that. This is breathtaking and that’s going to attract people. “Well, I am celiac, so I can go to Dunkin’ Donuts and pound these donuts and be just fine.”
Well, that said the question really becomes what should you have for breakfast. Well, I think steel cut oats, for example, a wonderful choice in this gluten sensitive world, right? We want to pack in that oatmeal anyway that we can or should we? This is a study that was published in The New England Journal of Medicine and they evaluated the gluten levels in some popular brands of oatmeal. Actually they did this ELISA study of three brands of oatmeal, and keep in mind that the certification of a gluten-free food is one that has less than or equal to 20 parts per million.
They had three different types. They had stuff that was supposedly milled in an oats only facility. Country Choice which is obviously a great choice because it’s organic and then good Old-Fashioned Quaker Oats. I mean I’ve already bashed OJ, orange juice, not OJ. Sorry. I better look around. Actually no, I’m in L.A. I’m near Brentwood, anyway. So and Quaker Oats, everybody grows up with Quaker Oatmeal. We used to keep the container for all kinds of things.
But that said let’s look at what happens in terms of the gluten content from The New England Journal of Medicine. This is ten years, looking at gluten-free oatmeal, with 20 as our cutoff, half of theirs exceeded it, and one dramatically exceeded it. Organic, 75% of it dramatically exceeds the cutoff for being gluten-free, and of course, oatmeal from Quaker Oats. This is a lot of gluten. So I would object to oatmeal based on its glycemic index alone. But we really have to look at things, like contamination in factories and claims. So 75% of these samples were actually not gluten free.
Occult celiac disease, presenting as epilepsy and MRI changes that go along with that, so this is really quite interesting. Looking at a 30-year-old man. Do you like the little bullet points here? I worked on that diligently. Has a two-year history of headaches and refractory seizures. What do they do? They biopsy his brain, but look he’s got a rash. He’s got chronic constipation. That’s not just part of the history that you don’t pay attention to. People say, “What do you do?” and I say, “Well, I’m a gastro-neuro-endocrinal-functional psycho, yeah. That’s me.” But you’ve got to look at everything from anus to ulna, in my opinion. So that said we don’t write this stuff off.
And look at him; he’s positive for tissue transglutaminase anti-endomysial antibodies. He’s goes on a gluten-free diet. He becomes seizure free for two years. His antibodies normalize and incredibly his contrast-enhancing lesions, contrast-enhancing lesions disappear. Why on earth would contrast-enhancing white matter lesions in the brain disappear going on a gluten-free diet? I mean you’d look at that and say, “This fellow has multiple sclerosis.” That connection is actually very new. The idea that white matter lesions can be related to the gut.
That’s really quite a stretch. But I show you this because this is a study from The Journal of Neurology that looks at how we should be treating epilepsy patients, and here’s what it shows us. The temporal lobectomy’s continue to be underutilized, damn it, as a treatment for epilepsy. Patients who are medically refractory after failing just two drugs, you get two shots. After two shots and you fail, we’re going to whack out your temporal lobe. “Patients who fail two drugs should be referred to a comprehensive program of regular professional care.”
That comes from the back of “Crest has been shown to be an effective decay-preventative dentifrice that can be of significant value when used in a comprehensively applied program of regular professional care.” That’s on the back of Crest toothpaste. I was reading it this morning. Ah, sorry, anyhow. But that’s what their telling us. “If you fail, if your Keppra and Lamictol aren’t going to cut it, we’re going to whack out your temporal lobe. That’s what we’re going to do. That’s the treatment for you.” I just love it.
But Dr. Hadjivassiliou has really made us quite aware that there’s a lot going on between the gut and the brain. Most patients who have these neurological manifestations of gluten sensitivity have N-O gastrointestinal symptoms. So you have to have a higher level of suspicion. Talk about the rash. Talk about their history. Talk about their birth. Ask them if they were breastfed. People think that’s a strange question. I ask that question of every multiple sclerosis patient, “Were you breastfed?” And I don’t ask it when they walk in the room as a first question. They kind of would turn around and walk away. But I work it into the conversation somehow.
Patients with celiac disease might not have gastrointestinal symptoms, either. Therefore gluten sensitivity cannot be diagnosed on the clinical basis alone. The take home message from this conference is high index of suspicion. What else? Most patients who present with neurologic manifestations of gluten sensitivity have no GI symptoms. That’s kind of watchword for me. I have that emblazoned in my office when you walk in. Not really, but I should.
But this is what he has talked about, in terms of neurologic issues, peripheral neuropathy, encephalopathy, being confused. Being cognitively impaired. Myopathy, like we sometimes see with statin drugs. Myelopathy, spinal cord issues, Stiff Man Syndrome which is now called Stiff Person Syndrome. Glutamic acid decarboxylase related. Chorea, movement disorders. Think about that, Mr. K.L. Movement disorder responsive to gluten restriction. So movement disorders can be a consequence of gluten sensitivity and epilepsy, even epilepsy.
Why not put people on a gluten-free diet, before they have their temporal lobe excised? I’m just saying. Headache and white matter abnormalities. Again, Dr. Hadjivassiliou associated the gluten sensitivity. He showed that ten patients with gluten sensitivity they have…these are not classic descriptions of tissue transglutaminase, biopsy-proven celiac disease. They have headaches. They are unsteady. So it’s more than a headache. They’re neurologically compromised, and four of them have ataxia. They have demonstrated uncoordinated movements.
Look at these white matter changes from gluten sensitivity alone. Holy Toledo, what’s going on in the brain of people who are consuming gluten, who may be sensitive to this? This is huge. Nine of ten, experienced resolution of symptoms by going gluten-free. This banker came to see me, 30 years of suffering headaches. On narcotics, every day Vicodin and Imitrex, every single day. A triptan drug, and then how do you get off of a triptan drug if you’re taking it every day?
No benefit from beta-blockers, calcium channel blockers, and now these days, Topamax and trying to prevent the headaches. So you talk to this guy. His exams are normal, but he’s got a 20-year history of stiffness in his muscles and his sister has the same thing. So to me, I’m thinking about Stiff Person Syndrome, which is anti-GAD65 related. That’s a gluten related antibody and has a family history of positive stiffness in his sister. So his examinations are normal and we test him. We look at his lab studies. These are the out-of-range. He lights up and sure his GAD65 IgA is positive. But look at his antibody findings. We put him on a gluten-free diet.
He was also sensitive to dairy. We took him of dairy. He’s now having two to three headaches a month. His worst headache is five out of ten. No Vicodin, no more Imitrex, his muscle stiffness has resolved. This is 30 years later. Now they’re…I’m probably going to think about whacking out his temporal lobe these days. And watch what happens to his markers, after going gluten-free, so a pretty aggressive change there. We actually published his case because it was so fascinating. Here’s, again, as I indicated earlier really a pillar of one of those life changing articles that really sets the stage. It really humbles you and sets the stage for you to be more diligent in your work and looking at things in a different way.
Zonulin and it’s a regulation intestinal barrier function, the biological door. Intestinal barrier function, the biological door to inflammation, autoimmune, and cancer. I mean if you’re talking inflammation, and autoimmunity and cancer, there’s not much left when you think about it. And here’s how it works. The consumption of gluten containing foods liberates a gliadin, which binds to a receptor, and then stimulates intracellular release of zonulin that binds to its receptor, which then causes disassembly of this tight junction. So everybody got that?
That was pretty straightforward. When the mooring lines are disrupted, the boats tend to drift apart, and therein is a mechanism that has implications, beyond anything I can express. Because once that happens, gliadin and other proteins get in where they don’t belong. They permeate what was thought to be this impermeable barrier. There was thought to be, as Dr. Fasano said, “Grouting here that didn’t allow anything to pass” which doesn’t make sense because things go both ways, and always have, just because we didn’t discover it.
And these proteins are stimulating macrophages, and T-cells, and doing all kinds of things that are not good for our immune system. And as Dr. Fasano said, “This is a proven relationship.” As he showed us this morning, possible relationship, I think very likely relationship with multiple sclerosis, and that’s kind of a new thought, starring…there’s a great word there…roles for the astroglia in barrier pathologies of gut and brain. So starring because it’s the astroglia…that’s the play on words. You have to get that stuff.
These authors try to sneak this stuff into you people who are really reading them, critically. And what it’s telling us really is that the gastrointestinal tract is, as you would expect, highly innervated. Large populations of these astrocyte-like glial cells line the intestinal mucosa, and receive signaling information from the intestinal mucosa, what is now considered this enteric neuropathy plays a central role in chronic gastrointestinal disorders Well, we know there’s got to be some nerve involvement. If you get diarrhea, you get cramping, which is a nerve to muscle, and you get pain.
So that right off the bat, tells you that there’s nerve involvement, but it’s much deeper than that, much more intense. Because this, taken from the study looks at permeability issues, and the permeability is governed again by the junction, the tight junctions between these epithelial cells, the intestinal epithelial cells. But also very important then is the role played, by this enteric glial cell, in sensing this permeability issue, and subsequently producing various proteins that have an effect on the rest of the body. Yeah, they have an effect, locally.
But these same proteins govern activity and functionality of other astroglial cells that are in the brain, and can right away lead to similar issues, as hyper-permeability here, as in the so-called inviolable, inviolate blood/brain barrier. So what a connection then between leaky gut syndrome and what we would call then leaky brain syndrome. I mean it’s bad enough having a leaky gut. It’s bad enough that for years, we who talked about leaky gut were told that we had a screw loose somewhere. I won’t deny that I have a screw loose somewhere. That’s fine with me.
I do deny the part about losing some of your marbles. I want my marbles. But nonetheless, these findings provide evidence that these glial projections, in both brain and gut, contribute interchangeably to barrier functions. Barrier function in the gut, barrier function in the brain, suggesting an unrecognized paradigm, whereby cellular interactions previously thought to be unique to the blood/brain barrier also regulate gut epithelial permeability and vice versa. That gut permeability issues crosstalk with the central nervous system, and have an effect on brain permeability. Again, it’s one thing to have a leaky gut, and I’m not knocking it.
But a leaky brain is something to be concerned about, as well. These cells secrete several mediators that implicate blood/brain barrier formation and function. Disruption of the blood/brain barrier plays a fundamental role in neuro-inflammatory disorders. So where we are now is this understanding that there’s this relationship between the gut and the brain that focuses on permeability of the gut, and factors that regulate brain permeability. Who knew? So this is the blood/brain barrier and these are the astrocytes, and when these astrocytes are affected by the gut they change the relationship of their function to the brain, and lead to hyper-permeable blood/brain barrier.
Dr. Fasano studied zonulin levels in patients with multiple sclerosis, of all crazy things, and this was recently published. Showing that in control patients, here’s their zonulin levels. Secondary progressive patients have a huge uptick in their zonulin levels. It relates to blood/brain barrier permeability. Relapsing, remitting MS, whacko levels of zonulin. But when they go into remission their zonulin levels come down. That’s really important, so you’ve got to understand that the zonulin gluten/gliadin/zonulin connection in the gut, as it relates to gut permeability extends to the brain. Blood/brain barrier penetration of solutes.
So that then when we see Dr. Hadjivassiliou’s MRI scans, showing these issues in people who have gluten sensitivity, I’m now going to interpret this as a representation of a leaky brain syndrome, and an inflammatory response initiated in the brain, by something happening in the gut. This is some new information showing that, in patients with multiple sclerosis, lactobacillus counts could hardly be measured, and what’s called the dysbiosis index…that’s a measurement of bad versus good bacteria…is dramatically elevated. Normal should be 0 to 3.
And this is interesting because it talks about white matter, hyper-intense focal white matter lesions seen in 20 of 48 patients with Crohn’s disease, an inflammatory condition of bowel. And what is interesting is I published this 20 years ago. It’s back to haunt me, anyway. Let’s take a look at some cases. So this young woman has had a variety of symptoms. She has night sweats, abdominal cramping, bloating after eating, carbohydrate craving. What do those suggest right off the bat? So SIBO. Did I hear SIBO, yes. So SIBO or perhaps even Candidiasis. And poor concentration, as you would expect, she’s got an inflammatory issue of the gut and she cannot concentrate. She was probably hit with antibiotics, as a kid.
But she also has OCD and she’s depressed. You now have a new frame of reference for looking at a patient like this. At the time I saw her this was several years ago, I didn’t have this complete frame of reference. But you can predict that she would have had a lot of infections as a child, and got lots of antibiotics. So she had traumatized her microbiome, setting the stage for what’s to come. She was not breastfed, lots of antibiotics, and now endometriosis with a proven ovarian mass. Look at her IgG and IgA to gliadin, and I tested her for candida antibodies which were somewhat elevated. Gluten-free diet and some fluconazole, 100 milligrams for 21 days.
At one month her night sweats and abdominal cramping, virtually everything has resolved, even her OCD and her depression, by treating her with a gluten-free diet and in this case, I don’t know what the effect was of the candida. But I strongly suspected candida overgrowth in light of her antibiotic exposure. This is a 33-year-old woman who’s chief complaint is a 3-year history of jerking of her arms, poor sleep, anxiety, so really nothing GI-related. Yet, when you talk to her about her past history though, her ANA is high, and what have we now learned about autoimmunity? That’s a pretty darn high ANA and you add some thyroid antibodies being positive, and this is a woman whose autoimmune is lighting up like a Christmas tree.
MRF of brain is negative, surprisingly in retrospect. Her DYT alleles 1 and 2, those are inherited forms of dystonia, genetic markers that, I guess as a neurologist you’re supposed to check. I did. I probably couldn’t be doing that anymore. Why? I’m going to change her genome. Do some gene surgery on her. But her gliadin markers are elevated. What did we do for her? She goes on a gluten-free diet, and then has some 90% improvement of her dystonia, and her sleep problems and anxiety have resolved in one month.
This is coming from the group in Houston, Dr. Joseph Jankovic, now looking at movement disorders and autoimmune disease and Sydenham’s chorea, and this PANDAS, pediatric autoimmune neuropsychiatric disorders associated with streptococcus 2. Ideas that streptococcal infection, may through the mechanism of molecular mimicry may attack certain parts of the brain, and lead to movement disorders. But what about lupus movement disorders? As we just saw that woman had a high ANA. Gluten sensitivity they actually discussed, believe it or not, perineoplasty and autoimmune encephalopathies.
And here’s a case of TR. I better hurry. She has a three-year history of progressive twitching of her left face, and she’s been diagnosed with hemi-facial spasm. Her treatment was offered to her. Botox, her entire left side of her, probably about every three months. If you go to neurology school that’s what you’re told. This is in the book. This is how you treat hemi-facial spasm. The other opportunity here is to do a posterior fossa decompressive craniectomy. And isolate the anterior inferior cerebella artery or AICA, which is called the Jannetta Procedure developed by Dr. Peter Jannetta at the University of Pittsburgh.
And you put a piece of gel foam because he thought that there was a lupavica artery that pushed against the facial nerve, and that’s the other option. She in fact was offered this as an option to treat her hemi-facial spasms. She has a history of migraine headaches, hypothyroidism, and iron deficiency. There’s something going on in her gut. Can you imagine? Asking a patient with hemi-facial spasm about the rest of her history. So you look at her MRI and she’s got multiple white matter lesions, to the extent of the report said, “Possible multiple sclerosis.”
What did we just see, with Dr. Hadjivassiliou’s case reports? Dramatic white matter lesions related to gluten sensitivity in the patients that happened to have headaches, and let’s take a look at her.
This is how my face looks when it’s spasming. When I’m trying to talk, it’s worse when I try to talk. It’s worse when I’m nervous or stressed or someone looks at me. If I just relax all my muscles, and don’t move anything, I can control it a little bit better. If I put my lips together, it automatically does it. And if I smile, my smile is very crooked. But basically just generally talking, my face spasms, pretty strongly a lot of the time.
Don’t you feel that in your heart for her? Why in the world did we study her in this way? Well, there are a lot of reasons, not the least of which was her anemia, the iron deficiency. The understanding the gluten sensitivity can cause movement disorders as we now know. So what did we do for her? I gave her some glutamine, Vitamin D and a gluten-free diet, and put her on some probiotics. At 32 days I get an email. She has almost complete resolution of symptoms, stating, “I can drive again.” I asked her to email me a video clip of her. I got it two days ago. I actually did this on the plane, incorporated it. And as you can see, gluten-free makes your hair go curly.
Hi, this is Terri Rigby and I’m making this video to show the difference in my face since having gone gluten-free. It’s been about four months now and the spasms are almost completely gone. I’m driving again. I have my life and I’m just so thankful for all the learned going down to Naples, to see Dr. Perlmutter, and learning just how much diet affects the brain. And I just look forward to continued progress and I’m just very, very thankful for everything.
Again, what did Dr. Hadjivassiliou say? He said that most patients who present with neurological manifestations of gluten sensitivity have no gastrointestinal symptoms. You’ve got to think about this stuff. And this is you now. You are the prepared mind that Louis Pasteur talked about. Chance favors the prepared mind. Now you’ve got these tools.
I didn’t give you a cookbook about how my alpha lipoic acid or what’s the dosage of intravenous glutathione. What we’ve tried to in this symposium is just raise your index of suspicion. That’s the most powerful tool, and realize how pervasive this issue with gluten sensitivity really is, and listen to our patients. This is a man who says, “Look, Doctor, I have this suspicious looking mole on my shoulder,” and when you look at it, “You’re darn right that things suspicious.” So I will tell you, I can’t begin to tell you how grateful I am that you’re interested and have given me this time to be with you. It honors me to my depth that it’s important to you. Thank you very much.