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Treating Oxidative Stress in Dementia: A Role for Lifestyle Medicine

Ross Grant

Presenter

Dr. Grant is a biochemical pharmacologist and is currently head of the Australasian Research Institute based at the Sydney Adventist Hospital. He also holds an academic position in the department of Pharmacology, Faculty of Medicine at UNSW. He has previously been director of SDA Medical Laboratories in Malawi, Africa. 

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  • December 7, 2014
    9:30 AM

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And one of the things that we want that we do and that we're focused on in doing our research institute there at the hospital is to be able to provide resources but it's conceptually intellectually as well as we hope practically and as a couple of things that we're working on relation to particularly what we called a wellness profile for being able to give to G.P.'s to be able to use a lot more efficiently but essentially that concept of where lifestyle and everything fits in now. I know in a clinical practice you getting along and they're using a lot of techniques which you've been taught etc But one of the things that I like to remind even my clinical colleagues at at Sydney hospital sitting at his hospital is that nothing happens clinically without They first being a shift by chemically and we really need to know what's happening behind the scenes in order to be most efficient about how we apply. So in other words taking on a medical science approach now what I'm hoping to do this morning is give you a little bit of an insight into potentially one of what is I think one of the most ineffective or the areas where we are actually in terms of current medicine where we have probably the least effective impact and that's clinically. And so if we can understand that a little bit behind that's dimentia still one of the top three causes of death in Australia. So if we can understand a little bit how it is produced and then see whether or not lifestyle which of course we are privileged to have that perspective from over a hundred fifty years ago. So we are looking in the right direction but let's look and see whether or not lifestyle might even have an impact in one of these huge areas where there's literally hundreds of millions of dollars in fact there are billions of dollars if you include all of the drug trials etc that are going in trying to work out how can we stop dementia and in fact the answer might be a lot closer than we think. So it is going to be a bit technical. It's nine thirty Sunday morning you're all bright you've had a great service rested. I'm hoping you're going to be with me. You'll get feedback form if you can just say no. Sorry we didn't really like that at all. And that way I can improve on it by possibly not doing it again. But let's have a look so trading now this concept of oxidative stress and I some of you have heard it before. I'll get a little bit more detail about that as we go through because we think that that's actually that if you like there's lots of things that can contribute to it but this is probably that point that final coalescing point in the biochemistry that we think that ultimately you end up with the changes to the body so let's have a look definition this is easy. We'll go through it pretty quickly. We're getting a progressive and irreversible loss of neurons. That's not going to be a surprise to most of you from specific regions of the brain affecting cognition So basically you're losing your arms and at least in the neurodegenerative dimensions there are talks of dimensions where you're just getting the not functioning so well. But we're actually talking about loss of neurons themselves and while I'm not going to show it here of time you'll actually see you know parts of the brain that are literally they're becoming smaller and. Because of the fact that your loss of neuronal loss. That's what we're looking at. So there's lots of different types of vascular dementia infectious diseases isolated dementia complex in fact I did a lot of work around my Ph D. but then Alzheimer's Parkinson's frontotemporal dementia Cook's idea of Huntington's mitochondria think of a lot of these etc Lots of things actually result in this type of thing there's no exam on this so you can just relax and enjoy it. But really the main choose from a variety of those things and I've put them essentially in order although I had to make it complex is not absolutely struggling through into ALS oncet cetera big burden in society over three hundred thousand strains currently affected predicted to be nine hundred thousand by twenty fifty each week there's more than seven hundred new cases of dementia about one person every six minutes that's not bad even in a country like Australia which is not very big and you will cost one percent of G.D.P. Now I've seen. Because it just depends on who actually puts these figures out up to six point five billion in a in associated costs others talk about around four billion. But either way it's a huge amount we're spending a lot on it and the expectation is that that's going to go up in a huge amount by a not too far away. Couple of decades. If you had a look at what's causing the main cause of this it's the Alzheimer's type dementia. But then from the temple to mention these are there's a lot of similarities between it being time between these but I'll focus mostly on Alzheimer's disease. So basically the main point of all of that little bit is that dementia is a big problem correct. And certainly for those of you in general practice I mean it's one of the things that your patients particularly the older ones are very concerned about. So they're worried about getting dementia or Alzheimer's or as they say old timers disease. So up to seventy five percent of Alzheimer's. And we know the clinical presentation it's classic it's one that most people know. Gradual loss of short term memory problems finding or speaking the right word when so far as we go down this list it seems like most of us have got this inability to recognize subjects forgetting how to use simple ordinary things such as a pencil forgetting to turn off the stove close windows a locked doors and mood and personality disorders depending on Ultimately the global dimension that occurs and look there's great stories but one of the best I can remember is a particular gentleman who'd been given a car by he's his daughter and he take took this new car a little Ford Focus and he drove it out somewhere forgot where he was going. Forgot how to get home so he parked it with the key still in the ignition into somebody's driveway and then went wandering off. Not sure exactly where he was intending to want to but he went wandering off. Eventually the police found him and took him home but nobody knew where his car was and so the dog's going Dad you had a car where is the car will you didn't know where the car was. Nobody could find the car and two weeks later the police actually found the car. With Well the person who had owned the house that he driven into had must have thought that I got a Christmas present and was actually driving the car around. Now I do wonder about the possibly some of the morals of the person who did it but in any case this is obviously where somebody has significant cognitive impairment of the L's on this thought now I'm going to go into this in too much but I want to talk about the fact just briefly that they what we call cholinergic neurons some of you'll know what I mean by that but essentially you've got these neurons and they use different you know when one of your own connects with the next one. It actually releases a little chemical that goes across this sign up to cleft and then excites the next one and away you go. These happen in fractions of a second. Now there's many different types you would know that in depression the parts of the Aries associate with that in this the serotonin bit right and if you're going to the feel good so like Dover Maine is one of the main ones. It's also those reward pathways for people who get hooked on things where is this type one it's actually uses as a toll calling Now you might know that want to talk only and also used in what we call the neuro muscular junction so actually to activate muscles but it's the cholinergic neurons that start to die off first. Now the reason why I'm telling you that is that when we come to the treatments so the current therapies. So we're losing the cholinergic. Now does anybody know there will be plenty of people who knows about that I mean which ones dying often does in Parkinson's disease the dogman urge of neurons. Yes So of course you've got a dozen neurons there dying in particular tract and what is the treatment for Parkinson's currently essentially trying to increase doesn't mean within that part of the brain is actually stopping the neurons from dying. Now it's not it's just increasing the amount of Doesn't mean so that the neurons that are left have to work harder. It's a little bit like the I maintain there's not enough people actually to help them help people to live work a lot harder. Most churches function that way too. So that's exactly the treatment surgery what is that. When actually stopping the Parkinson's disease stops the symptoms sometimes quite effectively and for a few years but actually doesn't stop the death of the neuron So actually you're not preventing the Pakistani as well. It's exactly the same with Parkinson's. Sorry with Alzheimer's so these colonist rise in heat it is things like Techron etc These are called mysteries and here is what they do is actually inhibit the enzymes that break down as tall calling so that there's more as a tall Colleen available for the neurons that are left and make those work harder. Now the trouble is that in Alzheimer's it doesn't work anywhere near as well as what happens in Parkinson's. But that's the treatment at the moment and that was the thinking very limited benefit that come out of it. And there's other things that can be given because of the fact these people will often get depressed for good reason as well as later on associated with some bit of neurons but then the antidepressants notice that these again are symptomatic treatments. Now somebody said you know in fact it was one of my students who said Oh so these really do affect your memory do then possibly thinking that she was going to go and find some so that then she could improve her memory and well not quite in that way and certainly wouldn't benefit. But in any case. They are symptomatic treatments there's a reason why I am telling you that many of you will not but it's because it's symptomatic. It's not preventing the course of the disease and in fact these are quite ineffective relatively speaking. There is one other what we call the disease modifying treatment which is these in India receptor antagonists that maintain everybody got very excited about them I won't go into the mechanism but unfortunately the evidence is lacking for a benefit of the nineteen models on this and there is neither evidence for its efficacy in moderate Alzheimer's and we know it doesn't work in advanced Alzheimer's this is the route of Gene twenty eleven. Basically very very limited data to suggest. These things actually work. In fact what's interesting is that the men team is targeting. And I want to get too technical here but it's actually targeting a process which actually produces free radical damage within the neuron. So when I talk about oxidative stress this is trying to target that by this particular receptor system this is what's called a glutamate subtype type of of receptor but in any case it's actually trying to prevent that within your own bottom line to all of this is that while the incidence of the many charities is increasing basically there's no effective disease modifying treatment and there are no cures. So at this point certainly as a as an audience which is intimately involved in treating the community you would have to think that this is a bit of a tragedy particularly as this is increasing and as we already know it's actually one of the top three causes of death and Australia and yet we've got no effective treatment not even really not even a symptomatic treatment. And we've got no cure at all. So this was a this was a conference just the outcome of conference the effort to develop disease modifying therapies. Alzheimer's has reached a crisis. There's been a shift in thinking about the treatment of ID away from the possibility that a single drug could ameliorate the disease. We've thought that for years. So and from a research point of view. But the drug companies are very keen to find one drug that can solve the problem because then of course you're going to prescribe it to your patients and they will make billions of dollars. Incidentally why are they so interested in making money out of it. Do you know how much it costs to get one drug to market. Anybody have a guess. Yeah it's exactly right it's about a billion dollars. Absolutely phenomenal amount of money so they quite Kane said today there is increasing recognition that the complexity of the disease the likelihood that multiple treatments will be needed at different phases of the disease. And that treatment will require more than drugs. Fantastic admission two thousand and twelve soon as I read that paper it goes straight up into my lectures because it's really important that students don't go away with the thinking that we're going to solve the world's problems by giving drugs drugs are an important element to certain phases of the disease but lifestyle particularly in one of these is going to be one of the classics I think that demonstrates that this is really the best way in which we can solve this problem. So understanding Alzheimer's Let's have a look at some of the environmental risk factors. So if we think that lifestyle might do it. What are some of the risk factors associated with developing Alzheimer's. Just before ladies you should be a little bit more concerned than the men because after the age of sixty five you're more at risk of actually developing Alzheimer's the main reasons for that but we won't go into it. So we're looking at around about close to two percent of sixty five year olds and depending on who you talk to up to a third of eight year olds and significantly more by the time you get to. Our study looking at the genetic factors and just to throw this in there again nobody has to remember all of this. But there are a number of genes that have been linked to it. Most of you would know about things like Bowie and particularly the F O E four but then there are things like personal loans in the A model of precursor protein and now a new one called trim too. These all have certain links and we don't need to go into the biochemistry there but look at how much three to five percent of the cases are actually linked significantly to developing Alzheimer's disease which means that three to five percent In other words less than five percent is genetic. What's the other ninety five percent. It's environmental it's actually your choices or yours as well as others. So less than ten percent of ID is actually genetic which means that greater than ninety percent is environmental not just being a little bit kind there. So I want to step from there so we're looking at the problem which is mostly not genetic. Vast majority is actually coming from environment. So we're interested in lifestyle medicine lost all this or all about making sure that you make the right choices in relation to your health. So we're stepping back and saying Now what are those environmental causes before I go into that I want to show you a little bit about the history of the fallen. It's another was when you take a brain of somebody who's Alzheimer's one of the key things that you see and one of these well the diagnostic marker is actually the deposition of these things called betr amyloid plaques. It's also another one called neuro Farber Larry tangles but we won't worry about that if you actually see these deposition of these and beta amyloid plaques are made up of better amyloid plaques bits of micro glia So there are some of the white cells that got things like copper and I am sitting in the middle and they actually generate lots of free radical damage oxidative stress as well. OK but importantly what else have we got this is the hippocampus hippocampus just sits in the middle of the brain and it's really important for actually coordinating memories. I like to describe it as kind of a librarian at the brain. So you go into a library at least in the old days we don't get a lot of these matching or we just call it a long line but essentially you go to the library and you say can you get this book for me and so the librarian goes off and gets the book and comes back. Well that's kind of what the campus does and Trouble is if the librarian gets tired and old then of course you go can I have this book. I've forgotten where is it. And that's a little bit like what happens in Alzheimer's because the hippocampus is one of the earliest parts of the brain to actually lose its function. Now this is the hippocampus and it's got lots of brown bits in it. That's an Alzheimer's patient there's a control. So this is the hippocampus of somebody who doesn't have Alzheimer's. Notice lots of brown bits doesn't really matter what they are except that they correspond to this thing called F. to us a prostate which is actually. Free radical damage so you hear about free radicals free radicals good free radicals a bad. OK as long as you get that. And this is actually because free radicals generate what we call oxidative stress. And where those free radicals come from I'm going to show you shortly. This is the tops of them. Told it was a little bit technical gets better from here don't worry I think. Anyway super oxide one of the biggest ones. Then you've got proxy nitrite Hodgin peroxide whole bunch of other stuff you get them mostly from generating his the MOT a contrarian. This is what generates the energy for every cell in the body and how do you generate. How does the mitochondrion get energy remember back to biochemistry. Please somebody eighty peso in making A.T.P. and you may get a pay by breaking down what sugars and fats mostly. So if you've got lots of sugars and fats. You'll get more I.D.P. right OK that's a good idea. The trouble is that you will also generate more of particularly this one super oxide. Now when you're young you get about maybe a two percent leakage of super oxide because you don't quite get all the transfer of electrons as you get older you can have that leaking out as much as ten percent now. Epidemiologically So we know that people who have lots of simple sugars and simple facts in their diet they are more at risk of disease run in the sea they're more at risk in fact of Alzheimer's one of the reasons we think that's because they certainly generate more free radicals because they putting in high calories. Yes they're getting some mighty pain but there's plenty of I.D.P. here they're actually generating lots more super oxide. Right so they are actually getting lots more of this leaking out now there's other reasons as well particularly thinking id ph oxidized. But I want to go into some of the other. But they're generating lots more of this harsher this high fats will generate more free radicals right. Then we've got these other sources for the skin years on out about it light but mostly that's not a problem for most people and then we have our antioxidants. So we want to keep them in balance. We antioxidants will protect us and these things that you will probably not heard of gluten for oxidase there's lots of them but this is a non enzymatic bits and look at this one on the bottom. These five chemicals one of them is called corrupt noids so but you know we know it's come from there. Yes and that's good because that's a sure way to safely that derive their name from you. But all the red green orange purple in fact you can go purple. My wife thinks I'm prejudiced now because I don't go for anything that's white. What cauliflower what's the point. She tells me it's cruciferous there are some sort of sulphate of molecules in there that are good for you but I will tell you later on something about current noise but just remember that that's one of their arsenal. This big package of things that help to protect us against the body producing free radicals it does just by the fact that it's functioning. But we've got to be careful that we don't get these out of balance if we do we end up with lots of free radicals and there's also the reasons why this actually ends up with him. Well decreasing your capacity to dilate the blood vessel and therefore blood pressure but we can't go into that today. So anyway I ran to tell you things you end up with increased aging disease and death and that will happen no matter what the cell type and it certainly will happen in the brain so here we're talking about the brain so that's where we'll focus. Because the why is the brain sensitive to it. Yes it's got these things called mock or glee or they just want cells in the brain that actually can produce when you switch on the immune system you actually switch on lots of free radicals. No So when you switch the immune system on you're actually making it produce lots of how the immune system will produce lots of free radicals. We also have lots of oxygen in the brain. And why do we call that oxidative stress. Because oxygen tends to be one of the primary contributors to this oxidative stress. And the reason for that is in the hippocampus remember I mentioned that was that the librarian that I am is actually very high and then you need the ion to do all sorts of cool stuff with electrons and things like that but when you've got lots of it and you've got free radicals around and you've got oxygen around you produce lots of free radicals. Yeah when you rest the brain rusting is oxidizing. Yeah I've also got these neurotransmitters So I mentioned Estelle calling but also I don't mean in serotonin and these these are all when they are broken down. They all generate free radicals. We've got lots of fatty acids in the brain who's heard of the mega three. OK good. Did you know that the brain one of the major three is called the Archer It's actually the longest one you go I lie which is what you get from vegetable sources. Then you break it down a few things. E.P.O. and D.O.J. which produce the anti inflammatory bits but the DA Cherry is the highest concentration of any of the polyunsaturated fatty acids and it's actually one of the highest. Well it is the highest fatty acid concentration within the membrane of neurons so you really need it for the brain but also if you've got free radical activity going on you can easily oxidized that and make it worse like Hadleigh is one of the antioxidants and then glue like cider toxicity which was related to that. In India I think. So these are the possible mechanisms. Now the good thing is I'm not going to go through it in detail but I just wanted to point out again ten percent generic ninety percent environmental. Now there's lots of links in here but remember this one. Systemic oxidative stress. What does that mean to stay. It's just basically the oxidative stress from the body and it's going to have an impact on the brain. A lot of work has been done on the body because it's hard to do stuff on the brain but sickly when people are alive and in fact look the really difficult thing in working in this area is that as when if people do unfortunately succumb to whatever it is even an accident something like that. The fact that oxidative damage happens immediately once the person starts to die and I stopped at what once they did it's very hard to do this type of work on anybody who's not alive because you need to preserve them. That's why most of the vast majority the work that's been done in animals we've done one of the first studies of its kind in humans. So oxidative stress in the periphery and inflammation really important blood brain barrier very quickly. Neurons never touch or blood vessels never touch the neurons. You've always got these little gleeful cells what we call metabolic support cells that actually grab on to the the blood vessel as it's going past and up to the neuron and the interface between the two and those they make a really tight what we call junctions around it's actually called the blood brain barrier. So nothing in the blood gets into the brain except it has to go through there and gets filtered. That's why the brain is very protected and it might explain a little bit later on. Anyway if this is disrupted and there's lots of ways you can disrupt it you get information in the brain free radical activity then you get this bigger amyloid clock aggregation you do get mitochondrial dysfunction and again this is not a lecture on this so I won't go into detail though be careful. There's reasons why liver time mistakes are so you taking the wrong with saturated fats trans fats will have a significant effect on inflammation we've shown that cells systemically they can impact even in the central nervous system we have an early paper from well like last year. Yeah I'll eat out a few things here but you end up with basically once you've got more of this happening. You develop senile clogs. Ultimately the neurodegeneration happens as a result of the development of that addictive neurons so this is not here to confuse anybody it's just to show that there's a bunch of stuff happening and a bunch of people are looking at all sorts of things they're looking at mitochondrial dysfunction people are looking at blood brain barrier disruption they're looking at metal designing spaces in the brain. There's a whole lot of reasons why all of those connect and they connect in ways which we can influence at an environmental level we can influence by making the right choices behavior so the details and I look at this sometimes and I watch my colleagues who are brilliant people doing all kinds of brilliant stuff and I think you know it's like we're looking at a car crash and you've had the car crash. And the person slumped over the wheel and then everybody is coming in to try and work out why did the car crash and you've got these really brilliant guys getting down there and looking at the pedal and working out how much pressure it took for that pedal to twist just like that it's going to solve what actually produced it will be about tell you what you did that how much force was needed to dent the windscreen and all that's comes up when really if we step back we can get our the driver was tired it was wit the brakes weren't so good the tires weren't so good. Basically a lot of the environmental stuff and that's what we probably need to Todd we need to be aware of this sort of stuff. And certainly we need to be aware to put it into context and there are ways in which we can do this. So even in the car crash analogy if we understand how all of those things work particularly damage to the driver It's why you can see the steering wheel it's gone through and broken the sternum and you know so which is why you can do stuff to you know have you know why they call them the airbags going off and that sort of thing. Well we need to understand this in order to be able to treat these people right. But it won't be just simply going out and going to a last hour program for a lot of people some of it will be that easy in the early stages but later on will need to be a little bit more targeted. But we shouldn't get ourselves caught up by focusing only on some of these details. OK So environmental factors these we know that age is the number one factor and as I mentioned it goes up after sixty five a little bit of stuff we published back in two thousand and ten just looking at an increase in oxidative stress we can see it significantly increase about after age sixty. We did it in animals to begin with and then we did it in humans. And interestingly enough that acceleration after about the age of sixty seems to sit about right so we're getting so much damage in the periphery can kind of pick it up or at least can absorb a lot of it. But by the time you get up to a certain level now you're actually starting to damage parts of the the body like the blood brain barrier as I mentioned which now is getting a bit leaky and letting stuff go into the central nervous system. Now the central nervous system doesn't have the same capacity to be able to deal with it as what the rest of the body does. So maybe it's more vulnerable so it may be no coincidence that the risk of developing a neuro degenerative disease begins to rise around the same time that oxidative stress appears to markedly increase in the rest of the body. It's just a hypothesis but potentially So what we need to try and do we think if this is true. That people after the age of probably sixty maybe mid fifty's. Some people we need to be more careful about what we do and their lifestyle choices simply because they are more at risk of damage they can damage themselves faster as you get older because they don't have the same resilience. So what are the lifestyle factors for Alzheimer's disease. OK low baseline follow light high saturated fat intake diabetes obesity. I almost take out obesity because. Obesity is more of an indicator at a metabolic level it's more an indicator of what people eating there are healthy obese people. Certainly they are healthy I have a wide shore it's a small percentage but I think we probably won't don't want to just focus on white control otherwise we'll be going back to things like the paleolithic diet making can confuse segments of the community which is already happening. Smoking of course we expect high midlife cholesterol low physical activity increase in these advanced glycation in products. Some of you have heard it talked of given previously that the advanced glycation in products you can get more of those from what type of foods fried foods. Yet the tasty food. No not really. But certainly the fried foods the more fried food you have the more dense Caucasian products and they do lots of stuff if you want wrinkly skin. I spent time in the sun and eat chips. It's a great way of getting it so if you're interested in aging. So the things that will reduce Alzheimer's high vitamin B three fruit and veggies in the diet. Particular people talk about Mediterranean diet high physical activity higher cognitive engagement and the high omega three S. in the cross-sectional studies are still equivocal Some say yes some say not much change. Now if you have a look at these same things in relation to there what has been known about increasing oxidative stress and I'm just trying to put these two together now. What we find is in fact the things that cause oxidative stress are the same lifestyle factors that actually cause Alzheimer's disease. So the reason why I'm putting that out there is to support the hypothesis that. And remember I said that nothing happens clinically without the first being a shift by chemically. So essentially we've got to see what is that what that makes us what's that focal point for our lifestyle. And we still might be being too. Simplistic but at least it's a place to start so that we can try and make sure so when I give you a lifestyle change and you go off and do something if I'm only just looking at this plenty of people with Alzheimer's disease that have no blood sugar control even normal cholesterol. So if I'm just looking at cholesterol and glucose I'm not going to pick up that trajectory. But maybe if I can pick up some of those damaged markers because oxidative stress produces the damage and if you are on the damage and that's often driven by the inflammatory response so I pick up some of the inflammatory markers then if I can stop that and make sure that that stop by your lifestyle change then I'll know that your lifestyle change has been effective. Does that make sense. OK it's a lifestyle factors increase the risk of Alzheimer's by driving peripheral stress that's the hypothesis so anyway very quickly we did a little study. Limited research done in humans we wanted to look at it. This is one of my Ph D. students with University of New South Wales though full time in a research institute and he looked at people across the age from nineteen twenty five to ninety years of age we took some sample for some of the sample the cerebral spinal fluid that surrounds the brain and spinal cord and we looked at some of the things we measure their oxidative inflammatory activity we looked at across the lifespan and then we look to see are there any things associated with lifestyle that might be connected to that being either increased or decreased. And we certainly found that oxidative stress increased in this case it was significantly increased over the age of forty five. Information increased with I so we got lots of stress going up and as we would have expected inflammation going up again over the age of forty five. So what were the things that were connected to it this is just a real summary of two papers we published in this area. You're not going to see any of that but essentially that's just showing an increase in what is an increase in C.S. if this is the age of the advanced glycation in products as Cox in the thigh. Last seen so basically if you want more Ages that's the type of thing that you would eat this one is an increase in some of the damage markers and you can see that this is this here is a record on I guess it and arachidonic acid is one of the breakdown products of the Amiga Six's you might have heard people talk about a mega three and the six ratio you also get lots of a record on a guess that it's a pro-inflammatory signalling molecule so you get lots of information you need is a best way to get a racquet on Cassidy's through dairy and meat. This one here is just showing that information goes up and one of the things we did observe which we didn't expect to see even one alcoholic drink a day was enough to put up the inflammatory markers. One alcoholic drink a day it's published. There you go you can quote it. But we didn't expect to see it. One alcoholic drink a day it will be great to maybe do another one just around the whole sort of alcohol hypothesis that one alcoholic drink a day is good for you. Vasculature one acknowledged doing today is good for the brain. You know you've heard of a spiritual it's not something we can do today but that would be a great one to bust and there's good reasons why we think that they do get apparent positives but for the reasons why. Now the things that we found were good and you can see that this is this is an oxidative damage product this is D.H. So one of the major stories the main one that's in the brain and you can see that significantly decreases the higher. So sorry the higher you've got to D.H.I. the low you've got a free radical damage. So why not put fish oil out there but of course if you've got a low Amiga six background then you will get nice D.H.I. from the vegetable sources. We've seen it in people though if you've got a high omega six background you can't convert your aisle either efficiently through to your E.P.A. and cherry and you've got to be really careful for that. If anybody wants to get tested. We've now set up this method we want to very few labs in Australia to do it. In fact I think one of the only we might be the only way this second one in this one in Queensland that does it as well but we've been doing it for our research and we think this is so important that we actually have now offered it to our clinicians to actually because it's one thing that you can do to at least get your patients back to at least correcting their inflammatory markers associated with inflammatory signaling from the Big Three. So at least you can get those right now there will be other things that are likely to play a role but for some people that might be all it takes. So very important and then this is the corrupt annoyed one. So again we could reduce inflammation by increasing corrupt noise so the more corrupt noise we had as we said that's where all the nice reds and oranges and greens and purples fruit and veggies and particularly there was a couple in the area of carotene beta carotene and lycopene So a lot of pain you're getting from things like watermelon and tomatoes and things like that. So if you want to damage the brain we can show you directly that this will do it even in a normal brain. If you want to protect it. This comes out and of course you know my Ph D. students not an Adventist or anything like that. This is just how the numbers worked out. It shouldn't surprise us because prophetically we've got a great foundation now while the prophetically gives us the direction to look at. We've still got to work out the details and that's what we're doing. So nine points there some foods are good for the brain some foods are apparently not good for the brain. Your choice. So what are the interactions Well here we've got lifestyle. Now there's a number of things here I'll just mention nutrition microbial burden. Certainly without dentists and having a talk with David and others. One of the ways you can actually improve the potential for Mark. Your burden in the body is to make sure that you have good oral hygiene because we know that it is some of the inflammatory activity going on and things like strip mutations and these kind of bugs that are growing around the teeth can end up systemically creating an inflammatory activity which actually produces some vascular damage and that can be heart disease but it can also contribute we think significantly to that continual degradation and damage occurring within the brain. Exercise we know about alcohol. Now we're not suggesting you increase alcohol there that is these are the bad things you know not enough wrist high saturated fat low nutrient foods I'll just mention rest just one quick quick thing here. You're aware that those in the health care professions are actually the highest you have a higher risk of lifestyle associated disease than the rest of the population and one of the trenches he says is that it's the wrist component. You know you really get kicked out in terms of the bi rhythms and you don't give the body enough time to rest and repair and the biochemistry in the morning what's actually switched on to do stuff in the morning is different to what happens after about three o'clock in the afternoon the body starts switching off different things. And since this factory up for going we need to rest and we need to get some maintenance. But you're going to give me some caffeine. I'm staying up for another few hours. Tragic you know anybody who runs a factory like that I'm going to get more output for probably about a couple weeks and then of course the factories going to Deilmann isn't and they going to be down for weeks in order to get expensive repairs done hormone imbalances vitamin D. psychosocial stress sleep apnea. So there are a few things that that will contribute some of the major things we think we will we certainly know that I will increase free radical activity in the body largely driven by that inflammatory process can also happen in the brain but the important thing is that there is a significant link between what's happening in the rest of the body and ultimately the contribution it's making to the brain more. That happening within the brain neuronal dysfunction and you certainly can develop neuronal dysfunction before you end up with neuronal death. That's important because we want to be able to bring it back. Now if once the neurons have died they're not coming back. But if we can get it early you can then preserve that neuronal function and we all know that neurons generally aren't going to regenerate. So in your generation which is cell death and of course you can your own dysfunction contributing through to that the Matrix well so that is the background. If lifestyle shifts the biochemistry towards disease and would you agree that that's possible. Lifestyle is concerned certainly with an audience like this lifestyle can shift you towards disease and we all know that you don't develop Alzheimer's or the not so if you don't develop any of the county vascular disease or not. All stroke so ultimately this is a trajectory that this person this patient potentially yourselves have been on for some time. At some point you've diverge from health you can either go this way and maintain yourself up to probably one hundred ten years of age or you can go this way and die of some kind of lost all associated disease. A lot of the and we know that eighty five to ninety percent of the population will die of a lifestyle such a disease in this country. I just want to show you this one. This was published in September of this year. Reversal of cognitive decline a novel therapeutic program he took nine Alzheimer's or ten Alzheimer's disease patients nine of them he got some great results using a multimodal intervention displayed a significant improvement in cognition after three to six years now wasn't reversing them back to the thirty's but got significant improvement what do they do and the results were maintained after two point five years. So the key elements. OK forget about all of that basically made them fast making sure they had a twelve hour fast overnight and that day I eat three hours. Or going to bed. So in other words it means that they finish their dinner by six. They're in bed by nine. They got up and had breakfast at six easy today. Sounds like either way I think. Perfect. Yeah I wish we could do it here. I wish we could do it here. So that was the first thing they optimize the diet and the key thing that I did there was reduce their simple sugars. Basically I took them right out and said If you want to get better. No simple sugars for you. So no desserts No well I can have desserts but no refined sugars associated with that and we know that that significantly impacts oxidative stress and inflammation particular without people reduce their personalized stress So in other words they are able to that should be a down arrow. It actually reduce their Hypertime churchy adrenal axis that stress response which we know drives up certain hormones which have impacts on things like cortisol and a whole host of other which actually drive a lot of oxalate infantry activity as well. Oxidative activity it suppresses some of the immune system but. They optimize this slate so that they got at least add astronaut. They gave the melatonin. Now I want to go into all of this you can buy melatonin over the counter in the US which I think is a great thing. In Australia you need to get it on prescription but you guys can all prescribe it. The not to say of course but point five milligrams Now that's quite a lot and for an old person that's probably OK for a younger person you would want to have significantly less. A younger person is probably going to produce bound about point one if you get to bed by nine o'clock you will get your melatonin pick the longer you stay awake the lower your melatonin pick. So anyway I supplemented their they gave them trip defend there's a reason for that trip the fan actually produces both serotonin and it also produces. It's significant molecule called an ID which we know is associated with driving what's called the longevity enzymes. Complicated business trip to fan is one of the least abundant amount of acids in the body and they made sure that I had enough of it. They made sure they could exclude sleep apnea so any problems with their breathing they made sure they could get rid of it simply because you have these intermittent anoxic events so I don't even know what I'm supposed to finish. Now probably I won't tell you that story but you know you really need to make sure that sleep apnea is not an issue. They exercise them thirty six to thirty sixty minutes per day four days a week. That's pretty straightforward gave them little exercises to do for their brain make sure they had plenty of vitamin D three and why K two Does anybody know what K two vitamin K. to. It keeps the Cascine and I'm glad there's at least one person who knew because this is one of the critical things you often see patients going on calcium supplements and then wondering one is a type of it was actually just published just well just this last week showing that those on calcium supplements had greater risk of developing vascular associated dementia and the reason for that was is that they found the calcium deposits in the small blood vessels in the brain associated with some of those so they're actually getting a little bit of that vascular in fox in the brain and therefore getting some leakage because they probably had lower K two and yet they're on calcium supplements so they're actually ending up with and with an oxidative stress background you actually end up with calcium deposition and you actually turn your little into failure cells into buying. Not great so see the Colleen that's just fast Alcala and then you've got the R. CHENEY Ph R.M.A. three. They gave them as virtual. We think there's better ways of doing it but in any case they got great results nine out of ten increased in fact three of the patients who had left work. Which are fairly young Alzheimer's three of them were able to go back to work and were able to function normally at work. We actually have a grant very similar to this that we've just developed to put in we're going to do it slightly differently to this end. But there are some key elements that are similar to them both and very excited about it and what's really fascinating this is the first study of its kind. Now it would be the second one. And what is fascinating is that from that perspective the reason why we even came up with it is because of course we were looking in the right direction. It's not that we're geniuses sitting there it's just that on the basis of what we've been given as a platform for health it made sense to look in this direction and all the biochemistry seems to fit in with that. When we presented that to some of our colleagues at one of the other big brain research institutes in Sydney that I jumped all over it because I would have to be involved with that this is what we should be doing. This just looks great this is how we we can do your imaging in this. On testing and that is because we were looking I think by God's grace in the right direction. So but poor lifestyle choices don't affect don't just affect the brain of course this is just to cap it off. We know the top three heart disease we got twenty thousand deaths forty percent of all the strokes. And look they're not unrelated. Around nearly eleven thousand and then the nature under it at ten thousand and one is fascinating and a discussion for another time maybe around a lot more sort of technical elements but this is just showing the blood vessels within the body. A lot of what you do particularly and we publish this little paper I don't think it's a particularly brilliant paper for some reasons but but it was the right kind of action where we actually did the ice cream study some of you heard me talk about it and we actually showed that you got an increase in oxidative damage within the book. Their souls. So within the blood within two to four hours after having a meal which was high in fat and high sugar. Now notice where the blood vessels what they service. Massive amount up in the brain. But of course the kidneys and the lungs of course and then everywhere else in the body and if you don't look after that bit then a lot of the other bits aren't going to be serviced will ya. Cancers actually come in. Number four I think now it just depends. Mostly the the long talk just depends on how you add the numbers up but you know your top five are all going to be the same car that struck all of these cancers of various types and then part of those are at least Alzheimer's stroke and heart disease. So the link there lost all driven oxidative damage to blood vessels my underpin the connection to multiple diseases which I think there's a growing consensus certainly in the research community on that. So where is the final and this is the second last slide. Essentially if physical Well when young for the majority the population depending on how you treat yourself the high kilojoules diets nutrient poor or low physical activity poor sleep etc They'll be the subclinical oxidative planetary activity going on the bodies trying desperately to look after you but it's having to work real hard so things start getting damaged. Chronic tissue insult over years but this or small organ systems may be the first thing you have is it's probably you know diabetes or something early on cardiovascular disease coming in situ accelerated damage then occurring within the brain this is all caring sort of around middle age. Then we get reduced tissue oxidation resilience accelerated tissue damage now caring in the brain degeneration of multiple organ systems we know. No you know significant problems with kidneys and liver and cetera neurodegeneration adventure occurring in the older age group. The key thing is to assess and treat largely around lifestyle. When young and if you can get that culturally then you're really on a winner. And look at this with the health department for New South Wales or better still the federal government. I would give almost exactly the same talk because basically that's what you want to change and you want to get that affected here unless you want to spend billions on your health budget unnecessarily and then assess and treat last August and here is probably the last chance. It's not the best if you look after yourself here then you've got to be looked after way up here. But at least this is probably your last goodbye leave a little little bit too much longer and there's going to be unfortunately not enough healthy tissue around to be able to work with. So if I start by chemistry towards disease then changing our style should be remedial that makes sense and the question is is lost on that is an important part of not only you can Bill Press and I would give the same talk regardless whether I was talking to a community G.P. network. I've given some similar things not exactly this. I probably would leave this one out. Sorry it's important part of your own life I would leave that one in but I will probably leave this one out this is iti want spiritual gifts those who bring disease upon themselves by self gratification have not healthy bodies and minds. They cannot weigh the evidence of truth and comprehend the requirements of God This applies to us as much as it applies to anybody that we are serving our Saviour will not reach isn't low enough to raise such from a degraded state while state persisting whilst I persist in pursuing a course to sink themselves to all they are required to do so all are required to do what they can to preserve healthy bodies and soul and minds and sound minds and I think if I can leave it. Air because if you every one of you in your clinical practice in clinical specialty if you adopt a great lifestyle practices which is going to help yourself then you'll be much more credible and also much more knowledgeable to be able to give that to your patients. I still think as a group we probably need to get the facilities right so that we can network well so that we actually genuinely have some you know centers we can refer to centers of excellence for lifestyle medicine and that type of thing. Very happy to hear the discussion of this media was brought to you by Adil purse a website dedicated to spreading God's word through free sermon audio and much more if you would like to know more about our universe or if you would like to listen to more sermon Please Visit W W W dot audio Verse dot org.

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