Stephen Cunnane - Can Ketones Slow Down Alzheimer’s?

[Music] this lecture is being brought to you in part by the generous gifts of these sponsors Thank You Bonnie and thank you all wow what a crowd this is really a pleasure and an honor to come here and speak to you tonight met Ken for a couple of years ago and I greatly respect his personal story and also the type of work that you're doing here at IHMC so it's a pleasure to come here and talk to you a little bit about what we're trying to do in this important field and I'm sure that many of you by the color of your hair are thinking quite seriously about this question that that's on the screen so let me start by saying that this is what the view from my living room window is like it's not quite Florida but it's cold up there now and it's a wonderful place to do winter sports if that's your thing let me show you where we are in relation to you I chose this form of projection of the map of North America so Canada would look even bigger then but it's mostly empty up here and I don't know what the distance is exactly but we're up here north of Boston about four hour drive north of Boston out a little east of Montreal so that's where Sherbrooke is and and who would want to go to Sherbrooke out in this sort of countryside a bit like Ocala in relation to Orlando I imagine it's because they do very good imaging research in Sherbrooke and because they have an excellent Research Center on Aging and my personal life brought me back into Quebec where I actually grew up but the first part of my career wasn't there I want to start by making my disclosures we have funding from the public sector government agencies like the Alzheimer's Association here in the USA and Canadian agencies of various sorts and the private sector funding as well which has helped us do some of the work we're doing so I've got lots of conflicts of interest I think we all have conflicts of interest we all have commitments and beliefs in certain ideas and I hope that my support from these organisations is not colored the way we see this story I think every story needs a beginning and I think it's important to start with some of the pioneers in this field John Freeman died recently has anyone heard of John Freeman so John Freeman as I may have mentioned here was responsible in a big way for reviving the ketogenic diet for intractable epilepsy particularly in children George Cahill also was a pioneer in this field and died recently as well he was the one that really put ketones on the map because they'd known for a long time that something was helping run the brain besides glucose but no one really knew what it was until the late 60s when he did some fairly radical experiments that we probably wouldn't be able to do today but we've done them and we've benefited a lot from the work that they did I don't know when but Veatch was born but he's still alive and he's doing some excellent work on this area as well he was a student of hands krebs from the krebs cycle part of part of the the cellular machinery that generates energy and so he's an important player and has been a very active and vocal in this area and helping give ketones some solid scientific credibility this is a name you might not recognize me a kivi belt oh but she is a pioneer as well she's younger than these old farts that are higher up she's a Finnish lady neurologist and she ran the finger trial so if you google finger or finger trial would be better because you might learn about other fingers besides this trial you'll find that this is the main in my view and I'm going to finish the talk referring to this trial I think it's the most impressive prevention type trial to slow down cognitive decline in older people it's not on Alzheimer's disease but it shows that a concerted multi-pronged approach to prevention can be beneficial and I'd like that's my take-home message and we'll come to that towards the end so let's look at the brain and it's this story is about brain energy metabolism it's about brain fuel and this is a simple cartoon to try and give you an impression that the brain is kind of like a hybrid car the brain is running not on electricity and gasoline but on glucose and ketones and it's keeping that process running properly that is a challenge as we get older it's a challenge to get the main fuel which is by far glucose into the brain and it's a challenge making the switch because if you're in good health then your body is making that switch all the time but people who are at risk of Alzheimer's because of type-2 diabetes insulin is a bad guy in that situation an insulin is blocking part of this process a point that I hope to get to as well so try and keep in mind that what we're talking about is fuel and we're talking about a hybrid brain that's running on these two fuels I'm not a chemist but I'm gonna have to show you just a little bit of chemistry very simple to identify these molecules when we talk about ketones we're talking about ketone bodies which is the old term shorten it to ketones that are generally dry not exclusively but generally are coming from our dietary fats or our stored fats and the first one that the body makes when they are being produced primarily in the liver is this molecule call acetoacetate and it is in this two-way arrow means that it's in a balance with the one you can measure with these finger prick tests that you can do with certain devices and this is beta-hydroxybutyrate just a small chemical difference between the two and there's some degradation of acetoacetate to acetone which is the same molecule as a nail-polish remover your body's actually producing the same molecule and in relatively high concentrations about the same concentration so this is not a negligible product so these are the main ketones there are some others that that but they're not really relevant to our story so what I want to do is give you three for me guiding principles around ketone biology in the brain the first one is this thing that I call a push-pull story because there are two strategies to get energy into the brain this tube here on the left is the blood and this rectangle on the right represents the brain and this little stick person here in the middle is pulling glucose into the brain it's the pole part and and why is it working that way it's because that he's activated or she is activated by the fact that glucose will go down when that cell is done something it's talking to its neighbor and so when the glucose goes down in the blood the transporter is activated and a molecule or several molecules of glucose are pulled into the brain if this cell is not very active then this process doesn't happen and that's normal that's fine but it's the opposite to what happens with ketones ketones don't care how busy this cell is when the ketones go up in the blood they are pushed into the brain they are the backup fuel for brain and that's an important mechanism because if glucose starts to go down because you've been fasting you may have been sick for a few days or something like this there's less glucose available to do this ketones will start to go up and they need to get into the brain quickly so they don't hang around for a signal from the brain they are pushed in right away and so they're the two fuels are quite differently managed in the body and and the advantage for us is that we can provide more ketones and we can be pretty sure they're gonna get in to the brain at least into the normal brain we'll come to the Alzheimer brain in a minute the problem of partly to is related to glucose no I'll leave that point to later so that that's the first point there are two strategies we have two major fuels in the brain and there are two very distinct ways on which they get into the brain one gets pushed in and the other gets pulled in the second point is that this is a concocted image actually of a fetus with that's actually a human brain that's been projected into the head of this infant but I think it's a dramatic image to remind me to tell you that ketones are helping run the infant brain all the time they're not the only fuel that goes into the brain but the infant's brain is very large compared to its body as you can see from this image much larger than ours as adults and this brain absolutely depends on ketones day-in day-out it's not a question of being sick and there's not enough glucose and Oh ho-hum we'll use some ketones it's it's an essential part of that baby's growth and development every single day and where do the ketones come from a little bit from the fat and this is a pretty skinny baby but mostly from what source do you do you know what source where the babies get ketones from from the milk from the medium chain fatty acids in the milk and there's lots of medium chain fatty acids in the milk so when we talk about potentially using ketones to rescue brain function in older people what we're trying to do is basically recapitulate the situation in a normal healthy baby this is not a baby that has a disease or that's been stressed or that's fasting this is it's normal healthy development so we're just trying to recapitulate physiology of the baby in an older person and the third point in this context which make might look a little challenging to understand at first is that ketones are the brain's preferred fuel and I underlined it because that's what I'm really mean they're not the main fuel in the brain but they are the preferred fuel how do we know that if we put people into nutritional ketosis so if you start taking a ketogenic diet today four days later we did these analyses and we showed this this term down here means this x-axis means that it's the change in ketone uptake by the brain the Delta means the change and your numbers have all got a plus on them so they've gone up from what they were before the ketogenic diet to afterwards and this is called an inverse relationship which means when this number goes up this numbers going down it goes from minus minus five down to about minus ten so the glucose is here on the y axis and the glucose uptake goes down in direct relation to the amount of ketones that are available that might seem counterintuitive but in fact the brain only needs so much energy and if it's got a choice between ketones and glucose in a young healthy adults it's going to choose the ketones and hold back on the glucose so we want to exploit that and that means you conserving the glucose for other things that glucose can do besides simply fuel the brain so this is an important concept there's not a lot of ketones in the blood we can push that up but when they are available they're actually the preferred fuel and I'm going to come back to this point at the end because it has relevance to to Alzheimer's so let's talk about this story of brain fuel in Alzheimer's disease what is the problem these are called pet images PET scans and the control brain looks typically like this where you have the areas that are really using a lot of glucose or on the red to orange color and the areas that are not using any are in the blue so it's a rainbow of colors the blue areas are blue because those are the ventricles they contain liquid they don't contain any cells so they don't use any glucose so that's a normal PET scan the problem we've known about for nearly 40 years now since the dawn of PET scans in the late 70s is that to areas where these arrows are which are called the parietal lobes over the ears are not using glucose very effectively so we call this brain glucose hypo metabolism hypo meaning lower than normal this is a signature of Alzheimer's disease it's not a diagnostic tool but it's almost always observed so the question is how the cells died there and they're not using glucose or there are the cells actually alive but they're not able to get or utilize the glucose very effectively is it the cart or is it the horse obviously if they died then the ability to use glucose has got to go down so we started to look at this and our concept is that the brain energy deficit precedes the cognitive decline in people that don't have Alzheimer's but are at increased risk of Alzheimer's the yellow box refers to these people who are at increased risk who have lower brain glucose uptake it's called latent pre-symptomatic brain glucose hypometabolism that's an earful it's latent because it's very low key it pre-symptomatic because there's no cognitive symptoms in these individuals no symptoms of cognitive deficit who are they older people me me included lower brain glucose uptake people with insulin resistance it's not just older people I'll show you an example people with a family history of Alzheimer's disease people that are carriers of what's called the e4 allele of April lipoprotein II and the priests million carriers who are the by far at the highest risk they are basically guaranteed to get Alzheimer's because of the mutation they have in each case these are people that have been studied before they have any cognitive symptoms and guess what they all have this pattern of glucose hyper metabolism it varies from one of these conditions to the other but they all have a problem with energy before they get to the disease so let's put this into context they've got some problem with glucose weakens our concept it's our concept this is helping contribute to the problems in the brain the deterioration of the synapses because the brain is running on 10 to 15 percent less fuel and it should be getting it's like trying to run your car on three cylinders instead of four it's not gonna work very well and this in turn leads to the cognitive decline and eventually some of those cells are gonna die and the glucose uptake is going to go down and we develop a vicious cycle of brain energy exhaustion and progression of the disease now this is just an idea it's a concept and if I go to the Alzheimer Congress as I did last summer there's almost nobody who's going to agree with this so you can put a concept up before people or you can test it and one thing you can do is test what is happening to other fuels like ketones if those cells are dead they won't be able to use ketones right so let's look at that idea again either the brain cell is not able to use glucose or it's dying so this is my imaginary brain cell both situations have low glucose uptake but if the cell is dying it won't be able to use ketones either would you agree if it's starving we'd be able to see it should be able to use ketones if you are hungry and your body will be using ketones in your brain a person can starve for over 30 days and the brain will be running predominantly on ketones so the fact that you've been starving was not going to prevent the brain from using ketones that's for sure so if you've got a PET scanner for the glucose studies this part of it you need to be able to do the same measurements with ketones and that's what we developed in our Center in in Sherbrooke so we looked at these types of scans and we compared them in people that are we're at risk of Alzheimer's or with Alzheimer's disease and then we compared them to the ketones and this is an overview of the results we saw so brain glucose and ketone uptake in Alzheimer's disease and in mild cognitive impairment so mild cognitive impairment is MCI and Alzheimer's is abbreviated as ad do you see a difference in the colors from the top to the middle to the bottom maybe the people in the front shout out what you see do you see more green at the bottom or more red there's more green at the bottom and what does this scale show you maybe you don't see the scale very well but green is towards the bottom of the scale and red is towards the top so that means that the Alzheimer brain is using less glucose okay we're not the first people to show that so I showed you a slide of that earlier it was a cross-section of the brain this is a what we call a surface projection but this is confirming that our PET scans and our people with Alzheimer's unfortunately have what you would expect to see a problem getting glucose into the brain so what do you see on this other side it's the ketone story there's green here but there's a little less green here a bit of yellow and these are even a bit of orange and perhaps a reddish color at the bottom that means that the Alzheimer brain is actually taking up ketones better than the control brain and these are age-matched individuals men and women so there's no problem getting ketones into the brain and there is a problem getting glucose into the brain now these people were not on a ketogenic diet they weren't on a ketogenic supplement they weren't on a ketone salt or any of the ways you can supplement your ketone they weren't fasting so the question became well let's just summarize that result first of all to come back to our example if the cell was dying then the ketone uptake would not be normal but it is so we can initially at least eliminate this question of is the brain cell dying is the glucose uptake problem due to the cell being dead no because ketones are getting in normally so this gives us a chance to explore a therapeutic effect of ketones the question then for us was can the Alzheimer brain use more ketones when they're available in larger amounts because if we go back quickly to this image this is under normal circumstances your brain is using one two maybe three percent of its energy is coming from ketones this is very low levels if we're trying to correct this problem with glucose which is on the order of 15 to 20 percent we're getting being able to get more we need to get more ketones into the brain and this slide shows in a kind of a graphical way that when you raise plasma ketones in people with Alzheimer's disease plasma ketones have gone up from 0.4 to 0.8 on our treatment the brain ketone uptake is shown on the y-axis and this faint dotted line in the background is our healthy young controls this is the relationship that would be the ideal situation and where do these two lines fit this is called the pre point that means before they've started a ketogenic supplement the post is after they started the ketogenic supplement we've only got data for seven in one of our medium-chain triglyceride supplements and eleven for the other but these two lines are stuck to the to the reference line so the bottom line is that when you provide more ketones to the Alzheimer brain it can use them which is neat this is this is what it's all about for us if that line wandered off here somewhere it would suggest that you you raise those ketones like crazy in the blood but the brains not able to use them so far so good let's look at what happens before you get Alzheimer's disease that's the condition called mild cognitive impairment and looking at people that have been on a 30 gram per day medium chain triglyceride supplement this time for six months so this is a study that we not only had a long relatively long period of time we also had a placebo involved because now we're getting to think that we've got a chance to do something interesting here we've got to do this right we've got to compare it to a placebo there's quite a placebo effect in treating people with memory deficits and and cognitive problems as they get older when we look at the brain what's happening to the ketone uptake it's similar whether they're on the placebo or on the end before they start pre is before they start the placebo or the MCT treatment doesn't change after they took the placebo the two blue bars are obviously the same but it's doubled on the MCT so this again shows that the mild cognitive obviously if people with Alzheimer's can use ketones normally we would have expected this to be the case in an MCI and mild cognitive impairment and and we have these data and we've got twice as many people there's 19 people per group so our data are a little more robust right now and if we come back to that slope line we've collected a lot of data over the years now not all of it being ours in fact some of these data out here at very high plasma ketones were people who were starving for 60 days these are published results they all survived by the way they were in medically supervised weight loss fasting for weight loss but the point is the relationship between the plasma ketones and the brain ketones follows this line whether you've got very low levels of ketones or very high levels it's a very straight line it never seems to hit the ceiling the capacity of the brain to take extract ketones from the blood it's phenomenal and our mci are exactly on the same slope the line is offset the blue line is offset a little bit because we measure acetoacetate and these are our measures of beta-hydroxybutyrate and the uptake is not identical in the brain but what matters is the slope is the same so it shows that if the issue is to get a little more in all we need to do is raise the plasma level a little bit more and that's was a very encouraging result for us to see so let's say you are working for the regulatory agencies what's the regulatory agency here in the US called the FDA and you've got a new ketone product that you would like to be able to get approved for cognitive issues pretend you're wearing you you've got responsibility to FDA for making this decision so I think the question you're going to ask is who cares about whether ketones are getting into the brain that's not the bottom line the bottom line is well I care too but the bottom line is does it solve a memory problem or not correct that that's my point I'm being a little bit facetious and so what we need to do is look at some of these tests that people do and maybe this is not as big as as it should be but there are tests of what's called episodic memory there are tests of executive function processing speed working memory attention and so on language and we've administered this battery of tests in the study that I just referred to and the results generally speaking look like this the MCT being the active treatment and an upward facing arrow is a positive outcome the yellow is a negative outcome and there are some positive modest positive effects even in the placebo group so we've done an important battery of tests and we've looked at people with MCI six months on the MCT and we're seeing some trends that are interesting if the next and critical step is to you probably can't see it at the bottom unless you're up at the front here but the next step is to expand the sample size because I showed you the results for 19 people well 19 people in the placebo group and 19 people that complete this study in fact we recruited 54 people that's a $750,000 study to do over three years that's a lot of money and we appreciate the investment but all we could study was 19 people that actually finished the treatment so these are trends some of which are significant with the with the bigger fatter arrows but a neurocognitive specialist would look at data and say well you've got a statistical difference with 19 people but it's not enough so we're going to try to do a larger study now and this is called a proof of principle study we've got some very encouraging results but they're not definitive that's not going to stop any of you that wish to using MCT at home if you choose to they're approved by the FDA and our FDA in Canada is called Health Canada you can buy them as I'm sure many of you know off the internet or at your local health food shop and you can experiment with them safely and with some hope that you might see some beneficial effect I'm not selling any product here but I'm telling you that this is enough - you could wait five more years some of you might not have five years to wait so you've got nothing much to lose to give this a try another thing that you're going to do as as the FDA representative handling this file is to say who else has done work in this area who else has found something interesting they call it external validity is there something weird going on in Sherbrooke Canada that doesn't happen anywhere else well it's a fair question so has anyone else seen the same beneficial effective key tones on memory in older people and the answer is yes the ketogenic diet has been used in a couple of studies Robert Krekorian used it and published the data in not in 2012 in a randomized controlled trial I think he finished with 12 or 14 people per group so an even smaller study than ours Russell Swerdlow has a paper that is actually just on on PubMed now I think that was just published with I think it's 15 people no placebo group so it's not a randomized trial it's simply ketogenic diet how many people have tried a ketogenic diet I see maybe 20-30 hands go up so you know that that's the challenge is to change in your lifestyle completely right he had these people stay on it for three months it also took him five years to get 15 people to complete the study so it might be an excellent solution but is it a practical solution we don't know Suzanne craft is doing work on this right now and I haven't seen any progress reports from her group Sam Henderson working for a company called axe Sarah published a paper nearly 10 years ago now which was a randomized control trial as well with a modestly interesting effect of the MCT called caprylic acid or c8 he then tried to reproduce it and and was not successful and we have a work a work in progress so one of the questions is I think that there's it's clear that we can get more ketones into the brain if we try so it could mean that you can get all the ketones into the brain you want to but the effect on memory is not so simple even though we see what you call a straight-line relationship with some cognitive scores so it could be that you might get some improvement but it's never going to get much better or it could be that it depends on how much ketones you get in how men out of ketones did you get in the dose in other words of your ketogenic product so I've got a little bar graph to show you that gives a little bit of an idea of what what I mean in the sense that over here on the left are cognitively normal young people and the the dotted line here at the top is 100% so what is their brain running on it's running 97% on glucose and 3% on ketones approximately you're cognitively normal older person is whoops got a 7% deficit here not in ketone uptake but if glucose levels have gone down the uptake of glucose has gone down by 7% it's still cognitively normal the person with mild cognitive impairment not taking any supplement it's gone down a little further eight nine percent ketone uptakes still normal the person with mild cognitive impairment like in our six months study taking 30 grams a day whoops we've got more ketones we've increased the yellow bar quite significantly but we've still got a deficit 30 grams a day does not replace the glucose that's not getting into the brain so over here on the right we've calculated that we think it would take at least 45 grams a day in order to meet the brain's energy requirements and bring it back in terms of energy to that of a younger adult so that is the brain energy gap the young person doesn't have a brain energy gap but as we get older we all have a brain energy gap and some of us can fill that gap with ketones if we take a ketogenic product so that's the work we've done with Alzheimer's disease and with mild cognitive impairment we're still at what you would call the proof of principle stage and we're pretty encouraged but we've got a long way to go still one of the things that's important to think about is to come back to this balance and I was about to tell you at the beginning about insulin and I decided to wait until till now because one of the main factors for Alzheimer's disease as we get older is type 2 diabetes and what is type 2 diabetes basically to boil it down it's because we're not very active and it's because insulin is not doing its job very well insulin is trying to get glucose out of the blood but it's not able to because you've eating every day and a fair amount of refined sugar and insulin is trying and trying but it's getting tired and it's not working and it's there and in pancreas is pumping out more but it's not working very well and I mentioned in one of my my conceptual vicious cycle slide that people with insulin resistance have got a problem getting glucose into the brain well the problem with insulin is that it screws up the glucose entry into the brain but it also prevents the ketones from getting into the brain prevents the body the body's fat tissue from releasing the fatty acids that are used to make ketones now you've probably confused medium-chain triglyceride that you take as a supplement is going to make ketones and insulins not involved but if you fast or if you're on a ketogenic diet the ketones are coming from your fat stores and insulin is blocking that so basically insulin puts the brain in double jeopardy because it's two main fuels are now not getting in properly well insulin resistance is not just something that happens in older people here's an example of young women 24 years old with a form of insulin resistance due to polycystic ovary syndrome they're 24 years old and these patterns of color here are the areas where the brain is not using glucose properly one of them is this big red area which is the frontal cortex where they have at least a 10% deficit the green and blue are the temporal and parietal cortex parts of them where there's about a 10% deficit as well this is strikingly like what you see in someone 65 years old but they're 24 years old and so insulin resistance is not just a function of aging it's affecting the way in the brain is using fuel independently of age so we've got to try and reduce in some resistance if you think prevention you've got to take care of insulin resistance you've got to make insulin work better and one of the approaches that I think was successful in this regard is the kivi belt oh study that I referred to the title in the paper was a two year multi domain intervention of diet exercise cognitive training and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people a randomized control trial so they're at risk but they don't have Alzheimer's disease it's a randomized control trial how do you randomize and what you can randomize but how do you control for diet exercise cognitive training and vascular risk reduction that's a big challenge but it can be done they give them standard of care which is try to eat a better diet versus this is exactly what you should do because telling someone to eat a better diet is gonna go in one ear and out the other if they're in a randomized control trial well you don't want them eating a much better diet because then they're gonna be doing like the active group but this is a very challenging project they had 1,200 people complete this trial 600 on the active arm and 600 on the inactive Ironman just to remind you of what these interventions were physical activity three times a week the cardio badet metabolic risk reduction is basically get the insulin down the cognitive and social stimulation was done together so people were learning how to use computers and people were doing things together socially but cognitively as well playing bridge for instance is Co social and it's cognitive at the same time better nutrition was personalized they made measurements of the vitamin status the omega-3 status and they said well this person needs more omega-3 they get a supplement this person doesn't they don't need to this is a complex approach it worked actually the placebo group improved somewhat but the active group improved even more so this showed 91% of the people that started this study completed it and it's a two-year intervention most of the time the the the the gurus in the field said ah prevention doesn't work and even if it does nobody's gonna do it well that's not true because this shows that it can be done and what we want to do in Sherbrooke is add this red bar at the bottom which you can hardly see but to add a ketogenic supplement because the one thing I think they didn't do is provide a better supply of brain fuel you can reduce insulin resistance which is a great thing to do but that doesn't get more glucose into the brain that problem doesn't seem to go away and the only way I think we're going to get more fuel into people is to get more ketones in and we're gonna call it keto finger we just need 10 million dollars but apart from that we're ready to go where is that we're at the starting line ready to go and you know the neat thing I didn't mention it but the neat thing about physical activity we've done a study of the brain ketone and glucose uptake physical activity in Alzheimer's disease increases brain ketone uptake so if we give them a little MCT or some other ketogenic supplement plus the exercise we have a better chance of getting the ketones in that we will with either one alone and that's part of the recipe this is an essential recipe to to improve your chances of staying cognitively healthy longer in life so I will finish by saying thank you and as the British say if you've been on the London subway the tube mind the gap thank you how do we do Thank You Steven we have time about 15 minutes for some questions so Christy's got a mic back there wait for the mic please dr. Canaan my wife was diagnosed 10 years ago with mild cognitive impairment two years later that diagnosis was upgraded to a D her neurologist or her own access product which as long as it was available seemed to work quite well but six months ago at the trial failed and it's not been available since then we've been using ketone salts started that thirty thirteen grams today we've upgraded it to twenty-six along with four tablespoons of a day of coconut oil and that seems to really be doing the trick if there's something more we should add tell me about it please well congratulations first of all because that sounds like you sounds like you're helping to slow down the progression which is all I was asking in my title is can we slow it down I think you've given us an example that maybe we can I would encourage you ma'am to try and do a little exercise I'm sure you're thinking about that I think it's going to help make those ketones whatever dose you can take it's going to make it more effective try and stay in your social clubs your social activities as much as possible gets that stimulation get the brain cells talking to each other and good luck I don't know who's one of the things I've been looking into is certain things related to anti-aging and as well as good health and one of the things I've read about is the drug metformin which people with pre-diabetes are taking and also it appears that people who do have diabetes that take it may live longer than people who don't take the drug so I'm curious about alternate ways of solving the ad I think you're it's a great idea because what metformin is helping do is make insulin function better helping get rid of some of the glucose that's present if you do a search have you heard of PubMed you know that this is the way people look for scientific articles I was a little alarmed when I looked at when I did a search on Alzheimer's disease in metformin there are some positive results but they're not all positive so I'm not here to be alarmist but I'm not sure that metformin is part of the solution there may be some pharmaceuticals that are going to be helpful and I'm don't want to worry you but I I think you need to talk it through with your physician I'm not here to give personal advice for sure maybe metformin is part of the solution in your case and but maybe not it's something we need to find out I think if you can use exercise it's gonna it's gonna help regularize insulin as well and that's what what we should do as much as possible a few years ago my MC sponsored a talk by dr. Newport I think her name was and she reported on a study she had done it's anecdotal at Vaska she only had one patient and that was her husband and the she started him on some serious doses of medium chain triglycerides with remarkable results and I was just wondering if you know who she is or know of her study and what the update on her husband's status is well I do know marry know Newports moderately well and I'm quite familiar with her the case of her husband and I say it's it's a case report she had a combination at various times of coconut oil or plus or minus in MCT with the ketone ester that was developed by Bud Veatch at the NIH and there was phases when he was on a drug treatment that was under development at the time so I'm not sure what to make of it was coconut oil actually beneficial if coconut oil is beneficial in Alzheimer's disease and I'm not saying it isn't yeah I think each person is going to find out nobody's done a controlled clinical trial so we don't know what we do know is that coconut oil does not change your ketone levels I'm going to repeat that because I'm sure it's gonna surprise some of you but in our experience short-term studies ketones do not go up because the active part that makes the ketones is particularly the 8 carbon fatty acid called caprylic acid c8 and there's only about 5% of coconut oil is c8 roughly so there's no way that it's going to be very active in terms of making ketones that doesn't mean it's not doing anything for the brain and so I the jury's out on that is anyone gonna invest in doing a control clinical trial of coconut oil I hope so but that's that's really the issue because these studies are expensive and until we can really assess them with it against the placebo you don't know yeah my question is then what would you recommend for us as a diet or and whether ketones come in a form of some tablets or how do we get it well in terms of your general diet try to reduce the refined sugar as much as you can take the pressure off insulin go out and walk if you don't like walking swim find some way to be active but well that's as far as trying to keep insulin happy because you're trying to reduce your refined sugar if you still insist on having a piece of chocolate cake at supper go and work it off afterwards by taking a walk there are various ketone supplements and assuming that what's on the label is really what's in them and that's not always the case then gram for gram they're probably pretty similar broadly speaking so if you prefer to take a salt in a packet and put it in your coffee that's fine if you prefer to have it in a liquid in a milkshake and you don't what you want something that's cheaper then you can take an MCT if it's got c8 in it it's going to be ketogenic there are some c8 products out there sorry I I don't know who has the mic but I got a blip from a friend of mine when she found out I was coming here today and she said that on the news the Cleveland Clinic is working on a drug that may reverse Alzheimer's and that it's been successful in animal trials have you heard anything about that No you know there's lots of people working on on animal studies of Alzheimer's disease and there's been a lot of success stories in animal studies of Alzheimer's disease unfortunately almost none of them translate to humans so it's a wait-and-see maybe they've onto the real thing but I don't I don't know what the context is anyway have you come across data on cell cultures here we go looking at neuronal cell cultures exposed to kittens versus other media cultures to see if it improves or Bible or if we prove longevity of those cells or that studies been done we certainly don't do them I don't have the technology to do it I perhaps someone Tom do you know the answer yeah maybe you could take the mic so your question was if ketones are neuroprotective yes under conditions especially where there's glucose deprivation the administration are adding ketones to a petri dish with cultured neurons will save will have a very nerve protective in that context and regeneration too recently we've shown some studies where there's an enhancement of regeneration which is the neural sprouting and the axons actually growing out of neurons my question is what do you look for in a supplement that you know shows that it's a quality supplement and huh that's a challenge because there are fraudulent products out there and even if the company genuinely believes that that what's in the bottle is what's on the label they may not always be right so what do you look for I mean you can pay I'm sure some independent laboratory to do the analysis but in the end some supplements are not going to contain the active ingredients that you're hoping are there or in the amounts that they claim and and that's that's the state of the art don't put all your energy and money into supplements you can walk the cognitive stimulation improve the diet as well it's not a way it's there's no miracles in this business so there's no single supplement or even a whole pile of supplements that are going to be the solution by themselves in a planned diet that we subscribe to it is considerably inclusive of fruit now does fruit in the sense of production of glucose or sugar or whatever is is fruit within the refined category or is it detrimental by having a diet of fruit well fruit kind of sits on the fence and I mean there's nothing wrong with eating an apple or a banana or as much as you want of them but if the fruit comes in a can or you know it's in some way modified chances are there's additional liquid or fructose around as well so you got to use your best judgment and eat some fruit okay if it's just right but you don't you need to eat fruit for the vitamins for instance or the minerals you ketogenic diet has very little fruit in it and you can get the vitamins and minerals particularly from from vegetables leafy vegetables in focus so if your goal is to get the vitamin content you can do it out the fruit if you like the fruit if you like blueberries I mean go for it thank you okay are there any negative effects of taking a tablespoon of MCT oil every day most people are not sensitive enough to have a negative effect from a tablespoon which was the unit you gave me you don't want to take this much MCT at one shot right you can work up to 50 or 60 grams so that had 60 grams would be about 2 tablespoons starts start slowly find out if your stomach is actually quite sensitive you some people are less sensitive than others so there can be side effects but you can dilute the MCT you can take it twice or three times a day you don't have to take it all at once in fact it's better even if you had no side effects it's better if you spread it out because it allows the ketone levels to last longer in the blood and that's what you're after there's no there's no danger apart from the risk of diarrhea from a large dose some people are constipated and actually look forward to okay do you want to have be ketogenic enough to have ketones in your urine to do this like on the Atkins diet so my experience with the ketogenic that measuring ketosis from the ketogenic diet is from from epilepsy and children and it's notoriously useless it's it's not a very good indicator because you urine volume is going to depend on how much you drink and the concentration of the ketones is going to be the opposite of the volume if the volume is big the concentration is going to go down but you might be screening a fair amount of ketones anyway so it might be simpler in some ways to use the urinary sticks but I don't think they're a good indicator that's my experience from the ketogenic diet for children and I probably applies in in adults as well okay we have you really want to know what's going on with your ketones you can do a finger prick measure it's not that expensive sorry we have one last question here since the human brains about 3 pounds plus or minus a pound and we're told four years now avoid fats and we know that the brain atrophies over a as we age what about omega-3 for the brain will that make a difference over time so the what's called the epidemiology which is the way people eat people that eat fish countries where fish is eaten have a lower incidence of Alzheimer's disease Japan Norway Portugal etc countries like you know which that don't eat much fish have a higher incidence that suggests that fish is protective and I don't challenge that association the problem is if if you don't eat fish and I tell you you should eat fish you're not going to that's the first thing and you're going to try and replace it with fish oil which is a seems like a sensible compromise but all the randomised trials with fish oil capsules in Alzheimer's disease and in mild cognitive impairment have not been successful so does that mean there's something in fish that you can't put in it but it isn't in the capsules I'm not sure but that's the state of the art we're trying to boil down food into capsules and and supplements and stuff and maybe that's not the solution of course if you've never eaten fish and you're not going to then you can eat omega-3 fatty acids from algal sources you can eat vegetarian sources of DHA because alpha-linolenic acid from flaxseed oil is the inert in terms of DHA production you're not gonna make any DHA from alpha linolenic acid I guarantee it so and you everything that's leafy and green has got alpha linolenic acid you're gonna get loads of omega-3 but you're not going to get any DHN there's no alpha linolenic acid in the brain so you need the DHA maybe you can convince yourself to start eating fish but right now it's kind of a there's there's no solution I'm and it might depend on the energy status of the brain anyway if there's not enough fuel getting into the brain maybe the DHA is getting there and it can't do what it needs to do because the neurons are not communicating because not enough energy and the reverse could be true we might be able to optimize a ketogenic supplement with DHA it's not out of the question at all but separately the DHA doesn't seem to be very beneficial it doses that you would expect if it was going to work it should work 800 milligrams a day it hasn't worked that's a lot I would like to thank everyone for being here at this lecture please show your appreciation to dr. Canaan thank you

Channel: TheIHMC

Views: 52,986

Rating: 4.9113679 out of 5

Keywords:

Id: pR8bHXZKZj8

Length: 56min 45sec (3405 seconds)

Published: Thu Mar 08 2018