"Metabolic Therapy in Glioblastoma" - Dr Matthew Phillips

we're delighted to have Dr Matt Phillips here to present this year's brain tumor awareness month webinar Matt is a clinical and research neurologist at waikato hospital in Hamilton his foremost passion is to explore the potential feasibility safety and efficacy of metabolic strategies particularly fasting and ketogenic diets and creating alternate metabolic states that may benefit people with a variety of neurological disorders his team conducted the world's first randomized studies in people with Parkinson's and Alzheimer's and he is currently conducting a clinical trial that combines intensive fasting with a ketogenic diet alongside standard treatments and patients with glioblastoma so Matt welcome and over to you thank you Chris and thank you Vicky I'll just share my screen here so my name is Matthew Phillips I'm a neurologist in Hamilton New Zealand as uh was mentioned I'm originally Canadian so hence the accent the talk is named metabolic therapy in glioblastoma and for the next uh 30 to 40 minutes I'm just going to talk about a program that we've been running here in the waikato region for at least you know close to two years now for people with glioblastoma okay so we're going to start with something called germ Theory now germ Theory theory is a few hundred years old and it was championed by Louis Pasteur who was a French chemist and microbiologist who uh to be honest I uh really looked up to as a kid now germ theory is a disease eccentric Theory it basically States in simplified form that pathogens like bacteria and viruses are the origin of disease so if you want to help someone with a disease process you have to Target and eliminate the pathogens and this really does focus on elimination this Theory um a nice example would be um you know antibiotics to treat people with bacterial infections there was an alternative Theory uh way back when a couple hundred years ago in the 1800s at the time and this was called terrain Theory and not too many people know about terrain Theory I'm sure some of you do though this was uh championed by a man named Antoine Bishop who was not just a scientist but also a medical doctor and he was a contemporary of pastors he was actually a little bit older and they sparred verbally often uh over decades um with respect to their theories now this theory was a more health-centric Theory it recognized that of course pathogens existed but it it viewed most of them as scavengers that really they could only most of them could only instigate disease in a weakened host and so Bishop viewed a fundamental dysfunction in the tissues and cells is the orig as the main problem with these disease processes and this implicated rather than try to eliminate the Scavengers the best treatment strategy here was to restore the tissues and cells or the terrain or the health of the body and so his Focus was on restoration but unfortunately um at the time he didn't really have a very good Target uh you know we were identifying lots of microbes and Pasteur had good targets um for his uh vaccines and so on but Bishop didn't have those so he he ended up saying making recommendations like uh get sunlight and exercise and so on but it was a little bit vague so at the end of the day he lost the debate and uh germ Theory won and germ Theory now provides uh I would say most of what we do in medicine so if we look at standard treatments in glioblastoma current standard of care is the stup protocol this involves surgery so you resect the tumor to an extent that is feasible you have to avoid vital areas of course you give radiation five days a week for six weeks and then you give chemotherapy seven days a week for six weeks and you do this in five day cycles every four weeks so sort of one week on three weeks off kind of thing the student protocol essentially and I'm thinking you know just think broad brush stroke think broadly here it treats cancers as a sort of infection based on it's based on germ Theory it aims to eliminate the cancer cells and and it it has it is really there's nothing about restoring the health of the body in the stiff protocol really other than indirectly through the elimination of cancer cells however we're offering a metabolic Therapy Program and this is a clinical trial so it's highly experimental of course but many people here would know that um there has been some work in fasting and ketogenic diets in in uh in all kinds of cancers and other in other parts of the world so what this metabolic Therapy Program or ntp is is we're adding as an adjunct or or I would I should say in combination or conjunction to the stoop protocol so it's tailored to work with the student protocol and this involves prolonged fast which is serial five-day fast and they're strictly timed to with the standard treatments and I'll show you why and how they're timed and why their time that way and we also involve intermittent fasting which is just uh smaller fasts so eating one or two meals a day on all of the days some days it's one meal some days it's two and we sort of give a program is to 21 and 22. and when people aren't doing the big prolonged fasts we uh they're already in a modified keto diet so every time they're doing the intermittent fasting it's not just intermittent fasting it's also a modified keto diet or ketogenic diet which is very high in fat with adequate protein and very low carbohydrate and so the MTP is based on terrain Theory it aims to weaken the cancer cells but importantly it also aims to protect and restore the normal cells I believe this is a very important thing that we need to do as well so you can see I guess we're trying to combine a pasture with Bichon we're not favoring one over the other it's the combination that I believe uh May yield the greatest success and that's the rationale basic rationale for the trial now I am going to talk a little bit more about um fasting and keto diets for some people the people that don't know much about this prolonged fast um or any fasting really is a voluntary absence from food and drink for specific periods of time usually 2 to 21 days for a prolonged fast anything over two days is really considered prolonged up to three weeks now you can take it a lot longer than three weeks and I've spoken to some people that have done this um the world record I often say this is is uh well over a year it's it's uh 380 something days but that's sort of extreme now on these fast you need water and salt so they can be done as a just a water and salt fast or you can do it by adding in some tea or maybe some coffee just just a bit of black coffee and not too much and some people do fast with a tiny daily meal there's a sort of calorie restricted fast uh that's viable so you can really do fasting many different ways it's not just uh water or you know just water and salt now fasting most importantly it should be seen as a method it's just a way to establish therapeutic ketosis now ketosis is where the body has these energy molecules running all over the place throughout the the blood and the tissues called ketones and ketones come from body fat primarily when you're fasting and ketones have a number of benefits that I'll talk about in a few slides for your normal cells particularly your brain and neurons and your muscle cells fasting can be done uh you know in terms of the how frequently you do it and for how long the prolonged fast can be done anything over two days but uh I think uh going on basically a lot of uh what from what of what I've read and through self-experimentation I got to say as well I believe the five day fast may be optimal for at least glioblastoma I might be wrong there but this is the time course I've chosen for the trial and of course they can be much longer you can do these for weeks or months if you want to but I'm not sure that that is necessarily beneficial now intermittent fasting is shorter uh version fasting so this is something you can do every day you obviously can't do a prolonged fast every day uh infinite forever you know definitely you have to eat at some point but but intermittent fasting can be done every day for sort of 12 to 48 Hours well 12 to 23 hours if it's daily and it this can this is generally this can be water only you don't have to supplement with salt salt is needed in those longer ones to maintain your blood pressure but you don't have to have the salt in these shoulder fasts and you can still throw in some tears and coffee this is also a method it's a less intense method for establishing ketosis but the advantage of this one is you can do it really over the long term on a daily basis and the way intermittent fasting is done is several ways of course you can do time restricted fading so you fast for say 16 hours a day and you eat in an eight hour window or eighteen and six or you know any any variation you want you can do one meal a day that's also known as omad so you have a 23 hour fasting window and maybe one hour to eat all good or you can do two minutes two meals a day I guess I call that t-mad uh and that's a variable window you can sort of uh the way I uh sort of prescribe that is by allowing people to sort of choose the time of the day when they want to eat the tea meals as long as they eat them within an hour immediately is a diet that's uh and I've put this in yellow just because it's so uh often missed it's very high in fat okay it's adequate in protein and very low in carbs so a lot of people uh restaurants in particular when they advertise keto food get the fact that you need to be very low in carbohydrate typically under 50 grams a day but you also have to increase the fat tremendously and that's where a lot of people go wrong with the keto diet I find it's best seen as a method as well so it's it's better seen as a method like fasting rather than as a diet it's a method for establishing ketosis or strategy or you know I call it a strategy in the past for establishing ketosis whereby you generate ketones not from so much from the body but from dietary fat so it's from the food and this can be done multiple ways uh some speed tests have achieved is achieved it can be omnivore carnivore vegetarian it doesn't really matter too much to me I've had patients on all of that all of those regimes as long as you achieve ketosis that's the main thing and it can be many uh different uh ethnic Cuisines it can be variable and dairy I find that some people can tolerate High Dairy and some people can that's okay you can do any any of those I find as long as ketosis is achieved and also it can be high fiber low fiber or no fiber that's okay like some people if they do the carnivore keto diet for example it's really hard to get fiber in there and that's okay whereas if you're doing a vegetarian keto diet it's going to be very it really should be very high in fiber and I've had people do that and that's okay too so it's not about which diet is best they're all methods trying to achieve ketosis okay so now that you understand a bit more about the fasting and keto diet side of things at least from my perspective we'll look at uh more at Medical therapy so how could metabolic therapy such as our metabolic Therapy Program or MTP help people with GBM okay there's a few mechanisms and this is one of the great things about this plan uh this Therapy Program is that it doesn't just sort of make life difficult for our tumor cells from one angle it it hits it from multiple angles so first of all the MTP lowers blood glucose while raising blood ketones now this is really important because glucose is the predominant fuel for GBM cells by far it they can uh probably metabolize uh at least one amino acid glutamine which is the most abundant versatile amino acid in the body and that ultimately comes from protein and maybe uh they can also metabolize some others such as methionine however it's really glucose that the majority of tumor cells in the majority of cancers but particularly GBM that that they rely on that now at the same time it raises blood ketones which they have a difficult time using for energy if they can use it at all and so what we're trying to do here is um is lower the blood glucose and raise the ketones to lower this thing called the glucose Ketone index or gki that is the ratio of glucose in the blood to ketones in the blood so the what you want is uh lower glucose in the blood so less fuel for the cancer higher ketones in the blood so you you swamp them with these energy molecules that they probably can't utilize efficiently if at all I'll talk more about that in a couple slides as well now second way the program works is it it actually augments the resistance of the normal cells to Conventional treatments when when you have a chemo or radiation or any stress coming in normal cells will hunker down and stop dividing and focus on survival whereas cancer cells don't do this so normal cells undergo differential stress resistance or DSR they become more resistant to these uh these stressors such you know particularly the standard treatments at the same time you augment the sensitivity of the cancer cells to those treatments because you're depriving them of their main fuels so you you induce at the same time differential stress sensitivity or DSS so I hope you can see that this creates an environment that's beneficial for normal cells but hostile to cancer cells the third thing and I this is where I sort of take it a little further than most uh people in the in the field I suppose I believe this is a very terrain based uh concept I believe that uh the fast and keto diet um fundamentally restore Health which I Define as the health of one's mitochondria mitochondria are these inner little uh sort of batteries that people call them batteries that are exist in most almost all cells and basically keep the cells going they do a lot more than just make energy though for the cells they do a lot of other things and basically this might be a way if you restoring the health of all the normal cells and this might be a great way to prevent recurrences now I'm speculating there but you know at the end of the day there's no point destroying a tumor if you are also hurting the normal cells around it and producing uh damage and uh you know to their mitochondria and to their genes might induce them to become tumors a couple years later so you have to think of the long game in these cancers and that's what point three is about 0.4 uh and 0.5 these are just a couple extra things if you're interested that the metabolic Therapy Program might induce uh these um we call these epigenetic alterations so epigenetics is just um how the genetic code is read so you have a fixed genetic code but parts of it are sort of turned on parts that are turned off at any one time and the metabolic therapies uh prop there's some evidence that they will create they will allow it to be read in a way that does not favor the cancer State and they may activate the immune system and that's a very enticing concept as well I'm not going to get into that one too much in this talk but it's there now we're going to go through the first three mechanisms in a bit more detail so first of all Lauren glucose and raising the ketones so the MTP metabolic Therapy Program lowers the gki glucose Ketone index and that makes life difficult for cancer cells by depriving them of glucose as I mentioned that's their dominant fuel cell source these cells up regulate their glucose intake by 10 to 100 times it is it is uh it is tremendous and so they're far more susceptible to uh a sort of Choke if you if you lower the glucose they're far more susceptible to that than normal cells at the same time you're swapping all the cells with ketones cancer cells and normal cells and this is a better fuel source for the amount of oxygen a person Breeze ketones make more energy than glucose and there's there's really oh very limited evidence and none of it good if you ask me that uh cancer cells including Global stomach cells can utilize ketones for cell growth now there are some animal studies and a a number of xenograft studies where they transplant cancer cells onto animals and then there's a number there's a little bit of speculation in inferential thinking behind some of these studies that maybe cancer cells can use ketones to grow and survive there is no good evidence in any study to my knowledge that cancer cells can utilize ketones over glutamine and glucose and all these other things to not to survive and proliferate okay now that is a general statement but we have to think in terms of generalities here if we think too much about you know maybe in this case that case this cell can use that's then I think you end up getting confused because nothing's going to to work at all but at the end of the day this is a very important concept that ketones are not a viable fuel source for cancer cells to grow and proliferate now if we look at what this means uh here's the glucose on the left y-axis so the far left bar going down and then we have uh blood ketones on the right now what most people run on day to day because we're you know eating a three meal a day standard Western diet uh which which has a fair bit of carbohydrate in it or even if you're you know don't have that much carbohydrate it's still going to be similar to this the ketones black bar are sort of around six and the sorry the glucose the black bar my bad are around six is around six and the ketones the Red Bar sort of rests in the negligible level around 0.2 or 0.3 shown by the Red Bar there and uh when you do the apply a metabolic therapy um that trend is sort of it's it's it's altered or sometimes reversed now the the y-axis they've shown there are a little different the glucose and ketones is not quite the same so it sort of makes it look like the ketones are way higher than the glucose when you when you get onto a metabolic program but uh it really a good metabolic program when they have the ketones sort of half the glucose level or or maybe even approaching the glucose levels around the same that would be a really good program but that's the sort of zone of managed growth that one wants to achieve where life is difficult for new cells and so the ideal gki in humans is not known but lower is better and at least in animals less than six seems to lead to reduced brain tumor volumes and better survival now lesson six is not that low but it's you know even that that level five or six you start to see effects now at the same time uh metabolic therapies augment conventional treatment so what we're trying to do is induce differential stress resistance and synthesization so we're trying to make the normal cells more resistant to chemotherapy and radiation and make the cancer cells more sensitive so uh in animals this does happen so the metabolic Therapy Program induces normal cells to enter a stress resistant mode making them resilient to radiation chemo and they have fewer adverse effects from those treatments and due to the nutrient deprivation the cancer cells are more sensitive to radiation and chemo so they uh their elimination may be enhanced so like don't look at these diagrams too much there's a lot of stuff in there normal cells uh undergo a lot of metabolic changes shown by all the arrows in there that enhance the resistance to chemo and radiation cancer cells don't do that they they rely on their original metabolic changes that tell them to grow go grow so they don't stop they just keep growing and yet it's hard because they don't have much heal uh so evidence in animals does show that fasting sensitizes cancers including glamus to radiation and chemo and a prolonged survival okay restoring mitochondrial function the third point so uh the the nutrient this is uh there's evidence to back this up as well uh but it is also theoretical it's all theoretical um with some evidence the nutrient deprivation promotes mytohermesis which whereby the mitochondria becomes sort of more resilient in the long run so you stress them a little bit the fasting and keto diet are stresses so that's why they can be a little hard at the start but with time as a person gets used to them the the mitochondria adapt and they become um more robust and function improves it also lessens mitochondria exposure to oxidative stress so fasting and keto diets reduce oxidative stress which might reduce damage to mitochondria and it promotes phytogenesis so fasting does this quite powerfully um mitochondria need to be able to move around and and fuse together and then divide and uh the the sort of uh they by doing this they are able to allow new mitochondria to be sort of born and old junky mitochondria to be recycled and removed and this is an extremely important process that we don't really allow our bodies to enter in too much on our three meals a day uh eating pattern plus snacks so the fasting I think is the real power uh behind this this concept so the basic concept is again you've got to damage mitochondria very simple diagrams and you're trying to make them healthier okay so perhaps by restoring mitochondrial function we can we can knock down some of those occurrences so what is the evidence formidable therapy cancer until now we've we've sort of been discussing animal studies and now I'm just gonna just gonna present human data okay nothing to do with mice there have been seven Interventional studies to my knowledge that have used fasting with standard treatments and advanced cancer in people now collectively this is any cancer not just GBM collectively they show that fasting improves the quality of life improves adverse effects and enhances uh uh that differential stress resistance uh the resilience of the normal cells to these standard treatments there have been quite a few Interventional studies that have explored ketogenic diets Interventional study just means uh a group of people had a intervention applied in this case a keto diet or a fast now the Interventional studies involving keto diets in conjunction with standard shoes collectively show that the diets improve quality of life that's that's fairly firm and you know it was just contrary to what a lot of people might think I guess and same with the fasting that you know you have to oh you can't eat much you know you have to eat a lot of fat actually quality of life fairly robustly improves in both and the keto diets May prolong survival I don't think the uh the evidence is that great uh and the effect is very small if it's there but it's it's probably there and um you know the trouble is we lack randomized really good clinical uh trials and randomized controlled trials in in these in this area okay what about glioblastoma in particular so looking at humans only there's only been two Interventional studies unbelievably that have looked at fasting with standard treatments in global stoma one uh the picture there shows one that we did was published last year now uh the first study only did a single three-day fast and that was basically it so it was very very limited fasting the one we did there involved a series of sort of six day fasts on average over five to six months so it was more rigorous but both the studies were and I include our own were difficult to interpret because um in the first case the fast was were limited in the second case our patients were very uh far past their diagnosis and most of them had sort of completed their standard treatments so months and months passed a diagnosis so we weren't able to overlap and combine the fast with the standard treatments which to me you know is the crucial element that we're talking about here combining pasture with Bichon uh or chair in theory with terrain Theory there have been about 10 or more Interventional studies that have looked at keto diets with standard treatments in GBM and these were difficult to interpret as well because most of them were very short less than 12 weeks and only two of them that I could see measured the gki so if you don't measure that you don't know how powerful the keto diet is right you don't know how much pressure it's exerting so that that's the data in GBM in humans it's quite limited I guess now what we're doing is we're trying to make of course the best uh and most rigorous study out there at least to date so we've designed a comprehensive metabolic Therapy Program for people with GBM that combines fasting and a keto diet which is energy treatments now it involves prolonged fast so we're doing serial five-day fast this is what our patients are doing in this trial the fastest strictly timed with the standard treatments to exert maximal pressure when the chemo and radio uh and radiation are given we this is think of this as a pulse it's like a a brief pulse for a few days of uh powerful treatment against the tumor cells and uh powerful protective influence for people cells and when they're not doing the prolonged fast though are the people and the participants in our trial are always doing intermittent fasting so they're eating one or two meals a day on all the other days and this is sort of oppressed so you're chronically exerting pressure against the tumor cells and chronically trying to restore the health of the neural cells when you're not doing the big fast and of course drinking treatment fasting all they eat is the modified keto diet that's it it's very high in fat adequate protein low in carb and this exerts metabolic pressure too but I think the keto diet is a weaker press it I often like in fasting to Batman and the keto diet to Robin in in our programs I believe fasting is the power in at least this is the way I'm conceiving them and this is the way our metabolic program is designed the keto diet is not the power of the program now our objectives are we have to do this feasibility is it doable because you know these are people with global stoma and you know we're asking them to do a significant lifestyle change is it safe and that's what a lot of uh medical doctors obviously worry about and most importantly I think this is probably the most important one for people with GBM quite frankly is it efficacious does it work does it help improve quality of life survival I'm going to give you uh a look at the protocol here in the last 10 minutes the metabolic Therapy Program basically represents this is an important concept it is the most intensive metabolic therapy that has ever been applied to a group of people with any advanced cancer not just glioblastoma and it's applied for a minimum of nine months okay during all the chemo radiation and adjuvant chemotherapy that works out to be about nine months so what happens here is a person with GBM is of course diagnosed with a biopsy and then they they have resection of the tumor now not all our participants some people are unlucky and the tumor is so deep or in such a vital structure it cannot be surgically resected and we have uh 25 of our actually close to 30 about the people in the program are that inoperable okay so we are taking um some of the most difficult and I should say we're only taking idh negative uh the sort of wild-tech glioblastomas no astrocytomas and um so so we're really trying to keep it to the hardest um of the hard here that we're taking the most uh the glioblastomas with the sort of worst prognosis now we apply or I should say the oncologists apply after this surgery chemo radiation so as I mentioned the chemotherapy and radiation combined for six weeks uh some people get less but but the patients in our trial get six and during that time we start participants on a five-day fast three to four days before they start the chemo radiation now the reason for this is to after three days your glucose is pretty low of fasting your glucose is low your ketones are pretty high and so we get People maximally Protected and maximally hostile environment for the tumor before the chemo radiation starts so we want people we hit hard right from the start of this program super hard okay so we're making life real difficult for the tumor cells and the neural cells are protected then we hit with chemo radiation so I hope you can appreciate that this is a real super intense approach not just uh with the key the standard sheets with with the metabolic program now after they do that first five day fast two and a half weeks later they do another this is a second hit and the idea is you sort of I'll use a colloquial language I guess that you've got the tumor on the ropes potentially and now you hit it again with a second five day fast two and a half weeks is not a lot of recovery time but we're finding that it's enough after the generation there's a four week break where there's no chemo radiation and people just do their one or two meal a day ketogenic diet then there's the adjuvant chemotherapy which is six months so for the chemotherapy that's given as I said before uh five day cycles so daily for five days and then nothing for just over three weeks and then another five day cycle so first would be Cycle One the cycle two cycle three and so on up to six every time there's a cycle we before the chemo is given three to four days before the chemo is given guess what we do yes we give we start another five day fast so we're trying to get the body uh the glucose low the ketones high and and sort of the the tumor maximally stressed metabolically before the chemo hits again and of course the normal cells are maximally protected as well and we do that six times over six months so there's a lot of pressure and afterwards technically the standard treatments for most people are done at this point but and and this is where I give everyone who's got who gets out here uh we have uh well four uh five arguably because there's a pilot patient who who have completed all their standard treatments and asked them well what do you want to do you know this is what I'd recommend we probably should you know if you want to keep exerting pressure particularly if you're doing well and all the people out this far are doing well if you want to have done well if you want to keep exerting uh pressure you might want to keep up the intermittent fasting and the keto diet but uh perhaps just forego the five day fast and so everyone basically is still doing that and they're still measuring their ketones and I'm still reviewing them every two months that's the program in a nutshell and it's it's registered there at that URL on the internet if you want to look at it again or you can just look at this talk again I guess now in terms of feasibility uh I'll just give you a little bit of preliminary data I I uh can't give too much because the trial is of course we're only halfway through but basically everyone is measuring their blood glucose and ketones daily during the standard treatments and afterwards indefinitely as I mentioned so this is what it's looking like for the first nine to ten months so for during uh chemo radiation and hydrogen chemotherapy the blue bars are the glucose the red bars are the ketones and I've made them all on the same access so it doesn't look a bit exaggerated like that other chart I showed you did so what you can see here is that uh Baseline the mean blood glucose before they start the metabolic program everyone's got a blood glucose of just over six and the ketones are negligible to build about 0.3 and I got to say I gotta say two or three of the participants started a sort of a a a weaker version of a keto diet before they they entered because they were they were enthusiastic so that's okay but probably the ketones would have been even lower if it wasn't for for that but anyways 0.3 and um you can see in chemo radiation there uh the left two bars red and blue are weeks one to three the right two are weeks four to six you can see that the glucose uh drops down it doesn't look like a huge drop but that's that's a decent drop down into the high force and the ketones go up quite a bit so 2.5 or so so the ketones are about half the level of the glucose level and for the rest of the nine to ten months the participants are maintaining a very good um glucose uh level and a very good Ketone level so you can see they're sustaining this this is almost up to a year and to my knowledge this kind of um this kind of uh metabolic pressure has not has not really been shown in a group of people case reports one people one person reports it has but not in groups of people in in the literature now what does this mean if we look at the gki that glucose Ketone index which is really the important variable at Baseline the gki is close to 20. so that means um you know the glucose of six and the ketones are 0.3 6 divided by 0.3 or so you've got something close to 20. so it's a terribly high gki and that is basically if this metabolic theory is correct that is a cancer-loving state okay there's glucose everywhere and there's very little ketones now if we look at chemo radiation once people start the metabolic program The gki Falls to two now two remember less than six in animals is efficacious against tumors two is pretty good pretty darn good and uh you know I really get a lot of um a lot of the credits of the participants here they're just very adhere um disciplined and adherent and dedicated to the program and over the nine to ten months absolutely up to a year almost here it's stained within the two to three range so they're maintaining a strong gki during the five day fast I should also mention it's it even is more powerful than this because during those five day fast the mean gki I've calculated it it's it's about one so during this you know all these bars are shown here but within here we have these pulses where the gki is really choked off reduced down to one and hopefully that's helping uh the these people do good things for their bodies and and not so good things for the tumors what I want to say here is collectively in this trial the participants are sustaining therapeutic gki so far this is the we only have 11 patients that have enrolled in the trial I should mention and we're aiming for about 25 but so you know we have half the numbers it's preliminary data and it could change but so far it's looking very very promising in terms of taking we are measuring adverse effects using this well-validated uh sort of uh adverse effect form that uh all the oncologists use of the ctcae it's an acronym common uh terminology in cancer at versus vets so we're assessing any and all adverse effects and the oncologists are actually doing this as well so it's combined between the the oncologists and myself regardless of where they come from but the standard treatments the metabolic program or if the patient people are unsure and then uh there's a second questionnaire that I'm administering if a more focused checklist that okay says okay if there was a side effect that the CTCA identified is it from the standard treatments the metabolic program neither unsure trying to figure out which what's the source of the adverse effect to the best of our ability oncologists people in trials with drugs often get excited when you don't have an adverse effect hot you know if it's a one two or a three grade one two or three that scene is pretty good we've had nothing over grade two so all the adverse attributed to the metabolic therapy um there have been three or four attributed to the standard treatments um low platelet counts and white cell counts mainly nothing too sinister but that have been grade three or grade four nothing to do the metabolic program and this is over a long period of time now our pilot patient is at two and a half years now okay I haven't mentioned that but our pilot patients at two and a half years the first person in the trial is at about uh 20 months nothing's been overgrade too lastly I'm going to talk about body weight changes because a lot of people do worry about this so if we look at the body weight changes in these 11 patients over nine to ten months almost a year on this highly intensive metabolic program you can see that people are losing about 10 of their body weight and it's not dropping below that now uh unintentional weight loss is a problem in people with cancer because it indicates malnutrition and ongoing muscle loss but intentional weight loss if you look at the literature uh and it and with in the setting of a properly applied metabolic program a metabolic Therapy Program with fasting and keto diets done properly you get mainly almost exclusively fat loss as the source of the weight loss and the muscles are largely spared okay there is a little bit of muscle loss but with all the fat loss we find people's function often improves because they got less weight uh proportionally more muscle than they had because they've lost a lot of weight but almost all of it's fat and even though I've lost a tiny bit of muscle there's so much less body weight there they can actually do more so and also if you look at the literature intentional weight loss such as gastric uh Banning procedures and so on where they force weight loss through surgical methods those people have a lowered risk of developing many types of cancer so intentional I'm trying to get across here is unintentional weight loss is undeniably bad but all the weight loss in this trial is intentional and we're also looking at body mass index this is the last slide on the prelim uh second last or BMI now if we look at the BMI over 90s people that started the program were overweight uh 25 to 30 BMI is overweight range 30 plus is obese Ranch now after nine to ten months the average person most people are normal weight and they're actually still high normal they're bmi's around 24 which is good normal is 20 to 25 but you know even though you could argue losing a little a little bit more would still be you know not a problem they've still been in motivation now given the nature of the metabolic program which is largely a fasting protocol this is absolutely not surprising it would be expected and logically You could argue and I would I would favor this the normalized BMI could be perceived as ideal right we're trying to improve the health of these people part of a healthy body involves being a normal weight so intentional weight loss getting people in normal weight range I would argue is a good thing okay now efficacy this is of course what is most important to people with GBM now we are looking at changes in function like performance status we're looking at changes in exercise activity we are looking at changes in quality life and we are looking at of course perhaps the most important thing overall survival effect and I I am sorry I'm not going to give the data at this talk it is far too early and it would I think it would be a bit irresponsible for me to to give the data I don't want to get people's hopes up and then have things change because I respect Global stomach for what it is it can look like it's very tame and quiescent and suddenly it can you know sort of go uh go get really aggressive so I hope that if I give a similar talk in 6 or 12 months then I can start showing some data but probably uh you know with scientific um research one should try not to speculate too uh too much ahead of the data and I've I've already given some data on on feasibility and safety that I think is reasonably sound and I don't think it's going to change but it could so I apologize for not giving you uh evidence on whether you know it's affecting these four efficacy things however uh I guess I would say we wouldn't still be doing the trial if we weren't seen um some uh positive um it changes I'll just leave it at that in conclusion standard treatments in cancer are based on germ Theory Journal Theory aims to eliminate the cancer cells whereas metabolic therapies are based on terrain Theory this is a hugely important concept that we do not teach in medical school we focus almost exclusively on germ Theory related treatments metabolic therapy based on the terrain Theory concept aims to weaken cancer cells and protect and restore the normal cells which I believe is just as important as taking out the tumor cells these approaches are not exclusive okay so the the application of standard treatments in conjunction with metabolic therapy is my belief that this may yield the best outcomes in people with cancer now I may be wrong here guys however I do think we we can improve on the current student protocol and the standard care and and maybe it doesn't involve a totally different treatment but complementing that protocol with something like this that can sort of mitigate the damage of the student protocol to the normal cells and even enhance its effects against cancer we are applying a highly intensive metabolic Therapy Program in conjunction with the standard treatments for people with EDM and although luminary data is indicating visibility and safety we've got to be cautious about that even and I I cannot comment uh with any degree of strong uh rigor uh with respect to efficacy we need more time we need more patience uh fortunately another hospital Wellington hospital um I'm hoping looks like it may be joining us in the next couple of months we'll see how that goes but that's it for my talk and I'm really happy to answer any questions oh Matt thank you for that that was um absolutely fascinating and a great talk um yeah I think I think Vicki's vigorously monitoring the chat box because I've seen some activity there so there's bound to be plenty of questions have you got any from the chat box Vicky maybe um while you're doing that maybe I'll ask a couple of the questions that we received earlier um I I think you may have covered this bit but um in terms of when to start the program what's the optimum start Point does do they need to start it at the chemo radiation phase or um do you think people can still do the diet after they've finished treatment and it could still be of use yeah it's um the trouble is um without Chris's is the standard treatments have gone on for two or three months I guess if this theory if I'm looking at it correctly then we've already done another a fair bit of damage to the tumor but also to the normal cells and applied metabolic therapy later obviously you've got more damage that you're trying to mitigate and uh so it's ideal I think to start it as I said before the same treatments the the first fast starting three to four days before the standard treatments to get people in that mode where the it's hostile cancer and protective for normal cells and then you just maintain that mode in a pulse press fashion for the next uh few months and I hope you know but potentially years so I think earlier is better but again you know this is uh this is uh theoretical and a little bit speculatory in my part but that's what we're doing yeah yeah no I can say that I can understand that um Becky is there anything from that so there's the question about how can we use the MTP after we've survived the standard protocol phase this is someone who's um talking about two years post operative and standard protocol with clear scans I've been using keto diet three I haven't not been fasting okay well first of all congratulations it's very that's great um that you're using the keto diet so you know when we get to this point when people have done this nine to ten months of standard treatments and they and then we sit down and we go well what next because often the colleges um just sort of follow them with serial scans but don't have any more treatments to offer I guess my recommendation is that ideally if you want to keep the body healthy keep the brain terrain healthy and sort of prevent those recurrences because that's the big fear if you've done a great job on that primary tumor you don't want a recurrence then it's best to maintain your metabolic program now if you're having great success with the keto diet alone but by all means just keep doing that I guess my idea is that from from the research I've looked at the keto diet alone in most people is not sufficient to um prevent recurrences it's it's good to slow growth and maybe stall it for a bit but I think but I don't think it it prevents occurrences as many people and that's why I like to throw in the fasting as well and we're in an evidence-free Zone there with the the sort of long-term one or two meal a day fasting with keto diet that's you know combining these treatments often people look at fasting or a keto diet we're use we're looking at both so we're not just combining standard treatments with a metabolic program we're also using a mixed metabolic program to try and hit the tumors and restore Health multiple angles hope that answers the question there's another question on whether you think this program would improve healthy brain cell production and cell regeneration in post ischemic stroke survivors that's a good question um yeah it might so if you look at back to animal data because this has not been looked at much at all but when investigators induce Strokes in mice like they they cause a stroke and purpose mice that were in ketosis for a few days beforehand like fasted for example they have strokes or infarcts a stroke is a dead area brain tissue from lack of blood supply lack of oxygen their their final stroke is about half the size or less than the stroke that was applied to the animal that was not in ketosis so that's direct evidence that uh being in ketosis makes the stroke much smaller now in terms of having a stroke and then applying a Fastener keto diet strategy after the fact nobody knows if you can enhance uh regeneration of neural tissue so on there is neural regeneration in human adult brains throughout life but it's it's only in a couple areas it's and it's very small so what happens in Strokes is more that normal neurons Around The Strokes take over for the the the dead cells rather than uh regeneration um filling in the dead cells thank you uh I don't know if you've had any of any information on this but someone's asking about is there any data on people who don't want to do the chemo radiation but just want to do the metabolic program uh awesome question ah boy uh is there data on that not not too much to my knowledge I mean there are case reports we published one for example uh four years ago but it was not in global stomach it was in a metastatic cancer a very bad one a thymoma and this young lady did no chemo no radiation no surgery she couldn't have any of that stuff because she was deemed to palliative and offered palliative chemo which she refused she did a similar protocol to the medical Therapy Program and this is you know created some of the my inspiration for doing it in people with gvm she did a seven day fast every one to two months and a keto diet in between and she's you know I saw her last week with her husband and her little girl six years now uh after being given one year to live and she's full quality of life looking really good so but that's an exception and that's a different tumor so I I'm not sure that that this would be um I I've I've had I actually I've had uh one guy who did fasting keto uh only uh without chemo radiation and GBM and you know he he I don't think he had any enhanced survival this was a few years ago um he didn't do the keto diet very well though he he tended to focus a lot on the desserts which had a lot of sweeteners and so uh I learned from that and decided that our metabolic Therapy Program can't have very much sweetener in it because it has bad effects too so there's not much evidence at all and I I guess my thoughts would be maybe a you know even stronger metabolic program that focuses hard on glutamine part of methionine and all these other things uh could be helpful in people who don't get the chemo radiation but for some of these big tumors and inoperable tumors I I think there's a lot of aggressive cells that you need to you need to hit with the standard treatments at the same time yeah Nate can I just ask a follow-on from that you mentioned glutamine and methionine are they [Music] um of those levels enhanced by the ketogenic diet well nobody knows the answer to that really um one thought is that you know we have two or three people who love you know uh typically younger men prefer the carnivore keto option because it's easy and you completely choke all glucose right because you're just eating um steak and chicken and uh things like that and you're putting it in some coconut oil well or you know animal fats or or something like that um it's possible that they do um I guess by layering by focusing more on the fasting aspect of the metabug therapy so so again our program focuses more on the fasting maybe that can have beneficial effects against uh you know excessive amounts of amino acids that could potentially be a fuel for tumor cells but it's really important to to always think big picture I think with these things I think if I can be um the point something out that in the literature a lot of scientists really focus on one molecule or one amino acid or or one thing and I'm trying to look at things I really try to look things in the bigger picture and I think glucose is by far the dominant Fuel and then this by far number two is glutamine by far so if you know if you're focusing on the donor Fuel and maybe hurting glutamine a bit you're probably doing a pretty good job against GBM metabolism would be ideal to choke all the other things sure um however you know I it's it's hard to get glutamine blockers there are drugs that block glutamine um and uh you know I don't know how to even get them to be honest and I'm in contact with Professor Thomas Seyfried semi-regularly who is is uh you know kind of like the leading guy in this and uh anyways yeah so you're trying to focus on the forest and not worry too much about the trees I think with these programs otherwise you'll just go crazy and you'll it'll be hard to design anything and I've got a question so people who've got high cholesterol and have been on statins can they how do they go about going on a ketogenic diet so in a program we've uh got a couple people with heart attacks in the past statins it's not a problem okay okay and I realize that is a controversial statement however there's no evidence zero evidence that keto diets or fasting of course uh are in no way caused it for heart attacks and strokes I'm a neurologist I see ischemic Strokes all the time so what is the problem is the standard Western diet is highly correlated which has remember there's so much confusion in the literature so the standard Western diet is 30 fat 50 carb on average 20 protein that is high fat and high carb now when you make carbs so by energy intake our diet has sort of 75 80 fat maybe 15 protein and five percent carb so when you uh you know when you augment one of the macros but choke another one um I think that is a very healthy thing because the mitochondria only have to metabolize one thing mainly and conversely not in cancer but in other settings high carb as long as it's good carb with fiber and low fat can be good too for that reason if People's mitochondria only have to focus on metabolizing carb and they don't have to worry about a huge influx of fat that can be okay too the problem is when you try to mitochondria are damaged I think very much so by constant meals throughout the day where it's high fat and high carb we call this a metabolic gridlock they're trying to metabolize both Pathways at the same time they can't renew themselves it's it's it's terrible state for mitochondria and I think that is bad in for cancer and that it's bad for heart disease and so on so I I think you know I will say that um none of I've had people on keto diets and fasting protocols for a number of years now never had any kind of cardiac problem a heart attack anything like that occur on a therapy but it is controversial yeah uh one's asking about patients with diabetes as well why is that long gone um does the pathway work well for them oh well we've had a couple people with pre-diabetes in the trial um if their uh diabetes pre-diabetes gets better um quite quickly I've had people in our Alzheimer's and Parkinson's days of type 1 and type 2 diabetes type 2 diabetes quite frankly goes into remission quite quickly and this was just on a keto diet alone never mind the fasting yeah type 1 diabetes and Pros too you just got to be a little more careful with them because as they go along they're going to have to use less insulin because they don't need it as much so look um it's there's actually a scores of studies in the literature in people randomized trials good studies that show type 2 diabetes is put into remission or at least severely improved on fasting and ketogenic diet protocols that is uh for some reason still unknown by a lot of people and doctors included but it is is absolutely true and I don't even look at that anymore because it's it's fairly Rock Solid to me I've I've seen enough type 2 diabetes going to remission I'm not even trying to do that I'm trying to improve the Alzheimer's or something else right and so I keep an eye on the diabetes but it that it goes down is absolutely no surprise to me and uh but but it is a surprise to some colleagues I remember a neurologist colleague of minor a few months ago didn't know this and he was amazed and I was just I was amazed that he was amazed but there you go I think a lot of people are interested in joining the um the clinical trial no so well I would love to have good to hear good to hear that Wellington might be um might be doing something similar then yes the oncologist Wellington were great I gave a talk a few months ago and they approached me and they're very interested so we've done the ethics uh most of the ethical requirements and I I hope that we get them on site soon we can start enrolling people in that region Matt there's a question about uh dexamethasone are any of your patients in the trial on dexamethasone and um yeah I allowed onto the trial and how do they how do they go in terms of their glucose Ketone ratios yeah excellent question so dexamethasone is a steroid that um is often used in glioblastoma to reduce swelling around the tumor because the swelling itself can make people have uh neurological problems we go on weak legs seizures and so on so dexamethasone is often given to produce this one it's quite effective at that the trouble with dexamethasone is metabolically it's good long short term good short term because it makes people's quality you know function better bad long term what dexamethasone does is it raises glucose and drops ketones unfortunately and so uh you you don't want to have high dexamethasone doses uh for very long periods of time in a metabolic program now that being said you know I allow up to four milligrams daily of Dex and that's something for people entering the trial as long as it's on a reducing dose and the oncologists are all well aware of this and um the dexamethasone uh after that if if people have um often people are getting a treatment effect so sometimes on a scan a global schema looks a little bigger but it's it's actually a lot of it's swollen and dead and we call that a treatment effect it's quite common we see that in standard treatments alone too and a treatment effect where the tumor gets a little bigger before it gets smaller can produce problems including swelling so the oncologists might want to prescribe higher doses of decks that's fine uh I find that it does affect the glucose levels it does increase them it does drop the ketones but not that much and they don't need to be on steroids that long so I was deathly worried of that a couple years ago but I'm not as worried about anymore it's not ideal but it's not the end of the world if people have to go on eight milligrams of decks for a little while okay great any other questions there Vicky otherwise we um we're after 8 30 and we were scheduled to go to 8 30. so um I think there may be a few more questions I'll save the chat box and perhaps pose those to um Matt afterwards and maybe we can work out how to get get some answers to them but just the the number of questions and messages in the chat box are reflective of the of the interest in uh the topic and um Matt I think it was an excellent presentation thank you for taking the time out to present to us and also to answer all the questions that you have well thank you very much for the opportunity and uh I'll keep you posted on how we go

Channel: Brain Tumour Support

Views: 3,764

Keywords: glioblastoma, ketogenic diet, brain tumour, fasting, metabolic therapy, GBM

Id: QNS0aYn1QJQ

Length: 60min 26sec (3626 seconds)

Published: Thu May 25 2023