Electrical Stimulation in the Setting of Secondary Progressive Multiple Sclerosis." MSRD, who is the Bionutritionist at the Clinical Research Unit. The title of their Medicine and Assistant Chief of Staff at the VA Medical Center, and Cathy Chenard, Multiple Sclerosis in the relapse/remitting phase where you have So I'll turn it over to you. The first to speak will be Dr. Wahls. Thank you very Welcome everyone to this month's Bench to Bedside Seminar. I'm really pleased to a huge success and I can tell you having Secondary Progressive MS myself and having acute symptoms get worse and gradually improve over a period of weeks to months and of course, Institute for Clinical Translational Science, which is all of you and you get close to baseline. So that's the remitting phase. After 10 to 15 years day to come hear our talk. I'm going to start off with acknowledgements. These are experience a 10% improvement on the fatigue severity scale that is considered familiar with SPMS, it's a disease, most people are initially diagnosed with fatigue are very difficult. You can take amphetamines, Provigil, and if you gradual steady decline. Usually the treatment that's offered is something like guys. So this is our study. Nutritional Neuromuscular Electrical Stim in the introduce our two speakers today; Terry Wahls, who is Professor of Internal kind of support from DJO, Clinical Life, TZ Press, which is a company that I own, more each week to help make this study happen and we're very, very grateful for most disabling symptom with Secondary Progressive MS and the treatments for much. I'm very pleased that all of you have come and taken the time out of your of diagnosis more than half will have converted to the Secondary Progressive our senior scientists who have been truly instrumental in helping me design a sound phase where you're no longer having acute episodes of worsening but you're having presentation is, "The Effect of Intensive Nutrition, Exercise and Neuromuscular profoundly grateful, but they still have often profound and total fatigue setting of Secondary Progressive Multiple Sclerosis. For those of you who may not be study and then I have a long list of study volunteers who are giving me 10 hours or taken those drugs it's a little tiny improvement for which people are the chemotherapy in the form of IV mitoxantrone or Novantrone in an attempt their support. The study is being funded by Direct MS Charity of Canada and we in to stabilize the patient so their rate of decline slows. At present there's no treatment that I'm aware of that restores function. I would also say fatigue is the disability and fatigue disability is the most common reason MS folks become unemployable. So, within that background in mind I'm sure you all know the reason we're doing this study is that I have Secondary Progressive MS. I spent four years in a tilt-recline wheelchair and then based on my personal review of the literature and discovery of functional medicine, I created an intensive nutrition program, an exercise program, neuromuscular electrical stim, massage, meditation and to my complete surprise not only did I stabilize my disease I improved to the point I can bike to work, ride horses and have the privilege of conducting clinical trials in others testing whether or not my interventions could, A, be tolerated and if people can tolerate them what happens? So this is really a feasibility trial. We were funded for 20 subjects. The IRB in their wisdom said do 10, give us a safety report. If everything is okay, you can do the second 10. So, we're reporting on our first wave of subjects and the intervention is essentially what I did that first year. I'll tell you when I put through that first application the pharmacy said no, there's no human safety data and so I rewrote the application doing just the exercise, meditation, massage and the diet without any of the supplements and the IRB said no we're going to disallow that. We want you to do exactly what you did and had me meet with a pharmacy. So we worked out what were the safety labs, what were the exclusionary criteria. So we are doing what I did that first year with the modification that people don't do electrical stimulation to the high extreme levels that I did. They do it at a much more moderate level. So IDN, that's the Wahl's diet, that's really a modified Paleolithic diet so there's no gluten, no dairy, no eggs. We ask people to have 9 cups of vegetables and fruit each day and that's 3 cups of servings of green leaves; 3 servings of sulfur-rich vegetables, cabbage, onions, garlic, mushrooms; and 3 servings of brightly colored, that's colored all the way through. Just color of the skin doesn't count. It's got to be colored all the way through, of vegetables or berries. We give the metholated, forlate, metholated B12, a bunch of sulfur, amino acids and a number of antioxidants. We teach them how to do meditation. We also teach them how to do simple self massage of the hands, feet, face and ears. We give them stretching exercises, we give them a test electrical stimulation session. We give them a big notebook that has a very detailed set of logs that gives them prompts of what to do every day, what they're eating, their massaging, meditating, et cetera, and what stretching exercises they've done. They come back in two weeks and we go through their notebooks to see where they able to comply with everything. If they were not, then we have a heart-to-heart and say, okay, do you think you could do it in two more weeks? We consented 12 people to be brought in and 3 of those 12 did not make it into the main study. Reasons were basically it's too expensive to take on this diet or the travel back and forth was too difficult and the third person had cognitive issues that were so profound she was not able to answer any of the logs for us. The outcomes that we are following, fatigue severity scale, it's 9 questions that you answer 1 to 7 and you rank how severely the fatigue is interfering with various aspects of your life. A number of self-reported scales, quality of life, the short form 36, MS spasticity scale 88. NARCOMS has a number of self-reported disability scales and the medical symptoms questionnaire is detailed and scored review of systems. Twenty-five foot walk at a timed up and go. A bird balance which is a measure of balance. We do progressively harder things and even I can't do them all yet. So it's really quite hard. Manual motor testing by physical therapy type of individual who can assess the trunk muscle strength and muscle strength of the legs and thighs. A cognitive stability index or if you're over 55 a cognitive CST, cognitive stability test. The Dkefs and Wais III we do subscales measuring language skills and verbal processing. Then we do mood assessments with Beck anxiety index and Beck depression index. Lots of data. What I'll show you is data that we presented at the 2011 Neuroscience Conference in Washington, D.C. on November 13th. So this is basically our first six months' data. So, the point I want you to see here is almost no one is eating any vegetables in the beginning. Okay, so we're right down here and then people do improve remarkably during the run-in because they know they have to and they keep it up fairly well. Some people have dropped down, but I will note even though they have dropped the lowest person being down to four servings a day, that's still vastly more than what they were at which was like .5 beforehand. So people are making big changes and they are sustaining them. Okay, I'm trying to clear. Okay. Now servings of gluten, dairy and eggs. I want you to take in here that everybody loves gluten, dairy and eggs. We're all eating lots of that and as a side bar that simulates the pleasure center in your brain. You get more dopamine release when you eat gluten, dairy and eggs. So, we asked people to give up food they love and by God they actually do. The out take is very impressive and people do report an occasional cheat and some of our folks when they cheat get to have severe headaches, fatigue, malaise right away. I'd say about a third of our folks can tell acutely if they get into trouble. Now this is our first estimate of a compliant score for the nutrition part, the daily servings of green sulfur and color minus six times the daily servings of the prohibited foods and people are keeping the scores positive. What this should highlight is we are radically changing how people eat and they're able to sustain this radical change. Pretty much everybody loses weight and we had concern because some people losing weight a little more quickly and we did make some changes so that we're watching weight loss and intervening when people are losing weight more rapidly than what we would like. People do increase their number of strengthening exercises, repetitions over time. The duration of electrical stimulation no one was doing electrical stim before we started, of course, and that does increase over time. Side effects that we saw. As I mentioned earlier, everyone loses weight on this diet and nausea and gastric problems we have a whole big long list of supplements and basically what we told people is the supplements are optional. If you have any perception of any problem with any of those supplements we want you to stop it and then call and talk to us and we'll sort through what we do with that. We also noticed that two people had headaches when they did the neuromuscular stim and that resolved when we reduced the current dose. The weight loss was a problem? It was only 5 pounds. That's not a problem [inaudible]. For most of our folks are overweight to begin with and as their weight comes down protein, ideal body mass, the weight loss tends to stabilize. We do have one individual who is losing weight more rapidly than we are comfortable with and she's being evaluated for the causes for her weight loss. Now, I'm going to show you some of our outcomes data. I have to put on my glasses so I can read this. This is based on our six-month data. So, the Short Form 36 is a quality of life scale 36 questions and there are multiple subscales. What I'm showing you is the general health subscale. We had an improvement from a baseline of 41 to about 71 and that difference is significant at .008 level. Physical role improved at a level of .012. Pain over time improved .014. And there's a trend towards improving energy of the P value of .112. There were not meaningful trends in either depression or anxiety. Now, I would make the note that we're quite surprised that there was very little depression in the people who enrolled in MS in our trial. That's actually atypical because depression is very common in MS. My assumption is that in order to be willing to come into a study that demands as much as we demand because we change what you eat, we teach you to meditate, massage, exercise. We take away all of your discretionary time for the first three months. You have to have a lot of resilience and a tremendous support at home to be in my study. So Fatigue Severity Scale. As I mentioned earlier, fatigue is incredibly hard to treat. It's very resistant. People take basically amphetamines, Provigil, and you get an improvement about 10%; that's a treatment success. At baseline everyone except for subject 9 had fatigue score greater than 5 typical of what you see in MS. At three month, the average fatigue went from mean of 5.7 to 3.8. That's pretty phenomenal. At six month fatigue score was 3.9. That has a P value, which we don't have written down here but was statistically significant and clinically significant for the people that you see the stars with that's a clinically significant change in fatigue. When we look at the MS literature, there's no literature that comes close to having this kind of effect size. Okay, same thing. Walking speed and what we have in stars for you are the people who had clinically significant improvements in their walking speed. So that would be subject 1, subject 3 and subject 11. We had the same people come back at 9 and 12 months and we're seeing more improvements the longer you've been at this. It takes a long time to grow the amount of muscle that you need to really improve your gait. I will also say that we've had one subject, subject 5, whose walking speed had clinically significant decline. I also will tell you we had one subject, 11, who came in with a cane for short distances, a walker for long distances, who can now jog and we have a video of her jogging. Subject 3 came walking a cane, could not pick up her foot at all and we now have a video of her climbing seven stairs. So we're getting calls from people who are saying, oh, my God, Dr. Wahl's, I can now do X and I hadn't been able to do that for several years. Okay, so that's the end of my show. I'm going to hand it off to Cathy who is going to talk a little bit about the nutrition side and we kept things fairly short so we're very anxious to get your comments and feedback. [ Silence ] Good afternoon everyone. I'm a little curious as to who all is here today. I recognize some folks from the ICTS and I know some folks are working with Terry. So are the rest of you doing research or research coordinators or [inaudible]? Research coordinators raise your hand. Trainees and scholars thank you for the terminology okay, a few of you, okay, and Terry's students. I want to acknowledge you for all the work that you do with Terry. So my name is Cathy Chenard and I'm the dietician that works in the clinical research unit here and what I want to do today is to talk about how we are providing support for Terry's study and to, all right, [inaudible]. [laughter] [Inaudible]. Thank you. I'll get it started. I'll use the advanced clicker. You're right. Thank you. Okay. All right. So, what are we talking about today is how we're providing support for Dr. Terry Wahl's study. Let me start out by explaining the overall picture about why we exist, why there's space down three, four and five that the institute has dedicated for the nutrition service. We exist here to provide support to investigators to assist them in achieving whatever their goals are for their research study and what the project is then we tailor the services [inaudible]. We have a facility as I mentioned down in the Clinical Research Unit on 2 Boyd Tower. We have a metabolic kitchen that is attached to a dining and also multipurpose room that can be used for patient education meeting and other uses. Then we have a body composition room [inaudible] body fat for folks. The institute funds a registered dietician, a part-time registered dietician, which is myself, and then we a metabolic kitchen supervisor. And the services, the key services that we provide to investigators include assisting them with developing and implementing the nutrition portion of their research study and also provides services for feeding [inaudible] that might be a [inaudible] how patients are fasting and for a long period of time we provide general food services for a specific diet such as for Dr. Wahl's study. We look at what people eat at home [inaudible] and body composition and then we provide some services for helping to teach students as well as [inaudible]. So, what I'm going to do now is go through our main key services and share a little bit about how this applied to Terry. So in terms of developing and implementing protocols, we can assist investigators with a variety of things that are listed on the slide there, depending on their needs. In Terry's case I remember it was quite a few years ago that you had called on the phone looking for I think [inaudible] or something very, very long time ago and shared a little bit and I remember thinking, boy, I hope she [inaudible] really interesting to have you come back and be able to help provide services for you and a lot of times we do get calls from investigators. Sometimes we never hear from them again and know where they're headed with their research but Terry was one of the investigators [inaudible] area of investigation and did come back [inaudible]. Some other services we've provided for Terry, she had asked for some input and some feedback as to how we might be able to enhance [inaudible]. So, we had reviewed some of the dietary logs that she's asking subjects to keep [inaudible] assist in finding those. We have provided nutritional literature, references, grants that she's writing for [inaudible] and also assisting with looking at dietary data. One of the big questions that we helped with in terms of study design for her was that Terry was interested in looking at what [inaudible] they started the diet and comparing it with when they are on the diet, on the study and since she was enrolling the participants right away there was no time to do any kind of elaborate data collection before they start the study. So, she was interested in using a food frequency questionnaire. It's basically a list of food items and then participants are asked to indicate how often they eat them in the past year and the [inaudible] on the screen there. The challenge with Terry's study was that [inaudible] investigators interested in nutrients that are not common nutrients that might be included in nutrient databases or [inaudible] and, of course, being [inaudible] study with very limited funding we had to look at the instruments that would best provide the nutrients [inaudible] cost. So we reviewed several food frequency questionnaires and decided on [inaudible]. So, assisting with, we assisted with setting up protocol. The second area that we assisted [inaudible] subjects and here we have a picture of Greg Pete, who is our kitchen manager in our metabolic kitchen, and we can provide a variety of controls on meals where we would carefully calculate and weigh all the food that participants ate and really that's [inaudible] if you want to do a controlled feeding study where you need to know people are eating [inaudible] then the metabolic kitchen and our services are available here to you to [inaudible]. Terry's study did not need that level [inaudible] so in terms of assisting the participants in learning about the diet and what we had offered to her that we would do is that for the screening visit the diet is new, they might not have heard of this and we wanted to give them a positive experience eating the diet. So, we had developed a menu that participants could collect them where they would be eating [inaudible] Dr. Wahl's diet for the day using foods that are commonly available [inaudible] say, oh, gosh, it's tasty, it's filling and that was our intention by offering this. Here you can see an example of the research menu that we provided. It has [inaudible] she recommends that include various components, [inaudible] et cetera also has an absolutely fabulous [inaudible]. Here you can see categories that participants select from and how they're categorized so that they can [inaudible]. Before I move on to assessing what people eat I do want to mention since we're talking about food that [inaudible] would be helpful would be for people to have food samples that they could come in on a screening visit and take home with them so they wouldn't have to go to the store and [inaudible]. So, in case you have never seen some of these products, I'll go ahead and pass these around. We have gluten-free bread. We have some different seaweed products and we also have algae [inaudible]. I don't know if you noticed that the algae and the kelp were part of the smoothie ingredients there that we make for the participants. We also have some [inaudible]. [Inaudible] powder. Lastly some clay powder. This is not for consumption; this is for making a mask that you apply to your [inaudible]. All right the second area that we assist with is assessing what people eat and Terry mentioned the food logs that the participants keep each day. That's how she was able to determine [inaudible] their gluten and dairy and eggs and increase their fruits and vegetable intake, but from a scientific standpoint we wanted to collect [inaudible] information. So one way we were doing that is to do the food frequency questionnaire to administer that at the beginning and the end so that we can look at dietary changes and then we also are looking at nutritional adequacy of the diet and we'll be doing that primarily through 24-hour recalls. So, the food frequency questionnaire is looking at the overall general kind of average nutrient intake and [inaudible] that so we wanted to really get specific and to drill down on specific days as to what participants were eating. So, we're calling them on the telephone and asking them what they ate and drank the day before and what supplements they take and then we'll be looking at [inaudible] and that was a sample of Terry's diet. [Inaudible] would work and so we'll be looking at nutritional adequacy. Here's an example of the slide that looks at the probability of adequacy. Dietary reference intakes, the Institute of Medicine they have a procedure that looks at whether the diets are adequate or not and we'll be following those guidelines needed for the study. [inaudible]. I need to get a slide that shows that to compare. So, yes, most Americans or many Americans will not be at the probability of like 99, 98. Fruits and vegetables are very [inaudible]. The next area is assessing body composition and we do have a variety of methods that we can [inaudible]. The picture on the slide here is a little fellow who was measured in our bodpod, which is a body composition [inaudible] and for Terry's study we didn't start out looking at body composition; however, doesn't the changes in the weight and the weight loss [inaudible] to be monitoring that so when the new cohort comes in the beginning we'll do their body composition [inaudible] muscle mass [inaudible], but if they're mobile a lot [inaudible]. So we are going to be doing body composition measurement. Then lastly is we do provide services for teaching research [inaudible] students and let me just say that we provide minimal assistance with that [inaudible] and the dietary portion protocol what's expected [inaudible]. For complicated dietary interventions [inaudible] big changes in their diet I recommend that investigators [inaudible] in the blue who is professor in the College of Health and Nutrition Center, she and her dieticians [inaudible] with her and so Linda has been providing assistance [inaudible] big change that people are to make. The last point I would make about subjects and students here is that we periodically have either volunteers or students who are interested in a nutrition research [inaudible] and if they are given an opportunity to select what protocol they might be interested in working with during their time with us [inaudible]. [laughter] Her study is very popular with people and so we've had some students who have developed some handouts that participants get and here are some examples of them [inaudible] have in their notebook a little information about what the heck is kelp and [inaudible] help and overview. To sum this up our nutrition Greg and I are here to assist [inaudible] or investigators, research coordinators, anyone with [inaudible]. Stop by and see us some time. We're in [inaudible]. [Inaudible] very, very happy to assist you at any part of your study or your beginning when you're looking at things to gradually submitting a protocol or [inaudible] all these wonderful protocols that the ICTS [inaudible]. Don't go anywhere. They have questions for us for both of you. So, I invite you guys to have questions about our study design, our protocol, our findings, suggestions, comments. Yes? I was wondering how adequate the USDA standard reference database is for assessing some of these [inaudible]. That question is for you. I'll follow it up. I've asked Cathy about iodine and sulfur in particular because for my interpretational literature iodine and sulfur are very important for detoxification pathways and then Cathy told me that those difficult questions to answer. The standard nutrient databases that are commonly available do not include iodine or specifically sulfur as a nutrient so your question was how adequate is it to look at this particular diet. Actually for collecting the 24-hour recalls we're not using the USDA data. We're using the nutrition data system for research, which Joanne, I know you're familiar with. So, it does include some other nutrient components that would not be part of the USDA [inaudible] and the Harvard Food Frequency Questionnaire they also had included nutrients where they had dieticians who were very knowledgeable about food composition who would add some of the other components and then would assign their reason/guesses to what the composition would be based on looking at the nutritional literature and the analysis that might have been published for [inaudible]. There definitely is a need for more information and sometimes looking at nutrients that are not available there is very labor-intensive and time-consuming process. If you really want to look at that, you have to go back to the literature and pull the information together. That answer your question? Thank you. Any more questions? Yes? [Inaudible]. So here's the sequence. I put the protocol, first I submitted it it was approved sort and then the pharmacy and therapeutics committee, I correctly said there's no safety data and this is a large combination of supplements we're asking people to take and I acknowledge that I put the cocktail together for me I did it based on animal studies. So there's only a human experience of one. The head of the VA research told me said, Terry, I'm looking at the tea leaves, you'll never get this approved if you leave the supplements in. So rewrite it, take all the supplements out. I did that and then the IRB disapproved it and the chair called me in bless his soul and he said, you know, actually the IRB is very excited you want to do this, we want to support you. So we're going to direct you to put it all back in and meet with pharmacy, let them tell you what are all the safety labs you need and what are the exclusionary criteria you need to keep it safe and we'll do just 10 and you'll give us a safety report before you do a second 10. I really don't want to appear to be criticizing the pharmacy committee because I think they were correct. There's no safety data. I was asking people to take a large number of supplements. So, they were appropriate in asking me to ramp up my safety labs considerably, which we did, and to have a phased-in approach. We'll do the first 10 ensure safety and we have learned to taper in the supplements more gradually and have a very low threshold for telling people that that supplement is not agreeing with you, you don't take it. [Inaudible]. So we give people a large list of B vitamins, sulfur, amino acids and antioxidants. As they gradually ramp those things up, what will happen in your body is I'm going to take all those toxins that were stored in my fat and metabolize them and if my phase one enzymes are more efficient so my phase one liver enzymes are more efficient, I generate a lot of [inaudible] that my phase two enzymes will then conjugate and make that compound water soluble so it can go out in my bile. But if my phase one enzymes are over activated, my phase two enzymes are less efficient because of my own genetic vulnerability, I can increase the toxicity of my compounds that have been safely stored in my fat and make myself much more [inaudible]. We could inadvertently put people in circumstances where they're taking toxins out of their fat and swapping them over into their brain. So, I think it's important that as we go into our second wave I've stretched out the introduction of the supplements and we have, make it much more explicit, much clearer that if there's any sense of problem you stop the supplement so that we don't inadvertently create a problem we're pulling toxins out of the fat and switching them over to the brain. That's all theoretic, but it's certainly one of the concerns that I have. Yes? [Inaudible]. Yes. [inaudible]. Well, we're freezing blood. I'm a vampire. So, I freeze blood at baseline and then at 3, 6, 9 and 12 months. The next thing I'll be doing is writing grants so we can pay for some very interesting studies. One of my senior colleagues, Gary Buttener, would be very interested in doing some blood analysis beginning and end. My assumption is that we're reducing reactive species and we're reducing inflammatory cytokines. If we did a provocation on heavy metals, that we're probably reducing body burden of heavy metals, solvents, plastics, pesticides, everything else that we all have stored in our fat. That also presumes since the average American eats less than three servings of fruits and vegetables every day, therefore, the average American really is starving their brains for the nutrients that we know brains need in terms of the B-vitamins, minerals, essential fats, that we're fixing the micronutrient deficiency, we're improving reducing oxidative stress and reducing inflammation. Unlike most sensible researchers we're not doing this molecule by molecule; we're doing it in a very systems fashion. So we're affecting all sorts of biologic systems as we go. Yes? [Inaudible]. Wow, that is a great question. They just asked me are you doing any long-term follow up. So, as the first 10 and there's only 9, as the first 9 are winding down at 12 months, they cannot imagine giving up the electrical stim device and so we put in a modification. We do have approval to extend it for a three- year study. So, people get their device in the years two and three. What we're doing is saying, okay, you can take the supplements that you want, you can exercise or not, we hope that you will, but what we're curious now is to know what you decide to do and what happens longitudinal. So, in the first four that have come through at the end we've [inaudible]. [Inaudible] the generally consensus is I will largely follow the diet. I may experiment and see how I feel if I occasionally have a forbidden food and see what happens, but everyone is telling us anticipate largely following the diet. They anticipate largely continuing the EStim and the meditative practice that appears to be something that people are going to continue. I'll say the massage and meditation probably has the lowest compliance rating. They do that maybe just 5 or 10 minutes a day, but in terms of lifestyle management we certainly have changed people's lives in a very big way. I think it will be very interesting to see how much continues now that I've said, okay, you get to do what you want, if you stop EStim, we need the device back but otherwise we'll see you in 6 months, 12 months, and 24 and we'll see what you're doing, how you do two weeks of daily logs before you come in so we have a sense of what you're eating and what you're doing. [Inaudible]. My sense. So, I'll tell you based on my personal experience if I go off the diet let's say I get in some gluten inadvertently I will have a flare of my face pain, which is basically trigeminal neuralgia, zings of pain, that will make me unable to speak, talk or move. [Inaudible] enough that I assure you I do not go over my diet very often because I've done that a few times. It's just been completely incapacitating for me. When I was very clever, we programmed my device so I could stim, you know, continuously. I loved it, but the device burnt out and had to ship it back and so I had to go 48 hours no stim. Well, I didn't like that very much either. Interestingly enough I never became tachycardia, [inaudible], I didn't have high blood pressure so I said, okay, I'm not in withdraw but I definitely do not like not stimming. So, when you stim, you release nerve growth factors, beta endorphins. So you couldn't make the case that maybe I was a little, had some level of addiction, certainly craving going on for that EStim. Now, I'm four years into this and I have just in the last month weaned myself away from EStim. So, my sense is if you don't fix your diet, you'll go nowhere. If all you did was fix your diet, do massage, meditation, I think you might be able to recover but you'll recover far more slowly because if you don't exercise and rebuild the muscles, you may recover the fatigue but you're not going to recover much for your walking. If you do the EStim, you'll make more nerve growth factors which will stimulate the remodeling and repair work that's going on in your brain and spinal cord and the endorphins will lower the inflammation. In our group of 9, we have 2 people who tell me that they can tell if they inadvertently got into some gluten or dairy, that they have severe headaches, fatigue, and it takes about two weeks to clear. Sounds exactly like me. Okay. The other folks could have an occasional indiscretion and what they discover is after about a week their fatigue begins to come back, pain increases. So for those people I think the problem is that food allergies but the bacteria species that live in their gut. As you know or may not know, we have a trillion cells, us, but we have a hundred trillion bacteria, yeast and parasites living in our bowels. So you and I are outnumbered a 100 to 1. If you have the species that our species grew up with for 2 1/2 million years, I call them the old friends, their metabolic byproducts will diffuse into my bloodstream and contribute to my health as in Vitamin K-2 or if we have the sugar loving trouble makers, their metabolic byproducts diffuse into my bloodstream and confuse the heck out of it ramping up my inflammatory cytokines and increasing the probability that I'll have an autoimmune disease, cardiovascular disease or cancer. So I think the diet and the second wave I'm trying to impress upon everyone this is not about gluten sensitivity or food allergies although you may have them. It's really about shifting the bacteria, protozoa, parasites in your bowels to the old friends that our species knew for 2 1/2 million years and to do that I want you to eat the way our ancestors ate 50,000 years ago. So that takes out flour, sugar, high-fructose corn syrup and that's actually a little tougher than just going gluten free, dairy free. Yes? [Inaudible]. So, our subjects have been on conventional medicines. They've been on Avonex, Betaseron, some subjects were on no disease-modifying drugs because neither Avonex nor Betaseron are approved for Secondary Progressive MS. I've asked everyone to stay on their current drug regimen and to work with their neurologist. They asked me can I stop my drugs say no, I'm not your treating neurologist. I'm only the study person. So, I want you to stay on your drugs and work with your neurologist. Now some of our subjects, 7 out of 9, have had marked improvement in their fatigue scores and are feeling remarkably better. So they have worked with their neurologist to some degree I hope because they have gone off their prior treatment agents and I mean it's really quite striking just looking at how people look from their enrollment day to the 3-month, 6-month, 12-month day. You see the years roll away and the person's vitality increase. It's stunning. Cathy may have a comment on that. Am I exaggerating, Cathy? Subject 1 she's just glowing. She's getting, she's lost a bunch of weight, she looks great, feels great and her spouse, we asked the spouses to eat the study diet in the presence of the study subject. He's lost 30 pounds as well and he's feel great. Families are doing very well. Yes? [Inaudible]. Right. So, two servings a week of a starchy vegetable or a gluten-free grain. I am, however, telling the second wave that the people who have done the best in our study went paleo and didn't even do those two servings a week, but you know psychologically it may be easier to know that, yes, I could still go have sushi with my family on Friday nights so the study does allow two servings a week. With [inaudible] I'm telling folks I think going completely paleo having no grain whatsoever is likely superior. [Inaudible]. Okay. Cathy, where is the niacin coming from? [Inaudible]. More questions? [Inaudible]. So, we have, the question is this is a big change GI wise so how do people tolerate that? So, most people come in not pooping, maybe pooping once a week, once every other week. So, constipation is absolutely a huge problem for MS folks. I have one lady who, and people bless their souls, I tell them to have 9 cups of vegetables and by God they come pretty close. So she was working on her three servings of greens and the poor soul her bowels just could not handle that. She was really pooping way more than once a week like several times a day and so called and she had a GI bug that added to her diarrhea, she was pretty miserable. I said, okay, so we backed away all the sulfur amino acids are reduced to her servings of grains. The bowels got happy and we had, added just one sulfur amino acid but that worked out. For some people the sulfur amino acids will be associated with diarrhea and we listen to that, we back off, we're not interested in giving people diarrhea but I am very interested in making people poop twice a day, three times is even better, but I don't want people to become incontinent and certainly people with MS do have not a long warning time between knowing they have to poop and being able to get to the bathroom. So, we are also sensitive to that and we know, I'm presuming, I don't know this, but I am presuming that I design the diet for myself to maximize the ability of my liver and kidneys to remove toxins and so I'm telling everyone that I'm presuming that they are like all of us and have heavy metals, plastics, solvents in our fat because if you measure babies and cord blood they all have about half to two- thirds of the various petro chemicals that are searched for. So, we presume everyone is toxic and going to be mobilizing toxins in their body. We want them pooping several times a day so they aren't recycling those toxins back into their brain. More questions? Yes? [Inaudible]. Yes. [Inaudible]. Oh, absolutely. We tell people we want them to go organic. I am not when people call wanting to be in the study one of our screening questions is can you cope with a 30% increase in your grocery bill? When I asked our study participants to tell me what was the percent increase the most consistent answer I got was 25%. So we made it 30 because I didn't want to underestimate how hard this is or how complicated and when I'm out speaking to the public I get this question a lot. Before I started this I was taking about $2,000 a month worth of drugs none of which, you know, I'm not taking those anymore. I still take [inaudible] and some [inaudible] and that's it. So, $2,000 worth of disease modifying drugs or $2,000 worth of food, you know, so plus I was looking at becoming bedridden, having to go out on early disability, thinking about nursing home, and now I don't have to think about those things, but this absolutely is more expensive. In my clinical practice, I see folks who are at the VA a lot of folks who don't have a lot of money I talk about getting your gun, getting your bow, go hunting, learn how to forage. I see a lot of folks who are former rangers and they like that, find that very exciting. We also talk about square foot gardening, community-sponsored agriculture, buying your food directly from a farmer and realizing that if you quit putting all that broadly fertilized or pesticides on your lawn, it's very easy to grow edible food and Iowa is absolutely filled with all sorts of edible greens and food. More questions? Is this diet recommended for people who don't have MS? And what modifications would you make for people who don't? Thank you so much. I love that question. [laughter] So, in my clinical practice if I see anyone who is overweight who is interested in weight loss, I tell them that this great [inaudible] supports going on a paleo diet is more filling and be able to lose weight without feeling that starving. So weight loss. So, people with diabetes I tell them that I have literature that says blood sugar control is superior on a paleo diet. Heart disease. I have literature to tell my patients that lipids improve on a paleo diet and that endothelial function is better on a paleo diet. Mental health issues. I tell people that if you go on a paleo diet you're likely to have better mood, better energy, less fatigue. Autoimmune issues. I suggest a paleo diet because you have a lower risk of autoimmune flares and that you're more likely to have the bacteria living in your bowels that are associated with better health than the bacteria that are associated with autoimmune problems. So in my practice, people who have a chronic disease who are open it's sort of a staged approach. In my clinical practice I say to everyone I see including the residents it's 9 cups of vegetables everyday; 3 green, 3 colored, 3 sulfur. Depending on the person I may tell them go gluten free, dairy free. If they have an autoimmune problem or a weight problem, I push paleo. If I think they have a toxic load problem, I also push paleo. [Inaudible]. So paleo is greens, roots, berries, meat, fish, eggs. No grain, no potatoes, no dairy and probably no soy. Yes? [Inaudible]. Could you repeat the question? I want to be sure I understand correctly? [Inaudible]. We've not done that kind of analysis. I have, I'm often, people ask what's the vegetarian equivalent and I have to say that I came to this through my understanding of the paleo literature and as I review the nutrient density of diets, the paleo diet has more vitamins, minerals, essential fats per calorie than any other diet that I've been able to see and that's why I chose that and, of course, I had the incredible results for myself. There are case reports of the raw vegans doing well and being a cure for MS. There's also the China study which promotes lots of vegetables and only a little bit of meat and Linda and I are talking about trying to create a protocol that would compare the China study diet, the Wahl's diet, which is a structured paleo and a standard American diet and see how the three diets go. The vegetarian my interpretation of the literature and, of course, this is simply me, I absolutely can be wrong, is that because a vegetarian cannot get enough B12 I don't think that we'll have optimal health as vegetarian. You may be able to compensate by taking supplemental B12 and B complex because there are lectins in proteins and legumes you could decrease that by sprouting the lectins, sprouting the grains and legumes for three days before you eat them. The other downside is that it's going to be a much high carbohydrate load in vegetarian diet which will shift the bacteria more towards that sugar-loving bacterial load, which increases the risk for chronic disease. So those are the tradeoffs. I know people are vegetarian for a variety of spiritual needs that I don't want to be able to adequately respect. I know that was sort of a hedged answer, but about as well as I could do. Are we having to wrap this up? I have two jobs for the seminars. One is to start on time and the other is to end on time. Thank you. But so I wanted to let you know our hour is up and I wanted to also know if our speakers would stick around if you have additional questions for a few minutes. Yes. Okay. Absolutely. Thank you very much for an informative presentation.