Click here for the full video: Robert Lustig, MD - Food, Metabolism, and Psychiatric Disease

Video Statistics and Information

Video
Captions Word Cloud
Reddit Comments
Captions
Good afternoon everyone. As part of our Emery  Pharma seminar uh speaker series I'm honored   to present to you an accomplished speaker whose  work really has had a significant mark on our   comprehension of nutrition and well-being and sort  of the intricate connections that bind them. Today   it's my privilege to introduce Dr Robert Lustig  to our Emery Pharma speaker series. Many of us are   very familiar with some of Dr. Lustig's work,  particularly on The Perils of excessive sugar   consumption and its implications for health. His  viral lecture, sugar the bitter truth has actually   gained millions of views I've seen that myself  and sparked worldwide discourse on the detrimental   impacts of sugar particularly on human health  as an accomplished author Dr Lustig has also   penned several influential books including fat  chance, beating the odds against sugar processed   food obesity and disease uh it's actually a book  that my wife's company actually has for all of   their Physicians but really delves into again the  scientific inquiries behind or intricacies excuse   me behind the Obesity epidemic, but beyond these  scholarly and you know advocacy Pursuits Dr Lustig   holds the position of a Emeritus Professor for  the division of Endocrinology, the department of   pediatrics at UCSF University of California San  Francisco um and today he's going to delve into   some of the connections that intertwine food  metabolism and psychiatric disease. So please   join me in welcoming a a warm welcome, Emery  Pharma welcome for Dr Lustig. Thank you Ryan,   thank you Ron, thank you Ana, thank you all, you  know again I'm kind of like part of the extended   family so I've talked to you about metabolism and  systemic health Health in the past and today we're   going to talk about metabolism and brain health  mental health and what the connection and what the   role of food is in metabolic health of the brain  and I will make the argument during the course of   the hour that in fact mental health is metabolic  health of the brain okay that the two are actually   indistinguishable and the same processes that are  going on perect Al to cause disease are going on   centrally to cause disease and the treatments  guess what are the same real food we're gonna   we're going to go there and you'll see why okay  so again I always have to start with disclosures   okay so I did write these books for the general  public and metabolical has a lot of what I'm   talking about today uh I'm chief medical officer  for these four companies and I'm a paid advisor   to the these other and uh I'm specifically I'm an  adviser to the UC Davis Innovation Institute for   food and health who's looking at all of these very  specifically okay and I'm also the chief science   officer of a nonprofit here in the Bay Area called  eat re uh whose mission is to get real food into   kada2 nationally okay all right starts here starts  with 1920 okay when physicians at John's Hopkins   University realized that patients who were in  diabetic keto acidosis who also had concominant   seizure disorders stopped seizing when they were  in keto acidosis okay and so people said well why   is that and so they started experimenting with  the ketogenic diet and they found lo and behold   getting people to be ketogenic that is is lowering  their insulin and inducing fat mobilization and   oxidation via ketones because ketones are the  breakdown products of fat led to a cessation in   seizure frequency and seizure severity in these  patients and so then people started experimenting   with ketogenic diets in other things and then of  course we had the Atkins diet and then of course   you know moving on and now of course everybody  is just flagrantly keto all over the world for   all sorts of reasons including our colleague  here Mark who has lost 30 pounds and had his   alt go from 80 down to 24 right do I get it right  yeah okay so this is a good thing and the question   is you know do you have to be that extreme and  is does it work for everybody and why does it   work in the first place so that's that's where  we're going so it's possible that the ketogenic   diet could prevent seizures through metabolic  effects that are direct at the brain or it   could be through gut microbiota effects because it  changes the microbiome the ketogenic diet changes   the microbiome because it provides different  nutrients than were there before so you expect   different bacteria to glom onto that differently  and so there's the possibility of changing your   amino acid profile therefore changing what might  be excitatory at the level of the CNS all of   these things could potentially lead to changes in  seizure susceptibility well then people said well   could the ketogenic diet help with other types  of brain problems aside from seizures now my   colleague and now good friend Christopher pmer  at Harvard Medical School was the first person   to recognize this possibility he was presented  with a guy who had severe manic depression who   had tried everything that was refractory to  all medical therapy he also happened to be   300 lb and the guy wanted both help for his bi  bipolar and also help for his weight and Palmer   didn't know what to tell him but he said you  I've heard about this ketogenic diet you know   maybe that'll help your weight and turn turned out  not only did it help his weight but his bipolar resolved and since then he's gone on to treat  numerous patients and have developed K series   and now is doing clinical trials with you know  uh randomized control trials to determine whether   or not the ketogenic diet will actually fix  manic depression schizophrenia and multiple   other CNS brain SL mental health problems and  in fact now there's actually a literature on   the ketogenic diet in Psychiatry now this talk is  not about the ketogenic diet this talk is about   food okay in general and how it might impact  but it gives us a a a window into this issue   and this problem and the reason is because the  ketones don't need insulin to work they don't   need insulin to enter cells and they don't need  insulin to stimulate energy uptake they just   get in there's no transporter for ketones they  just get in so if you've got lots of ketones in   your blood they're going to get to your brain  okay and don't need any help there's no key un   loock here they just go and so that might be a  reason why it might be better but it also might   be because the insulin went down and that might  be better we don't know yet so the question that   Christopher asked is could food or even fasting  be a psychopharmacologic therapy and that's where   we're going today now many investigators many  clinicians many scientists many pundits have   postulated a relationship between metabolic and  mental health and that they might actually be the   same and here are a bunch of different books we've  talked about some of them today at lunchtime so   David pearlmutter wrote brain maker uh Fel Jacka  down in Australia wrote brain changer a lot of   brains here okay uh my colleague Bill Wilson in L  Massachusetts wrote brain drain and then em Meyer   who's at UCLA and does microbiome uh work uh  wrote The Mind gut connection and you know and   Christopher Palmer's new book Brain energy which  uh is actually perhaps the best of the bunch and   this hasn't escaped um shall we say the cognic  you know in academic medicine because this is   from Lancet okay and here's this is a very  important quote the emerging and compelling   evidence for nutrition as a crucial factor in  the high prevalence and incidence of mental   disorders suggests that diet is as important as  Psychiatry as it is to Cardiology endocrinology   and gastron neurology I couldn't agree more  and it's nice that somebody at Lancet figured   that out because i' be honest with you they  haven't figured out much of anything else so food what can you do to food to either make  it good or bad okay Real Food Works but clearly   we're not eating real food 73% of the items in  the grocery store are not real food they are   ultr processed food and is that Ultra processed  food actually impacting our brains in a negative   fashion that's the question so what are they  doing to food well you can add something you   can add vitamins and Omega-3s you can subtract  something like artificial colors or allergens   these are all out of you know ultr processed  food to make the food better you could change   the macronutrient composition or the timing so  you could go vegan you could do Tim restricted   eating you know or intermittent fasting you  could alter the microbiome which I think is a   great way to do this and the easiest way to do  that is not with a probiotic but rather with a   Prebiotic because a Prebiotic will allow the right  bacteria to grow a probiotic won't that's why you   have to keep taking a probiotic because after all  if a probiotic worked you'd only have to take it   once it's a live culture why doesn't it just set  up shop the first time the reason is because the   internal mil of the intestine is so inhospitable  that's why those bacteria are not there in the   first place that's how they got killed off that's  why you need the probiotic except that you haven't   fixed the mil so like why would you expect it to  work because it won't take so fix that first and   that's called fiber okay and then of course all  the above and you can do that with a ketogenic   diet now why would these work why could these food  manipulations have beneficial effects in terms of   psychopharmacology CNS is central nervous system  it could alter CNS energy metabolism that is   making the mitochondria work better to make more  ATP it could alter CNS neurotransmission we're   going to talk about the glutamate Gaba cycle in a  minute it could alter trophic factors in the CNS   like for instance leptin and bdnf brain derived  neurotrophic factor which cause neuronal outgrowth   and in some cases neurogenesis it could alter CNS  exposures like toxins and infections one of the   big ones is strep and I think you all know this  because all you have to do is go back to 1791 when   syum demonstrated that a strep infection caused  severe choreoathetosis called cims Korea due to   rheumatic fever okay like why would a bacteria  cause a change in your central nervous system well   you know we've known that for a long time and of  course all the above and the ketogenic diet does   all those okay so the ketogenic diet again it's  our window into the problem it's not the only   issue but it's a window okay could potentially  have lots of different effects it could change   energy consumption because the mitochondria don't  need insulin and it gets in so it's you know if if   you have a you know Ketone level in your blood  it will make it into the brain and potentially   you can have more efficient ATP production okay  or it could change neurotransmitters over here   so it could change the Gaba to glutamate balance  you know a lot of people forget that glutamate   is the precursor to Gaba okay and so there's a  glutamate to Gaba cycle and that is under the   control of different enzymes that are manipulable  and glutamate is excitatory and Gaba is inhibitory   and so if you have a problem converting one to  the other guess what you might go freaking crazy   and in indeed people do okay gurg transmission  changing glutamate transport Ang which could   lead to angiolytic effects Etc okay everybody  got it in addition maybe more cholesterol and   cholesterol can be converted to pregnanolone which  can then be converted to Alo pregnanolone an Alo   pregnanolone binds to the progestin receptor and  can cause reduction in CNS output so it's a smile   sedative okay and maybe even improve immune  function too all of these plus there are fats   that matter in this story so there are Omega-3s  like EPA and DHA ioso pentenoic acids and DOA   hexenoic acid the EPA DH a and you get these from  where you get these from wild fish not farmed fish   okay and these are necessary for normal neuronal  membranes and normal neural transmission and I   will show you in a minute that these are very  important in terms of uh emotional well-being   and mental health on the other side you have omega  sixes and Omega sixes all come from this guy over   here linolic acid which is in seed oils and this  is pro-inflammatory because it is the precursor   to arachadonic acid and arachadonic acid is  the precursor to prostaglandins thromboxanes   and lucrin all pro-inflammatory so we know that  inflammation of the brain leads to mental health   disorders and so keeping that inflammation  down is necessary so you need a Omega 6 to   omega3 ratio that basically allows for normal  neural connectivity and transmission and doesn't   allow for inflammation well that Omega 6 to  Omega-3 ratio optimally should be about 1:   one maybe even up to 3:1 4:1 our current Omega  6 to Omega-3 ratio is 20:1 and the question   is does that have detrimental effects well we  know that poor psychiatric health is linked to   persistently low Omega-3s in fact significant  depression and schizophrenia too all with low   Omega-3s now is that an epif phenomenon is that  a primary phenomenon is it correlation is it   causation obviously you can't tell from this kind  of study the only way to know that is by doing the   clinical trials and seeing whether you can do  that I'm going to show you some so this leaves   us to the question of what is is going on in the  brain what makes a difference is it the ketones   is it the type of fat is it the elimination  of carbohydrate or all the above and is very   specifically because it's my interest what is  Sugar's role in this and is the reason that any   of this works just because you're getting rid of  sugar which is possible I'll show you why so we   know that if you do any of these things you will  improve insulin sensitivity well that will lower   the amount of insulin at the level of the neuron  which is good because insulin makes the neuron   do other things other than what you want it to do  okay actually basically drives energy metabolism   in the wrong direction because you're in storage  mode not burning mode and your brain wants to be   in burning mode not storage mode and it turns out  beta hydroxy butyrate which is the primary Ketone   it's not the only one AC acetoacetate is another  one but beta hydroxy butter is the primary one   from fat metabolism turns out it's a signaling  molecule it stimulates the cell to make cerin   in particular S 2 and two which is a primary  driver of mitochondrial biogenesis so you're   making more mitochondria which is good okay so  is it the Improvement in instant sensitivity or   is it the reduction in Sugar consumption itself  we don't know because no one's ever tested just   sugar reduction against carbohydrate reduction  to find that out out so these are still open   questions and every time I go to a talk or a  symposium about metabolic Psychiatry this is   the question I ask and no one can answer it yet  okay and I'm going to be the biggest gadfly in   the world asking which of these or both is is the  important issue in why this matters don't know yet   is it the carb reduction or the sugar reduction  that matters and through what mechanism I care I   think you all care too okay so when we talk about  sugar reduction what are we talking about well   we're talking about two molecules right dietary  sugar I.E sucrose is two molecules one glucose one   fructose bound together with an glycidic linkage  linking the two high fructose corn syrup is one   glucose one fructose not bound together okay now  the enzyme in your intestine SU C Cleaves this Oly   AIC linkage in a nanc you absorb both molecules  separately and they do their own thing glucose is   the energy of Life fructose is consumable poison  it's that simple well if you consume high fructose   corn syrup you're getting the same thing so this  whole concept of sucrose versus high fructose corn   syrup is you know just a tempest in a teapot it  is just garbage okay they're both equally bad   okay but of course the sugar industry thinks will  tell you it's the high fructose corn syrup and the   high fructose corn syrup industry will tell you  it's the sugar and you know because they're all   competing for market share all right now what is  going on in the brain well you got to measure so   if you inject glucose or fructose or both into  somebody's vein and then do magnetic resonance   spectroscopy of their brain here's what the  glucose reference looks like here's what the   fructose reference looks like here's what the  combination looks like it's basically those   two put together and this is a human being okay  who's just eating and you see they're both there   okay they're both there and the reason is because  the human brain turns glucose into fructose this   is work from Rick Johnson at the University of  Colorado and you can actually measure this as well   so this is pregnant women pregnant women here's  the CSF to plasma ratio for glucose that makes   sense because the CSF glucose level is always  half of what the blood level is that's normal   here's for fructose okay why is there fructose in  the brain and why is there more because the brain   converts glucose to fructose now why that's  a complicated story and Rick would tell that   story much better but there's actually adaptive  advantages to that and of course Sorbitol is the   way you get from glucose to fructose this is the  polyol pathway so basically Aldos reductase makes   sorbitol and then it goes to um uh fructose and  fructose has its own potential effects all right   so there's fructose in your brain whether  you like it or not whether you ate it or   not all right it's just a question of how much  and what's it doing well what's it doing it's   changing your mitochondrial metabolism is what  it's doing all right so impaired mitochondrial   function and psychiatric disorders so this is not  like my you know you know imagination it's not   my you know craziness you know other people have  been looking at this and so here's mitochondrial   function right here in the center and you can  see there are a whole lot of things affecting   that okay there's bcl2 which is a anag gene that  causes cell division mitochondrial DNA mutations   glucocorticoid receptor translocation changes  in calcium influx okay that all Impact uh oh   and most importantly reactive oxygen species  we're going to come back to that in a minute   okay all impacting on mitochondrial function  in fact we have a paper that we've got uh uh   sent out uh for review right now on the role of  active oxygen species in the toxic effects of food   okay and why it drives obesity not why it drives  psychiatric disease but it's the same thing okay   and when your mitochondria don't work right you're  going to have problems with synaptic plasticity   neurite outgrowth ATP production apotosis calcium  homostasis okay are which are all going to have   behavioral effects now remember the ketones get  get into the brain without insulin right so here's   the liver making ketones beta hydroxy butyrate  right here entering the brain right here okay and   basically going to both the asite and the neuron  the beta hydroxy berate ends up going from the   asite feeding the neuron and you end up into the  kreb cycle so that you can burn it but you don't   need insulin to do that whereas every other cell  you know if it's glucose you do need insulin to   do that right so that's one of the reasons why  the ketogenic diet might work is because you   don't need insulin so ketones can substitute as a  CNS energy source even when the mitochondria are   dysfunctional even when they're not working right  they will work better on ketones than they will on   glucose because getting from glucose to AAL COA is  its own process which can be affected negatively   whereas ketones bypass that and go straight to the  CB cycle okay and you'll get less oxidative stress   less reactive oxygen species when you're burning  ketones over when you're burning glucose and it's   been shown that the ketogenic diet can improve  cognitive parameters in Alzheimer's disease   maybe every patient with Alzheimer's should be  on a ketogenic diet well Dale breson who wrote   the end of Alzheimer's thinks that that's true  okay now hasn't been tested in a formal fashion   needs to be okay but in his case series which he  has just published that's one of the things that   allowed for survival of Alzheimer's was going on  a ketogenic diet now why is this a problem I mean   what's going on to alter the mitochondria well  that's in this slide here and I think I've shown   this slide at you at Emery Pharma before I love  this slide it's one of my favorite slides okay   here's glucose here's fructose they are not the  same okay the food industry will tell you calories   a calories sugars a sugar garbage total complete  trash okay they say that on purpose because that's   how they assuage their culpability for putting  all the fructose in the food in the first place   they are not the same and this slide shows that  they're not the same glucose actually stimulates   mitochondrial function so you'll notice beta  oxidation up arrow in green hooray that's good   glucose increases mitochondrial function how  does it do it activates two enzymes right here   activates am kinas adenosine monophosphate kinas  this is the fuel gauge on the liver cell when your   cell uses up ATP it makes am right because the  phosphate bonds get broken and that's where the   uh energy is is in those phosphate bonds that's  what the electron transfer support chain in your   mitochondria do is they basically release the uh  uh energy and you turn n into nadh and then go   back and forth Etc you know that's that the whole  oxida phosphorilation that powers cells everybody   familiar with the concept right okay well amp kyes  okay if you have more amp it fits into the active   site and what that does is that tells the cell not  enough energy we're energy depleted because I'm in   I've got instead of ATP and so we need to make  more mitochondria so it increases mitochondrial   biogenesis which is good for burning more energy  in addition it increases this enzyme here called   HH hydroxy Asal COA dehydrogenase which is also  involved in increasing the rate at which two   carbon fragments get converted into energy thus  beta oxidation go going up so glucose for lack   of a better word is good fructose on the other  hand is another story fructose does the opposite   fructose inhibits three enzymes that are necessary  for normal mitochondrial function it inhibits   ayase it inhibits this one down here called aad L  ailoa dehydrogenase long chain which is necessary   to cut up those two carbon fragments and it also  through uric acid inhibits this over here cpt1a   carnitine pido transferase 1A this is the enzyme  that regenerates carnitine and carnitine is the   shuttle mechanism by which the fatty acids get  from the outside into the mitochondria for burning   in the first place the sum total of which is that  beta oxidation goes down glucose beta oxidation   goes up fructose beta oxidation goes down they  are not the same clearly Ron Khan CEO of Joslin   who was the senior author on this paper famously  said about this paper the most important takeaway   of this study is that high fructose in the diet  is bad it's not bad because it's more calories   but because it has effects on liver metabolism to  make it worse at burning fat as a result adding   fructose to the diet makes the liver store more  fat and this is bad for the liver and bad for   whole body metabolism and that's just the molecule  itself never mind what it did to the insulin right well that's one problem there's another  problem okay and it's on this slide and I've   shown this slide here as well you're all familiar  with this concept now here are five pictures of   food they all share one thing in common what  is it they're all delicious brown brown yes   but they're all brown they are delicious and the  reason they're delicious is because they're brown   okay that's the caramelization or the uh Browning  or the myard reaction the myard reaction this is   of course what causes hemoglobin A1c okay so the  way to think about this is you can roast your   meat at 375 degrees for an hour or you can roast  your meat at 98.6 de for 75 years the answer is   the same your Browning and if you don't believe  me here's newborn rib cartilage nice and white   and here's 88-year-old rib cartilage is nice and  brown okay you are Browning as we speak and if you   had orange juice this morning you are Browning  seven times faster and that Browning reaction   is the Aging reaction it is what causes wrinkles  it is what causes cataracts it might even be what   causes Alzheimer's disease might how does it work  well as you know glucose has a ring form and a   linear form this is the linear form when glucose  is in the linear form it has an alahh at one end   at position one and that alahi will bind to an  Epsilon amino group of Lysine at position one   of the hemoglobin molecule forming a shift base  which will spontaneously decomposed to this Cove   valent linkage which then has to be cleared by  the spleen and that takes three months and that's   why measuring your hemoglobin A1c basically  tells you about your glucose burden over the   previous 3 months that that's why diabetics can  use it to monitor their efficacy okay everybody   with me so far okay well not only does it occur  in glucose and every by the way every time that   reaction occurs it releases a little reactive  oxygen species a little oxidative stress which   has to be quenched by an antioxidant or it will do  damage it will cause lipid peroxidation or protein   denaturation ultimately causing cell dysfunction  ultimately cell death ultimately organ death and   ultimately human death okay just does it over  a long period of time like one cigarette won't   kill you okay 100 cigarettes in one day won't kill  you but you know what 10 cigarettes over 20 years   will most definitely kill you okay takes a while  but nonetheless it's still toxic even if it's not   an acute toxin it's a chronic toxin same idea here  okay this is a buildup slowly of damage and turns   out that glucose will do it and you can't stop  it it will happen if you're alive it's going on   but you can slow it down and fructose does it  too and it does it seven times faster and you   can actually measure this in not just the body but  in the food because when you heat Ultra processed   food the fructose in the food binds to the Epsilon  amino group groups of Lysine in the food to create   Advanced glycation end products in the food itself  and there's a receptor for the advanced glycation   end products called rage receptor for advanced  glycation end products and when you stimulate   that Rage with an advanced glycation end product  you generate reactive oxygen species all by itself   so eating food that has been uh that has add  sugar in it and bound is also problematic okay   and it correlates with cardiovascular disease in  patients with obesity now why does this happen and   why is fructose particularly egregious for having  this happen that's here and this is our paper from   uh our kids study okay this is the important term  right here delate now you've h a lactate lactate   is what your muscles make right when you exercise  right lactic acid that's L lactate this is delate   the isomer right the epimer okay Del lactate only  has one source and it's not exercise I will show   you so there are a lot of different things  that affect that amp kinas right it is the   master regulator of all of these Pathways and  it promotes all these good things and it also   inhibits all of these bad things so turning on  your kyes is a good thing that's why metformin   is now being utilized for type two diabetics and  possibly even as a longevity promoting agent near   barsel is you know running this metformin trial  out of Albert Einstein to see whether or not   metformin can promote longevity by increasing amp  kyes by increasing mitochondrial function okay so   there's a a a a a theme here if you will okay so  MP kindness is pretty important and I agree it is   so let's look at amp kyes a little closer three  subunits Alpha Beta gamma that gamma subunit is   the B where the active site is that's where the  fits in to the pocket okay and that pocket over   here okay has three arginines three arginines  three places where something could bind and form   that myard reaction Well turns out a compound  that is made from an intermediary metabolite of   fructose called methylglyoxal methylglyoxal it  is the breakdown product of dihydroxy acetone   phosphate okay can fit in that active site and  it is an alahh and what happens when an alahh   and an amino group find each other right so here's  the myard reaction if if if glucose is uh if the   rate of the glucose at the myard reaction is one  fructose is at seven methy glaxal is at 250 so   meth oxil is a bad guy okay because it is binding  to proteins whether you like it or not okay and it   fits in the active site so it fits in that AR you  know finds one of those arginines in that active   site so the methylglyoxal gets made from dihydroxy  aone phosphate from fructose fits inside there and   then you turn off your kyes irreversibly you have  basically killed your amp kyes so your MP kindness   goes down what does that mean for mitochondrial  biogenesis means it's in the sewer means you have   decreased your mitochondrial function and if you  decrease your mitochondrial function what does   that mean for your cell means your cell starving  and is that going to have any behavioral effects   if it's in your brain you bet it will everybody  got the idea okay now methylglyoxal has a way   of being Det toxified to deact remember I told you  deact was important this is the source of deact is   methylglyoxal detoxification by an enzyme called  glyoxalase one glyoxalase one is in all your cells   but different people have different levels of  the glyoxalase one it's genetically determined   so some people will be able to get rid of their  MGO and some people won't so we measured deact in   our obese patients and guess what it's 52% higher  okay and in our kids study where we got rid of the   fructose and substituted glucose deact went down  by 38% in 10 days so the fructose gets converted   to MGO the MGO basically takes the am kyes out and  so now you've got denova lipogenesis glucogenesis   cholesterol synthesis all bad and all the good  things are all inhibited because amp kyes has gone   down the tubes not good all because of fructose  and methylglyoxal okay so that's how mitochondria   might be affected so far so good we got three more  to go loads of fun now we'll do neurotransmitters   remember I told you glutamate to Gaba the link  is the intermediate glutamine glutamate goes   to glutamine glutamine goes to Gaba but it's a  little more complicated than that because there   are different cells and there are different  stoppage points on the way my colleague and   good friend Monica Duce at University of Michigan  studies all this in fruit flies and showed that   if you take fruit flies from a controlled diet and  put them on a sucrose diet it changes their entire   brain structure entire brain structure just  because you added sugar to their diet okay my   colleague Bill Wilson who wrote that book Brain uh  uh drain okay he is a clinician he looks he does   pattern recognition and he's taken care of like  6,000 obese patients and he stuck them all in DEA   scanners so he could actually measure their body  composition and he also gave them questioning and   he found 22 specific symptoms that correlated with  metabolic dysfunction and here they are read them   they're all behavioral they're all behavioral  okay they're all really common maybe you have   them okay and he calls this because when he puts  people on low carb diets they all get better so he   calls this carbohydrate Associated reversible  brain or carb syndrome and he actually runs a   Blog called carb syndrome. org which you can  you know access for free okay so I've looked   at this question and in my book hacking of the  American mind suggested this model so here are   the five things in the last 50 years that have  changed in our society technology process food   sugar sleep deprivation drugs each of these has  been shown to increase dopamine increase reward   but dopamine downregulates its own receptor  so the more dopamine the less fewer receptors   therefore you need you get need more and more to  get less and less this is called tolerance okay   because ligans downregulate their own receptor  now that makes you feel lousy because you can't   get the reward signal like you should then throw  some stress on because the cortisol inactivates   the pre frontal cortex and the two of those  together lead to addiction conversely these   five also are all associated with the development  of metabolic syndrome a metabolic syndrome causes   a change in the liver so that tryptophane instead  of being converted to serotonin gets converted to   cyanine which is a different metabolic pathway  so you're basically depleting serotonin because   you're basically fishing it out of the blood and  turning it into this non-helpful curine which   actually promotes inflammation so your serotonin  goes down that makes you dymic makes you feel you   know lower emotional well-being then throw some  stress on which of course cortisol decreases the   serotonin 1 a receptor now you have few lians  less receptors now you got clinical depression   so addiction and depression are two sides of the  same coin driven by the same toxic environmental   stimuli it's just a question of Who's Who as to  which one you get maybe get both now why does   this happen remember I talked about glutamate to  glutamine right well here's glutamate so glutamate   becomes glutamine glutamine then and goes from  the asite to the neuron gets converted to glut   back to glutamate and then goes to Gaba all right  so it's a complex Dynamic it's a complex cycle but   as you can see glutamate ends up as Gaba this is a  better picture of what's going on anatomically so   here's the glutamatergic neuron making glutamate  it enters the asite where this enzyme here called   glutamine synthase GS will turn that glutamate  into glutamine right here then that glutamine will   exit enter the gabaergic neuron and the glutamine  will get converted back to glutamate by glutamate   dehydr uh glutamine dehyd glutamate dehydrogenate  sorry and then GL glutamic acid decarboxylase will   turn it into Gaba so the glutamate ends up here  via glutamine and then that glutamate becomes   Gaba everybody see how that works so this enzyme  here matters turns out that enzyme is inhibitable   by fructose so if you incubate rack cortical  synaptosomes with glucose or with fructose   you get different answers you get completely  different metabolites so look at the glutamate   to Gaba ratio when you incubate with glucose  basically 3: one okay do it with fructose 50 to1 lots of glutamate very little Gap  but because you've inhibited glutamine synthes and this is true in immune cells and  therefore likely true in CNS cells because immune   cells and CNS cells are very similar and you can  see here we're giving glucose or we're giving   glucose and fructose sucrose glucose or sucrose  okay the difference is sucrose has fructose and   glucose doesn't right and we're looking at cyto  and we're looking at so tnf Alpha we're looking   at il1 beta we're looking at IL 6 okay and  you can see that in each case the fructose   made those cyto much higher right and that can  be inhibited by a protein synthesis inhibitor   Romy in other words this is a protein issue and  fructose is inhibiting that okay and when you   put glucose into immune cells you get lactate  and lactate is okay here this is L lactate when   you put fructose in it basically inhibits the  ability uh uh to metabolize it because it won't   let the glutamine get turned into Gaba okay and  you end up with increased oxygen radicals so you   increase your oxidative stress in immune cells  same thing happens in neurons okay number three   trophic factors insulin leptin and bdnf so Ultra  processed food increased psychological distress   as an indicator of depression this came out one  week ago from a Melbourne study big Melbourne   study okay now this is correlation not causation  this is also correlation ultr processed food   increased risk for depression why well insulin  resistance is a driver of depression and it's   a driver of depression through inhibition of brain  derived neurotrophic Factor here and also glycemic   disregulation here all leading to depression now  what do we know about these trophic factors leptin   is a trophic Factor leptin causes new neurons  to form and causes neuron outgrowth leptin is a   trophic Factor insulin inhibits leptin insulin  blocks leptin signaling we know that leptin   causes neurons to branch and connect we know that  leptin regulates neural and gal protein levels we   know that leptin corrects cognitive defects who  have in patients who have leptin deficiency so   leptin is important it's a trophic factor and  you can actually see under the microscope the   uh increase in neurite outgrowth and increase  in synaptogenesis in response to leptin we know   that Sugar causes insulin resistance we know that  insulin resistance causes leptin resistance the   hyperinsulinemia blocks the leptin signaling this  is part my work actually and we see it in humans   as well again correlation not causation it's hard  to do causation in humans because that means you   would have to take somebody's brain out okay and  they don't let you do that not too often anyway   okay but this is a a correlation study out of the  white hole study in the UK sugar intake from sweet   food and beverages common mental disorders and  depression perspective findings now we showed in   our kids study that um uh fructose makes lots of  triglyceride makes lots of vldl when we take the   fructose out of the diet and substitute glucose  nine days of isocaloric fructose restriction   liver fat went down 22% turning sugar into  fat went down 46% vldl triglyceride went down   49% visceral fat went down 7% all good and most  importantly the pancreas started making insulin   properly again in other words we reverse the  patient's metabolic syndrome with no change   in calories no change in weight just by getting  rid of the toxin the fructose possibly through   methylglyoxal possibly all on its own this has  been independently confirmed by another study done   out of UC San Diego and Emory okay showing that  the control group no effect on liver fat and the   treatment group where you took the sugar out Mega  reduction okay now bdnf turns out to be The Driver   of improved mental functioning due to exercise  due to exercise okay so bdnf increases well sorry   exercise increases bdnf increases hipocampal  volume increases memory function aging reduces   bdnf lack of Serotonin reduces bdnf I already  showed you lack of Serotonin is part of metabolic   syndrome okay and that's reducing hippocampal  volume which is also leading to cognitive decline   how about addiction so could one ingredient lead  to Addiction in food and the answer is well yeah I   mean we already know about alcohol okay but turns  out sugar and alcohol metabolize the same way and   Sugar's addictive you know National Geographic  said why we can't resist it in fact that's right   and I can prove it I can't prove it anybody know  what this is anybody ever been in a normal newborn   Nursery at a hospital this is called sweeties  sweedies this is a 24% super concentrated sucrose   solution that you dip the p pacifier in and stick  in the normal newborn boy's mouth before the circumcision the Jews have wine everyone else has  sweeties because they do the same thing okay so I   can prove it right so what's going on in the brain  well what makes a milkshake rewarding is it the   fat or is it the sugar turns out it's not the fat  it's the sugar how do we know because Eric sty at   Oregon Health Sciences University constructed this  great Contraption all out of plastic okay with two   bottles one with fat one with sugar and when you  suck okay you get different amounts depending on a   regulator that he controls as to how much fat and  how much sugar makes your milkshake okay so you   can have a high sugar lowfat milkshake or a high  fat low sugar milkshake okay and he stuck people   in an MRI scanner while they were sucking on the  milk shake to determine what was happening to   the reward center and it turned out that the fat  did not stimulate the reward center the fat only   stimulated the smata sensory cortex mouth feel  only sugar stimulated the nucle cumbent the reward   center and increasing the fat did not increase the  reward so it's the sugar that actually drives the   reward in a milkshake this has been repeated in  a different way from a a group in Switzerland uh   vulneren okay who showed no satiety or fullness  with fructose compared to glucose and no insulin   rise with fructose compared to glucose but when  they looked at the fmri the glucose basically   stimulated the anterior FAA and the basil ganglia  whereas the fructose stimulated the whole lyic system how about dementia so do sugar caused  dementia well D breson would tell you yeah   okay so we know obesity is associated with  dementia that's old news we know obesity   has altered neural projections consistent with  dementia we know that Sugar generates insulin   resistance and hyperinsulinemia old news we  know that insulin resistance and high insulin   levels are associated with dementia we know that  the Western diet correlates with dementia and we   know that both fat and sugar can cause obesity in  rats but only sugar causes cognitive decline fat   does not that's probably because of the effect  on the mitochondria okay so here's bdnf right   and synaptic plasticity okay here's diet and  exercise affecting mitochondrial function okay   the mitochondria make reactive oxygen species  which can affect cognition unless something   takes those reactive oxygen species and quenches  them and gets rid of them you reduce the numbers   okay well it turns out insulin is a bad guy  in the story the higher the insulin the less   well that happens and it turns out that insulin  and fructose induced hyperinsulinemia changes   membrane characteristics and Alters what is known  as membrane fluidity which has to do with how well   does a membrane bounce back when perturbed either  from biochemical changes or pressure changes a way   to think about this I think I talked about this at  the first talk the 8 you have a balloon okay just   a plain old you know birthday balloon you blow it  up you put a knot in it you try to put your finger   through it okay bounces right back now if you try  to take a pin it will explode okay take the same   balloon new new balloon same same concept blow  it up same level put it in the you know corner   of your bedroom for three weeks it will slowly  but surely deflate right now undo the knot blow   it up again to that same level now try to poke  a hole with your finger now it'll now it'll blow   it wouldn't blow before but it will now because  the membrane has changed because of the pressure   that's membrane fluidity everybody got the idea  well that happens in neurons okay and fructose   and hyperinsulinemia change that membrane fluidity  but there's a way to fix that that's with Omega-3s   because it contributes to neuronal structure  remember EPA and DHA and it turns out that   Sugar consumption correlates with Alzheimer's  preclinical Alzheimer's in population studies   how about cognition this is work from Antonio  conit at uh NYU showing that insulin resistance   as measured by the quick ey score is positively  correlated with changes in hippocampal volume   so more insulin lower hippocampus and also more  CSF so you've lost tissue you've lost tissue and   you've got more CSF not good and that correlates  with changes in executive function and cognitive   flexibility here's your few vales okay this is  an adolescence adolescence so you want to know   why all the kids are doing bad in school because  the hyperemia and what's the hyperemia from the   processed food okay how about Behavior I love this  I mean we're in San Francisco everybody knows what   the twinkie defense is right yes who does not  know what the twinkie defense is you all know   oh you don't you don't know the twinkie defense  oh my God where have you been didn't you see the   movie milk milk Harvey Milk Harvey Milk all right  so as you know Harvey Milk was the first gay uh   legislator right and as a Board of Supervisors of  San Francisco you know that part and you know that   he and mayor George mcone were killed by another  supervisor who was a former police officer named   Dan White and at his trial the uh lawyer the  attorney for Dan White tried to defend White's   actions by saying he was insane because he ate  a junk food diet a lot of Twinkies and so this   became known as the twinkie defense now as it  turns out the jury didn't buy it white went away   for 25 years got released one later one week later  he killed himself that's the story of Dan White   okay point is there might be something to this  twinkie defense because it turns out adolescents   who drink more than five cans of soft drinks  per week are more likely to carry a weapon more   violent with their peers family members and dates  even after controlling for all the things that   might affect their behavior obviously correlation  not causation but you know makes you wonder soft   drink consumption is associated with behavior  problems in 5-year-olds increased impulsivity   lack of being able to sit and concentrate and  finally number four the microbiome now this   gets complicated the gut microbiome may be very  specifically related to CNS development and we   know this because of germ-free mice so they don't  have a microbiome and they have cognitive defects   so the microbiome might actually be supplying  things to your brain now might be through the   blood things that get across or might even be up  the afron vagus nerve anterograde transport like   of serotonin cuz 90% of the serotonin in your body  is in your gut there's very little serotonin in   your brain okay it might be getting there through  the afron Vegas through anr transport so if you   change the microbiome you might be changing  your neurotransmitter levels okay we know the   ketogenic diet Alters the microbiome also in some  very specific ways okay having to do with with   Improvement in cognitive function we also know  that the intestine has three barriers there's   the mucin layer is the physical barrier there's  the biochemical barrier the tight Junction and   then finally there's the immunologic barrier the  th17 cells which make il17 which basically keeps   all the pathogens out if you destroy the mucin  layer which could be from emulsifiers we talked   about it lunchtime okay it might be more likely  that bad guys will get through if you destroy the   tight junctions like for instance celiac disease  or sugar as you'll see in a minute more likely   bad guys will get through and if you destroy the  immunologic barrier same thing more bad guys get   through so this looked at the microbiome in  associated with fructose consumption and I'll   just read you the one sentence because this is an  awfully complicated concept that associated with   fructose seem to hold more potential to induce  host metabolic disturbances compared to glucose   mainly by promoting bile acid deconjugation and  torine release and compromising intestinal barrier   Integrity fructose Alters intestinal barrier  integrity and how come because fructose nitrates   those tight Junction proteins and makes them  unreliable so they're supposed to basically hold   like this in response to Sugar they go like this  and it might be because fructose changes the ATP   content of intestinal ocytes and makes them ATP  depleted because of that mitochondrial function we   talked about okay got it and so that could lead to  bacteria and lipopolysaccharide translocation into   the liver and now you've got hepatic inflammation  and insulin resistance and high glucose levels can   activate t 17 cells in inflammation also okay and  there is a pathway between the gut microbiome and   autoimmunity that runs through this IL 17 as well  because of an increase in inflammatory cyto kindes   due to micro microbiota disbiosis possibly  due to short chain fatty acid reduction in   association with sugar consumption I've already  shown you this go keep going okay and this might   be relevant to clinical medicine because dietary  intake of sugar is associated with increased   disease activity in lupus in a patient you know a  patient with an inflammatory process sugar makes   the inflammatory process worse okay association  between consumption free sugars and number of complications and here might be the reason  why we know about Sim's Korea right we know   about a disease called pandas anybody heard of  pandas p n D- Progressive autoimmune neuropathic   disease associated with streptococus disease  related to strepto cacus synm Korea is like   the early famous one but now a lot of kids  have thing this thing called pandas and as   a pediatrician Pediatric and chronologist  I saw this in the hospital okay it's a big   problem well might be because the strep is  growing okay and making bad stuff it makes   toxins okay it makes toxins on your tooth to  eat a hole in your tooth right the strap strep   mutans here okay and strep the caucus in your  intestine so here we're growing group a strep   on different media 2% glucose oh sorry here's  glucose notice no effect here's sucrose huge   effect here's fructose huge effect sucrose  plus glucose same effect so in each case   the group a strep is preferring the fructose  as a substrate for metabolism so increasing   the sugar in the diet might be increasing group a  strep colonization leading to psychiatric disease uh I'm going to pass this for time so let me just  finish what I've told you food has effects on the   brain okay I mean I don't have to like convince  you of that you already know that but like what   okay it's not just growth but also Behavior  food can act centrally or peripherally can   act via the gut of the liver via afret mechanisms  or could act directly via the blood brain barrier   to alter neuronal function food can act as  an initiating or an aggravating factor for   many psychiatric diseases it can affect brain  metabolism through changes in mitochondrial   function through glutamate neurotoxicity through  insulin resistance and its effect on leptin and   bdnf or through microbiome dysfunction leaky  gut and autoimmunity now the ketogenic diet   seems to affect many of these I'm not saying  everyone needs that but maybe certain people   do okay we don't know if it's due to the sugar  restriction or the carbohydrate restriction or   the insulin reduction or the ketones themselves  because of the cin effect we don't know yet but   might be able to treat some of these pathologies  and this is what Christopher Palmer at Harvard is   doing okay anecdotal data and case series support  the association but we need the randomized control   trials they are now ongoing so we have a ways  to go not there yet but I hope what this has   done this talk has given you some idea about  how important this concept of metabolic or   nutritional Psychiatry is and the fact that our  current disaster debacle of mental health is not   just because of the stress of our politics or even  the stress of our cell phones but actually might   be because of the stress of our diet too so with  that I'll close and of course answer any questions   and you know thank you for [Applause] attending  so uh Rob as we discussed obviously sucrose uh   basically it's a you know molecule that contains  both glucose and fructose right and fructose is   a single molecule right SU R is a combination  of two tiny little molecule right so and what   you're showing is effectively glucose in many  aspects seems to be safer compared to fructose   sure compared to compar toose why why aren't we  using glucose more oh cuz it's not very sweet   cuz it Doesn't generate that reward system okay  okay you don't see people going around chugging   kro syrup do you okay that's glucose not very  interesting okay might be good in a cookie but   you know I mean that's only after you add the  fructose first okay glucose has a sweetness   index of 74 sucrose has a sweetness index of  100 and fructose alone has a sweetness index of 173 okay so it might be just due to the  sweetness but more importantly it's the   reward signal sorry so diet sweeteners have  a very high sweetness index they you know   in the hundreds but most diet sweeteners do  not stimulate the reward signal and so let   me ask you a question have you ever had  a no sugar diet sweetener only chocolate bar are they good no no no they're sweet  are they good no T do you ever want another   one no why not doesn't because you didn't  stimulate the reward center just because   you got the sweetness didn't mean you got the  reward okay they're not the same so it's less   about the sweet and has more to do with the  reward signaling and fructose specifically   drives that reward signal binds to receptors in  on the neuron itself so how do you satisfy that crave without causing metabolic disease ah  so invite me back and I will give you a talk   that I'm going to give two weeks from now in  uh North Carolina called the true purpose of   nutrition and the true purpose of nutrition is  metabolic health and so the question is if the   true purpose of nutrition is metabolic health and  if Ultra processed food only causes metabolic D   function is ultra processed food food well could  you make Ultra processed food healthy yes or no yes yes if you know what the principles that  you had to abide by are now the current you know   ultr processed food industry they don't care  they don't know but any better I don't they   do they actually do I know they do because they've  told me they do okay but you know it's about money   it's about money they're not going to do anything  that's going to alter their gravy train okay not   until they're told to have to not until there's  regulation okay and they told me so there you   know that's that's their stick okay it's about the  money they're not in business to feed the world   they're in business to make money and anything  that interferes with that is not is not welcome   period could you make ultr processed food healthy  well yes by adhering to three principles and this   is what uh we did with a uh this company in the  Middle East called Kuwaiti Danish Dairy company   kdd okay and um we wrote this up and uh it was  published in frontiers of nutrition in March   okay three precepts if you adhere to those three  precepts you can make Ultra processed food healthy   those three precepts are and they're in the paper  protect the liver feed the gut support the brain   those three why those three protect the liver how  ah how so get rid of the toxins okay so fructose   is a toxin cadmium is a toxin Branch chain amino  acids are toxins to the liver okay feed the gut   well what does the gut want to eat fiber and  support the brain okay well how do you support   the brain short chain fatty acids which can come  from that fiber okay another way is um Omega-3s   okay and few other you know uh things you know  getting rid of all the other stuff and basically   preventing the inflammation so you have to stop  the leaky gut well how do you stop the leaky   gut well I just showed you the three the three  barriers you got to keep those intact could Ultra   processed food keep those those three intact and  the answer is yes if you know what you're doing   right now that's not happening so actually Ultra  processed food could be made healthy and that's   what we did for kdd and we're hoping that we can  get other food companies on you know this track   to basically alter their uh products and their  fair to ultimately become metabolically healthy   yeah I have a two questions um so one one of the  slides you were talking about how the membrane   the separation is not tight IT wi oh the the leaky  gut okay leaky gut is that is that similarly the   reason why fat might get stored in the liver  or is that it could be it could be especially   for medium chain triglycerides probably not for  um uh uh kyom microns because kyom microns get   made from regular uh triglyceride and you know  they're big fluffy things they probably don't   make you know they're made on the other side  of the membrane anyway and they circulate via   the lymphatics and go straight to the liver and  get cleared through the LDL receptor okay and so   it's a slightly different um pathway for them but  medium train Trias rides could certainly do that   because they go through the portal system so they  yes leaky gut could affect those and uh there was   another slide where you were talking about uh how  sorry you were talking about how fructose inhibits   uh your ability to retain leptin or or consume  leptin no no fructose induces insulin resistance   and hyperinsulinemia and Insulin blocks leptin  signaling at the level of the brain so how how can   we increase the leptin uh sensitivity sensitivity  sure yes well get rid of the thing that's causing   the leptin resistance okay now most people say  obesity is the cause of leptin resistance that's   not true obesity is a marker of leptin resistance  but it is not the cause the cause is what's   happening at the leptin receptor itself What's  blocking leptin from signaling and obesity is not   it triglycerides are triglycerides block leptin  signaling but hyperinsulinemia insulin blocks   lepin signaling so and of course hyperglyceridemia  is associated with hyperinsulinemia so that makes   it doubly worse thank you uh Rob uh one more thing  you talked about ketogenic diet and its potential   benefit for uh potential TNS for certain patients  disorders and so forth what are the downside of   extreme ketogenic diet uh ketogenic diet is  already extreme I know what is it what is the   potential Downs well so if you have familial hyper  cholesterolemia you can't be on a ketogenic diet   because you can't process the LDL because your  LDL is going to go up on a ketogenic diet and you   need the LDL receptor to be able to internalize  and if you can't internalize now your ldls are   super high and you're going to get a heart attack  and die so that's one in 500 people right right   off the bat in addition there's a disorder called  type five hyper lipopro Mia which is a different   disorder it's not f H it's it's type five and it  is hyper hyperchylomicronemia okay you can't clear   the kyom microns and you can't be on a ketogenic  diet you have to be on a lowfat diet for both of   those okay in general a ketogenic diet will  work for most people it will the problem the   problem is most people who go on a ketogenic diet  don't monitor themselves what should they monitor   well they have to monitor their ketones so it  can either be urine ketones which is messy it   can be blood ketones which is doable or it can  be breath ketones I actually am an adviser to   a company that makes a breath Ketone monitor  called Journeys metabolic okay uh used to be   called readout Health they rebranded and they make  a breath Ketone monitor so you can actually it's   looks like a kazoo and you can basically determine  whether you're in ketogenesis or not based on your   breath and if you fall out of ketogenesis then  you have to get yourself back in so it's a method   for self-reinforcement point is if you are left  to your own devices and you're just going on a   ketogenic diet based on a book you read like the  Atkins Revolution okay you can start out ketogenic   and within two months you will be back on your  regular diet and if you're trying to be on a   ketogenic diet and you're not monitoring yourself  the likelihood is that carbs have you know invaded   your diet and you didn't even know it they've  increased your insulin which have suppressed   your ketones so you're not on a ketogenic diet  now you're on a high fat medium carbohydrate diet   which is the actual absolute worst diet you can  be on that's the best way to get a heart attack   so if you're going to do a ketogenic diet you  got to go all the way how about monitoring your   cardiovascular LD you know LDL well LDL will go up  on a ketogenic diet dietary fatting increas is LDL   but it's the large buoyant LDL we talked about  at the first uh meeting okay not the small Den   the small Den are the problem the large buoyant  they're just cardiovascularly neutral so you have   to know which LDL you're uh you're uh increasing  and if it's if it's large buoyant well so what do   would your normal blood test that you do at Kaiser  or HMO tell you that no it won't tell you that but   you can sort of glean it because you look at the  LDL but you also look at the triglyceride so if   you have a high LDL and a low triglyceride then  those are large buoyant that's okay if you have   a high LDL and a high triglyceride then those are  small dense and then that's not okay so in each   case it's the triglyceride that's the big problem  not the LDL LDL has a hazard risk ratio for heart   disease of 1.3 so if you have a high LDL you  have a 30% increased risk for heart attack Fair   triglyceride has a hazardous ratio of 1.8 so  if you have a high triglyceride irrespective   of your LDL you have an 80% increase risk for  heart attack 30% risk 80% risk which is worse   the triglyceride is a bigger problem than the LDL  ever was the reason why everybody looks at the LDL   why everybody thinks that's the guru of all of  this is complete and utter [ __ ] okay because   because because number one triglycerides don't  mean anything if you're not fasting and a lot of   people when they do their fasting lipids are not  fasting okay because a lot of people forget and   then they're at the doctor's and then oh well  you know get it anyway okay so triglycerides   can be all over the place if you're not fasting  that's for sure and number two we didn't have a   drug for it we had a drug for LDL satins okay it  was a long time before we had a drug for hyper   triglyceridemia we do it's fibrates but fibrates  are expensive and fibrates have side effects and   so you know nobody wants to do that but fish  oil will work if it's wild fish wild so that's   that's the uh the key any other questions  anybody any any other questions let's give another [Music]
Info
Channel: Emery Pharma
Views: 207,282
Rating: undefined out of 5
Keywords:
Id: VM8TY_FCm-Y
Channel Id: undefined
Length: 78min 11sec (4691 seconds)
Published: Sun Oct 15 2023
Related Videos
Note
Please note that this website is currently a work in progress! Lots of interesting data and statistics to come.