Autoimmune Revolution Summit 2017
Dr. David Perlmutter MD Board Certified Neurologist
web page drperlmutter.com
My Notes from an Interview with Dr. Perlmutter
Brain Inflammation, Autoimmune Disease and Nutrition
A couple of decades ago, in terms of neurology, I found a lack of satisfaction and we were being very myopic in the way we were dealing with our patients and dealing with their problems. We were just focusing on the symptoms as opposed to really taking a step back and identifying, and then treating the actual causes of the problems, that we were seeing day in and day out. In neurology as well as other areas of medicine, by and large, the mechanisms that are involved in causing the body to deteriorate involve two issues. Number one inflammation and number two the action of chemicals we call free radicals, or free radical mediated stress. Taking a broader view of those processes I began to wonder what causes those issues to occur in the body. I began to identify certain lifestyle issues were playing fundamental roles in ramping up inflammation, we learned that dietary issues really played a role in increasing inflammation. It was about that time that there began to be some suspicion that perhaps there was a relationship between elevated blood sugar which was really coming on the scene at that point.
It was around 25 years ago when we were told to stop eating fat, what happened of course is people started eating more carbohydrates, eating a lot of grains and blood sugar started to climb. The rates of diabetes skyrocketed in America and along with that were things like coronary heart disease and even Alzheimer’s. In recognizing that Alzheimer’s is an inflammatory condition, and higher blood sugar is related to inflammation, those were two very important dots that were then connected in my mind. So I began looking at lifestyle issues and how they relate to risk for neurodegenerative conditions, not just giving people pills to treat symptoms, but rather on how we focus on the fire not just the smoke. It was at that point that I really realized that our nutritional choices are probably among the most important choices that we make day-to-day in terms of our momentary health. Also certainly in terms of our long term health, or lack there of, for developing a condition like Alzheimer’s for which there is no cure. When you phrase it like that, recognizing that our lifestyle choices influence risk for situations that have no remedy, then it really adds a layer of importance to looking at that sort of information. Low and behold a couple of decades ago there were plenty of publications talking about things like blood sugar, diet, and even things like gluten sensitivity. And how the issues could relate to ramping up the inflammation and therefore in my mind how that could relate to the field of neurology.
The results even to this day that are achieved simply by looking at problems and trying to find symptomatic solutions, at least in the field of neurology, remain pretty much primitive. It remains a field of diagnose and we have no effective treatment, and certainly no effective cure for Alzheimer’s disease as we have this conversation. There is nothing that is available from a pharmacy that has any meaningful effect on slowing the progression of that devastating situation that is effecting more than 5.4 million Americans and costing us 200 billion dollars a year. Globally there are more than 46 million individuals that have been given this diagnosis and we expect that the rates of Alzheimer’s will triple by the year 2030 and that’s just around the corner. An even more sobering way of looking at this we’re seeing Alzheimer’s developing in people younger and younger. The notion is this is what happens when your brain gets old is interesting, as your antioxidant defenses begin to fail. But now we’re seeing it in people in their 40s and 50s just like the shift that occurred in what we used to call adult onset Diabetes, we don’t call it that anymore because we see it in teenagers.
There is no question that this is not a genetic change, it’s not that our genes have suddenly changed but it’s an epigenetic change outside of the genes that’s affecting their expression, and that means the good news. What’s referenced in that paradigm shift is that it offers up opportunity to make positive changes and reverse the trend. I think that’s what my work has become focused on, gaining the publics interest in the fact that they can determine their health destiny as it relates to so many problems that are becoming so common in cosmopolitan societies, like autoimmune conditions for example. You may ask how are autoimmune conditions related to the brain? Why would I be interested in an autoimmune condition? Well it turns out that Graves Disease Autoimmune Thyroiditis is a problem well beyond the thyroid, the entire body is involved. In fact pretty much any autoimmune condition that you might talk about whether it is Hashimoto’s Thyroiditis, Sjogren’s Syndrome, Lupus, Rheumatoid Arthritis, Diabetes Type 1, Celiac Disease, you name it. The whole body is involved and indeed when the whole body is inflamed the brain is involved in that as well.
When we see people who have autoimmune related bowel conditions the brain is involved in more than 50% of the people in terms of their symptoms. Even in terms of their mood we know that with even Dermatomyositis, this is a skin and muscle condition that people have cognitive issues, as well as they do have with Lupus and other autoimmune conditions. We tend to relegate the autoimmune conditions to a particular organ system and in reality we have to take a step back. We have to recognize that when the immune system has gone awry the entire body is effected. From my perspective why that’s important is yes, the brain is involved as well. To think that Rheumatoid Arthritis is uniquely a joint condition is extremely narrow minded, we talk about Psoriatic Arthritis as a unique type of arthritis when there is Psoriasis as well. We have joints involved and we have the skin involved. The reality is the whole body is responding to this elevation of these inflammatory chemical call cytokines that are circulating from top to bottom that do penetrate the blood-brain barrier and actually weaken the blood-brain barrier and create inflammation in the brain. Yes, there is wholistic perspective, I think it’s a very important one. Because that’s how health and illnesses have been looked upon for the entire time we have been on this planet, except for extremely recent times when we have tried to segregate illnesses and body parts. Create doctors who specialize in these very specific areas in order to develop protocols that are drug-centric, that are dealing with symptoms that are related to these specific systems.
Ask the simple question, what’s going on in an autoimmune condition, 50 million Americans 3/4 of which are women, what’s going on. It doesn’t matter whether we’re talking about Rheumatoid Arthritis, Type 1 Diabetes, or Lupus, the final common denominator here it that the immune system is not functioning appropriately, it’s failing to differentiate between self and non-self. The immune system is reacting against the persons body and obviously that’s not supposed to happen. That’s what unifies these autoimmune conditions across the board and now we understand that this mechanism is also in play in Alzheimer’s. Many researchers now include Alzheimer’s Disease under the umbrella of autoimmune conditions. We have to take a step back and ask ourselves where is the problem, what is it that is regulating the immune system, where does the balance occur. We recognize now, oddly enough, that happens in the gut. It ultimately turns out that the gut is the area of the body that has huge sway over determining the set point of immunity, and even the set point for inflammation for that matter, basically they are one in the same.
What happens in the gut doesn’t stay in the gut, the gut in it’s roll in terms of arbiter of immune balance has huge influence over the entire rest of the body. When the barrier of the gut is breached and proteins and other issues from the gut get into the immune system they amp up the immune system and we have issues that occur far distant from the gut itself. Skin conditions, joint, brain, thyroid, issues with Diabetes, etc, that ultimately relate back to changes in the permeability or leakiness of the gut lining. Take a step even back from there, what we now fully understand is that the maintenance of the integrity of the gut lining, which again tends to regulate the immune system. The maintenance of the barrier function of the gut happens as a responsibility of certain good gut bacteria or probiotic bacteria. More importantly it deals with the balance of bacteria that live within the intestines. When we disrupt the balance of the bacteria, when we change the signature, change the fingerprint of what the bacteria in the gut look like, it jeopardizes the integrity of the gut lining and then plays a pivotal roll in amping up the immune system. When we talk about autoimmune systems whether they are brain related like MS, or joint or skin related, our focus must absolutely be the gut.
It’s taken a long time for people to really get hold of that notion because that traditionally has been the province of the gastroenterologist. Frankly for this to be something that a gastroenterologist to deal with because the downstream effect might be Type 1 Diabetes or Lupus, is really stretching the comfort zone in terms of what a specialist in the gut would want to relate to. I believe that the science now is really quite supportive of the fact that this breakdown in the gut lining leading to increased gut permeability is a cornerstone player in autoimmune conditions across the board. Here is the very exciting part of that story, when we finally get our arms around this paradigm and understand what a fundamental role is played by that one cell thickness lining of the gut. In terms of immunity we then can start to look at how we can develop programs to re-establish gut health. To rebuild that integrity and therefore regain balance over the immune system. That information can then be leveraged in a therapeutic model that can deal with autoimmune conditions across the board in a far more gentle way than simply at the end of the day administering medications to turn down the immune system, which with all due respect is somewhat primitive. It doesn’t focus on the cause of these issues if we look at things like immune suppression, it’s really fraught with potential devastating side effects.
Chronologically gut health begins in utero, and then at birth, and certainly food is a major influence. It’s probably the most important influence in a positive throughout the rest of our lives, but the negative issues are so detrimental, things like medications. Antibiotics, a wonderful study out of Denmark demonstrated a perfect correlation between the risk of Type 2, which is not the autoimmune Diabetes but it’s inflammatory non the less. The risk of Type 2 Diabetes plotted against the number of antibiotics received over the previous 14 years and the plot is virtually linear, meaning, the more antibiotics you’ve been exposed to the greater your risk of Type 2 Diabetes. Here in America we use antibiotics quite liberally, you have a cold, sniffle or sore throat, you go to a walk in clinic and out you come with a prescription of a very powerful broad spectrum bacteralicidal, meaning killing bacteria medication. Now that whole scenario is flawed on multiple levels, for one you’ve gone to a clinic because you have a virus and you’re walking out with a bacterial. It doesn’t make sense it’s like having your appendix taken out when your Gall Bladder is sick, it’s the wrong treatment.
Number two aside from the potential issues of helping to increase drug resistant organisms we know that even one single dosage of an antibiotic has a lifelong effect in terms of changing the gut microbiome, the organisms that live within the gut. It’s very sobering to understand that these medications that are used so liberally in our society have absolutely long term consequences. I think that we have to understand that these antibiotics are not a play thing and they’re not without risk. I reviewed an interesting report that was published the Journal of Translational Medicine back in 2013 in which they demonstrated, and it’s really quite fascinating. That many of the commonly used antibiotics, especially the fluoroquinolones and aminoglycosides which are groups of antibiotics, are not only toxic to bacteria but they are toxic to mitochondria, the energy producers of our cells. It was an extremely compelling research project that showed profound increase in things like free radical production in laboratory models that were of human cells exposed to antibiotics. Here is a positive take home message that these researchers demonstrated, is they pre-treated the cells with a simple over-the-counter health food store antioxidant called NAC, that the degree of damage to the mitochondria was profoundly reduced.
So yes, food is important but we have other issues, other factors in our daily lives that really need attention, and I would say that antibiotics is at the top of that list. When you consider that 70% of the antibiotics that are produced in America don’t even go into medicine, they go into livestock and poultry production. You can be very careful about not taking an antibiotic then you have to think about what you had for diner last night. Most beef in America, almost all of it is not grass fed beef if it is from factory farms, and the same with poultry. They are not pumped full of antibiotics because the animals are sick it’s because when an animal is given antibiotics it was discovered in the 1950s it makes then fatter, weigh more, and therefore of more value. We now understand that the reason that is happening is because antibiotics is changing the gut bacteria, changing the microbiome. Favoring the type of bacteria that actually change the metabolism and convince the body that it needs to gain weight. Dr. Martin Blaser wrote a wonderful book called Missing Microbes. He quite squarely pointed a finger at our over usage of antibiotics as playing an important role in the incredible overweight and obesity that we’re seeing in children and in teenagers. We have co-evolved with a certain expectation of what our microbiome in our gut should look like now suddenly we are turning the tables. We are changing the microbiome and it’s having powerful effects on our metabolism and even in terms of our own gene expression. What I just said was that our bacteria living within our intestines have a certain roll to play in changing the expression of our own DNA. The 23,000 genes that we have inherited from Mom and Dad they are to some degree affected in terms of their expression at the whim of the bacteria that live within us.
If we accept the notion that the point in the human body where the immune system is balanced is the one celled lining of the gut. Then we ask ourselves what can we do to preserve the gut integrity. How can we cultivate a dietary program that is designed to maintain gut lining integrity to reduce leaky bowel. Those of us in functional medicine we have been kicking around the term leaky gut for decades and now suddenly you read about it online and everybody is talking about leaky bowel syndrome. That is the cornerstone of every autoimmune condition you can think about, so what do we do. One of the recommendations that we make for maintaining the gut lining, because that is what’s most important in terms of immune function and regulations. That needs to be a diet that is lower in carbohydrates, lower in sugar, welcomes back to the table healthful fats, and really importantly it’s a diet that has lot’s and lot’s of prebiotic fiber. This is the unique type of fiber that nurtures the gut bacteria and specifically amplifies both the metabolism and the growth of the good bacteria who go about fixing the gut lining. Here is a powerful connection, foods that are rich in prebiotic fiber will make more gut bacteria that will then go to work and heal the gut lining and that will help balance the immune system.
What are those foods, jicama, dandelion greens, garlic, onions, leeks, asparagus, radicchio, these are foods that are really high in prebiotic fiber. Other vegetables have higher or lower prebiotic fiber, you can go to a health food store and buy a product with prebiotic fiber near the shelf with probiotics. The reason you’re seeing these products is people are getting the message that when they eat lots of prebiotic foods and when they take prebiotic supplements, they are nurturing the good bacteria in the gut and healing the gut lining. You can get a prebiotic from the African acacia tree and that tree emits a resin, a gum, that is then made into a powder that is a powerful prebiotic. The other part of the equation would be probiotics, actually consuming the good bacteria that will then help balance the gut and therefore balance the immune system. These are fermented foods like kombucha, kimchi, fermented vegetables, sauerkraut, cultured yoghurt. These foods are rich and teaming with good bacteria and do make their way through the stomach acid and do end up viable in the intestines where they go about healing the gut lining. In an ideal world we probably wouldn’t need to take probiotic supplements.
I think that the amount of environmental stress that we are exposed to is really a powerful call for supplementing the probiotics in the gut and amping up the level of the Bacteria. There are now some very powerful, very potent, wide spectrum probiotic supplements that are available in the health food store. I don’t think any of us is eating enough fermented foods so I am all over the notion that we really do need to supplement. In terms of what to look for in a probiotic I say read the label so that you are sure you are getting a viable number of organisms and that these things really do arrive alive. You can buy products that say it has 30 billion CFU’s, colony farming units, at the time of manufacture. But that really doesn’t tell you anything in terms of shelf life and it’s viability of a product, and in 6 months later after you bought it, after it’s been sitting at the health food store. You really want to find products that have a guarantee of shelf life in terms of viability with a fairly wide array of organisms is really important. There is some key organisms that I look for like Lactobacillus acidolphilus, Lactobacillus plantarum, Bifidobacterium longum, Lactobacillus rhamnosus. These are important organisms you should be looking for in products that you buy.
Even if you are eating fermented foods it’s not a bad idea to add the probiotics to your regimen. In addition the other important recommendations shouldn’t be taken lightly, sugar needs to be reduced dramatically. Just as a point, there is a big push now in the recognition that sugar beyond it’s effects upon the microbiome, has obviously metabolic effects that are detrimental. Therefore people seem to be gravitating towards artificially sweetened foods, beverages, chewing gums, even fiber for reasons that don’t make any sense. We are seeing that artificial sweeteners, they’re really becoming ubiquitous and incredibly the science has demonstrated that in terms of the threat to the microbiome that artificial sweeteners are actually even a worse risk. Obesity is dramatically increased based upon consumption of sugar free, no calorie beverages. It doesn’t make sense, seems counterintuitive that drinking liters of a beverage each day that have absolutely zero calories and no sugar and yet your gaining weight. The reason that happens is because of the changes in the microbiome that are induced by these chemicals, these artificial sweeteners.
To come back to what I do as a brain specialist, why would I care. The reason I care is because there is a very straightforward correlation between obesity and risk for dementia that the larger the body mass index the smaller is the brains memory center called the hippocampus. Beyond that we recognize that body fat is not just a storage depot of calories but acts as an endocrine gland and does therefore secrete. What body fats secrete is white adipose tissue, that’s the type that you gain as you get fat. It secretes chemicals called adipose meaning fat kinds, many people know them as cytokines. These are the chemical mediators of inflammation, it turns out that these cytokines that are secreted from our white adipose tissue are body fat. Not only does it get through the blood-brain barrier and then amp up inflammation in the brain, but they actually destabilize or break down the blood-brain barrier.
Now we’re onto our second blood-brain barrier in the human body, First we talked about the gut lining and it’s integral roll in terms of regulating the immune function and inflammation. Now we’re talking about the blood-brain barrier that we thought sequestered the brain and created the brain as being the sanctuary isolated from the rest of the body. It turns out that many chemicals can transgress the blood-brain barrier and these chemicals that mediate inflammation can do so, and at the same time they can open up the doors. They have free access, they can break open up the door, increase the permeability of the blood-brain barrier. Get in the brain and turn on inflammation, the cornerstone of Parkinson’s, Multiple Sclerosis, Alzheimer’s, Autism. It becomes a very big picture to look at and certainly beyond the scope of I think what medical specialists would want to look at and yet I believe this is basically a revolution in medicine and recognizing these obstructs.
Again our lifestyle factors are the most important point of intervention here not medication. It turns out that people taking Diabetes medication, while it may lower their A1c’s and their blood sugars, that Diabetes medications do not extend life in the patients that are taking them. There was an interesting study that was published in the New England Journal of Medicine, I think it was in 2009. Where they took 2 groups of patients who did not yet have Diabetes they were pre-Diabetic. In one group they put them on the medication Metformin, the other group got lifestyle counseling, exercise, and diet changes. What they found that was, after a period of time, that the risk of Diabetes was reduced in both groups. But the risk of Diabetes was much more reduced in the people who just simply changed their diets and exercised. What was even more compelling was that the risk of death in the drug group was twice as high as in the people who were simply told to exercise and make a diet change. We live in a world where we expect there to be an instant prescription or other remedy for our various ills but that isn’t the case with the medication that will lower blood sugar, they are not risk free by and large. I really think the time has come for us to jump on board with exercising preventive medicine on the front of it.
When we want to have a conversation about autoimmunity conditions and preventative medicine what does that look like. It looks like lifestyle changes that reduce the changes in the gut bacteria, it’s the diet that I just recommended, it’s being super careful about medications that you may be exposed to. Why, because some of our most commonly used medications change the gut bacteria like these non-steroid anti-inflammatory drugs that everybody takes with every ache or pain. These acid blocking drugs called proton pump inhibitors that are over-the-counter that everybody thinks they need because they have heartburn. These drugs change the acidity, the PH of the entire gastrointestinal system, and actually change the environment of the bacteria in the gut and therefore have dramatic effects upon the diseases that manifest because of those bacterial changes. In a recent study out of Stanford University, it was shown that the risk of heart attack in people taking these acid-blocking drugs is increased 14%. The risk of dying from that heart attack is doubled, simply from taking these drugs. The conclusion from the researches was the mechanism was mediated by changes in the gut bacteria. Again when you change the gut bacteria it leads to permeability or leakiness of the gut, that turns on the immune system which turns on inflammation. Inflammation is the cornerstone of coronary artery disease. When you walk through each of those steps you recognize, therefore, why there’s this connection between people taking these drugs and risk for heart attack. Medication is the third leading cause of death. The interesting thing about that report in the British Medical Journal and similar data that’s come out in American research, is that these are medications were used appropriately, they’re not overdosed or given to people who are allergic. These are drugs used for what they are intended.
Actionable steps you can take now is we know even physical exercise does have an effect positively on changing the microbiome. The dietary recommendations, the supplementation with prebiotic and probiotics are absolutely key. We have to in a very big way take a step back from these antibiotics and recognize that there is long term health risks from exposure to antibiotics which is happening left, right and center. It is the number one drug used in children under the age of ten years in America today, it’s very worrisome. I think that in this day and age where it’s sometimes looked upon as being trendy to be gluten free let’s just for a moment put that aside. Lets look at the science behind a gluten and why that might be relevant in terms of a lifestyle choice, in terms of relevance to an autoimmune condition. Gluten contains a protein called gliadin, and we have known for a long time based upon the work of Dr. Alessio Fasano, now at Harvard, that gliadin is directly involved in destabilizing the gut lining that relates to autoimmunity. His more recently published revealed that the response to gliadin in terms of gut permeability happens in all individuals, 100% of humanity.
The notion that celiac patients should avoid gluten is very sound. The recommendation that the people who have non celiac gluten sensitivity should avoid gluten, wheat, barley, rye and other foods that contain it as an additive is very sound as well. My very best recommendation is to stay off of gluten containing foods because while consuming foods that contain gluten may not cause a problem for you right at that moment it does represent yet another straw on the camels back. In addition to the antibiotics that you may be getting in your food, the chlorination of your water, the carbs and sugar that may be in your diet, your lack of probiotic and prebiotic foods. In looking at all the important inputs into a global program we have to absolutely include doing your best to stay off of gluten. When you realize that even muscular skeletal issues are effected by the whole process of inflammation and what does that do, it leads to pain. When we get rid of gluten, and in addition by eating no grain, you’re cutting back on your carb load and inflammation. That has a huge roll to play in terms of balancing the immune system and also in terms of getting over things like Fibromyalgia and chronic soft tissue pain.
The information contained on this site is for educational purposes only and should not be used as a substitute for diagnosis or treatment from a licensed physician. It is essential that you discuss with your doctor any symptoms or medical problems you may be experiencing.
M. Scherker medical researcher