Rhonda Patrick on Diet-Gene Interactions, Epigenetics, the Vitamin D-Serotonin Link and DNA Damage

so as Bonnie mentioned my name is Rhonda Patrick and I am going to talk a little bit this evening about how your diet and your lifestyle can interact with your genes this is called nutrigenomics how your diet and/or lifestyle can change the expression of your genes this is called epigenetics and this is really important is very important because it helps us understand how we can design a diet and lifestyle strategy to help us age the best way that we can so this is your metabolism it's very complicated and there are thousands of metabolic pathways just like this inside each and every cell inside each and every organ in your body and these metabolic pathways are what is allowing each organ in your body to do its function whether we're talking about your immune system and fighting off an infection or we're talking about your heart being able to pump blood throughout your body and give all sorts of goodies to various organs including your brain so it's your metabolism and your metabolic pathways that allow you to be alive they are running you essentially and these metabolic pathways many of them require micronutrients as cofactors which means they need them to function properly micronutrients are about 30 to 40 essential vitamins minerals and amino acids and fatty acids and many of these about 22% of all the enzymes in your body need and micronutrient as a cofactor to work properly so micronutrients we get from our diet and there have been recommended daily allowances RDAs that have been set to ensure that we get at least the adequate amount of these micronutrients to make sure that we're running most of these metabolic pathways okay most of the time but not all the people are meeting the RDAs for example magnesium 45% of the US population does not meet the requirement for magnesium which is between 350 milligrams to 400 milligrams a day depending on your if your male or female and magnesium is found at the center of a chlorophyll molecule chlorophyll give plants their green color so green plants are high in magnesium spinach kale these are all very high in magnesium magnesium is required for over 300 different enzymes in the body including the enzymes that are important for using and producing ATP you actually cannot use ATP unless there's a magnesium bound to it so if you're not getting enough magnesium this is impairing a lot of metabolic pathways in your body because ATP is the energetic currency of the cell in addition to that magnesium is required for enzymes that repair damage to your DNA it's required for enzymes that are important for making connections between neurons which is how your neurons communicate with each other and how we form a memory so magnesium is hugely important for many different processes in the body but as I mentioned 45% of the population is not getting enough magnesium and to complicate things even more we're all different so you and I we all have the same genes but we have different versions of those genes they're they're called gene polymorphisms so gene polymorphisms refers to just a single change in one nucleotide in the DNA sequence of a gene that can alter its function gene polymorphisms make us members of a group people with brown hair and brown eyes or people with blond hair blue eyes so these these alternative forms of genes can give us a certain phenotype like hair color or eye color but they can also give us a disease risk they can make us more susceptible to Alzheimer's disease or less susceptible to Parkinson's disease and cancer they can also change the way our body metabolize and use micronutrients vitamins minerals and macronutrients like fat as well as the way our body can inactivate certain xenobiotics which are foreign to our body they're chemicals that are found in the environment that are not normal to our body and that could potentially even cause cancer so I'm going to talk a little bit about gene diet interactions in this first part of my talk back to the magnesium so I mentioned 45% of the population does not meet the adequate requirement for magnesium well there's a pretty common gene polymorphism in a gene called TRP m6 and this gene is important for transporting the magnesium that we get from our diet from outside of the cell to inside of the cell so it plays a very important role because there's 3 over 300 different enzymes in the body that are using magnesium people with this particular gene polymorphism don't do it as well so there magnesium is not getting inside the cell as well as people that do not have this gene polymorphism in fact people with this gene polymorphism that have magnesium intake below 250 milligrams a day have a two-fold increased risk of type 2 diabetes so you combine that with eating a diet that's high and refined sugar low and micronutrients and it's sort of like a you know ticking time bomb for type 2 diabetes but there's a simple solution you can eat your greens about two cups of cooked spinach have around 312 milligrams of magnesium which is almost meeting the daily requirement so not only are you getting your magnesium but you're also getting folate which is very important for making new DNA you're getting vitamin k1 which is important for blood clotting you're getting lutein and zeaxanthin which are important for protecting the rods and the cones and your eye they play a role in preventing age-related macular degeneration so in your greens and you're getting fiber which is really good for your gut microbiome which is regulating all sorts of things including your immune system brain function so eating your greens is really like just eating a whole bunch of really good things that are good for all these you know different biological processes in your body gene polymorphisms also change the way we metabolize certain types of fat so there are different types of fat there's monounsaturated fat which is hi in olive oil avocados nuts there's polyunsaturated fat which is found high in fatty fish like salmon mackerel herring and also high in nuts and then their saturated fat which is found in dairy products cheese butter and fatty meat like pork well there's certain gene polymorphisms in a very cottagey called PPAR gamma P P R gamma is a master regulator of fatty acid metabolism and also of glucose metabolism it regulates it increases lipid metabolism increases atopy Genesis in adipose tissue it increases insulin sensitivity and muscle tissue and in the liver it increases something called gluconeogenesis which is how your body makes sugar when you don't give it a precursor the carbohydrate to make the sugar well a certain gene polymorphism in this gene changes the way it interacts with different types of fat and people that have it if they have a very low poly and monounsaturated fat intake and a very high saturated fat intake they actually have a much higher risk of being obese and type 2 diabetic but when their fat content comes mostly from mono and polyunsaturated fat and to a lesser extent from the dairy and the fatty red meat like pork they have a normal type 2 diabetes risk in the background of all other food intake so people with this particular gene polymorphism it's probably better off for them to make sure their fat sources are coming from fatty fishes nuts avocados olive oil as opposed to getting it from dairy and butter cheese things like that also there are very common gene polymorphisms in a gene that help inactivate certain compounds that are formed when you cook meat at high temperatures so any meat fish chicken red meat anything that's you know made of protein when you cook it at a really high temperature like when you fry it or when you barbeque grill it what happens is the proteins the amino acids in those proteins interact with carnitine and sugar and the high temperature and they form something called heterocyclic amines heterocyclic amines can form carcinogens in the body and this has been shown in you know dozens of animal model it's been shown it's been associated with cancer in humans but the good news is humans have a gene that can inactivate these heterocyclic amines so that's really cool if you want to cook barbecue your meat grill your meat your body can take care of that your body can handle it it's got a gene called NAT - that can inactivate these heterocyclic amines by adding a compound on to it called n acetyl an NS eel group gets added on to this heterocyclic amine becomes inactive and therefore it cannot form something that is carcinogenic in the body however people and there are very common gene polymorphisms I've seen them quite often that people have a very slow activity of NAT - and so when they're eating a very high volume of meat that is fried or BBQ grill you know every day you know there's certain heterocyclic amines that will not get inactivated and they can become carcinogenic so the bottom line is if you have these gene polymorphisms and the NAT two genes probably you're better off baking your fish baking your chicken not barbecuing you know four times a day and not pan frying your your meat you know four or five times a day so and I think this also explains a lot of the complexities in the clinical trials and nutrition where there's been a lot of studies that have linked for example eating cooked meat with cancer and there's been studies showing no it's not linked and you know I think that as tools become cheaper and we start to look at different gene polymorphisms we're going to start to sort of tease out this information and go oh it's those people with this certain gene polymorphism that can't inactivate that stuff that can form a carcinogen that are more susceptible to cancer when they eat cooked meat and the people that don't have it well they can eat the cooked meat because their bodies can handle it vitamin D they're also very common gene polymorphisms in vitamin D vitamin D despite its name actually gets converted into a steroid hormone and it regulates over a thousand different genes in the human body just to give you an idea that's about roughly 5 percent of the protein encoding human genome it's a lot of genes so the primary source of vitamin D is you beebee radiation from the Sun which hits your skin and you convert something in your skin called 7d hydro cholesterol into vitamin d3 a lot of processes are regulated by this so for example if you have aging so aged people cannot do this very well skin color so melanin which protects us from the burning rays of the Sun also prevents UVB from allowing us to convert 70 hydro cholesterol into vitamin d3 also where you live latitudes so depending on where you live not so much of a problem here in Ocala but in more northern United States in northern latitudes you don't need you can't even make vitamin D you know six months out of the year so lots of different things that can regulate the ability of your skin to make vitamin D once you make vitamin d3 in the skin it's it's given it goes into the bloodstream from there it goes to the liver where it's converted into 25 hydroxy vitamin D and then to the kidneys where it's then converted into active steroid hormone well there are common gene polymorphisms in the gene that encodes an enzyme called C Y P 2 R 1 and this enzyme converts vitamin D 3 into 25 hydroxy vitamin D 3 which is the major circulating form of vitamin D and this this polymorphism enables or it basically changes the function of this enzyme so that's not doing it very well so you're not actually converting vitamin D 3 into 25 hydroxy vitamin D very well and people with this gene polymorphism have a two-fold higher risk of vitamin D deficiency they have a higher all cause mortality so they die sooner from all sorts of non accidental diseases like cancer neurodegenerative disease cardiovascular related diseases then people that don't have this gene polymorphism and they also have a two-fold higher risk of multiple sclerosis so lots of you know increased disease risk for people that have this gene polymorphism most likely because they never get their vitamin D levels tested and don't realize oh I'm vitamin D deficient even though I'm supplementing with a vitamin d3 I'm still not making enough of the active form of vitamin D which is the steroid hormone so you can actually get your blood levels tested and and I highly recommend that I think that getting your vitamin D levels measured and tested is very important to do for all people of all ages the national endocrine society considers vitamin D deficiency to be below blood levels of 25 hydroxy vitamin G below 20 nanograms per mil considered to be inadequate at levels below 30 nano grams per mil and adequacy is considered somewhere between 30 and 60 nano grams per mil so there's a real sweet spot in terms of how much vitamin D you want you don't want to be deficient you don't want too little but you also don't want too much and studies have shown meta analyses have shown that people that have blood levels of vitamin D between 30 and 60 nano grams per mil have a lower all cause mortality so too much vitamin D not good too little not good around 1000 IU's of vitamin D per day can raise blood levels by five nanograms per milliliter in people without that gene polymorphism people that have the gene polymorphism in the Cy p2 are one gene may actually have to take much higher dose of vitamin D but you won't know that unless you get your blood levels of vitamin D measured vitamin D does regulate the aging process so these these mice here are the same age the mouse on the right has had normal levels of vitamin D throughout its four months of life so far and the mouse on the left has been genetically engineered to not be able to respond to vitamin D so it's essentially vitamin D deficient and these are the same mice for months later so vitamin D deficiency dramatically accelerates the aging process in in mice so it's not only aging the skin and no the hairs falling out but the organs are also aging faster so you know not getting vitamin D can cause a rapid aging phenotype and like I said there have been studies have shown that people with gene polymorphisms in vitamin D related genes like cyp two are one that have lower levels genetically have lower levels of vitamin d3 because their body isn't converting vitamin D into the active steroid hormone very well they have a higher all cause mortality so I'm going to talk just briefly on some of the research that I've been at Children's Hospital that has to do with vitamin D so I found that one of the genes that vitamin D is regulating is a gene that encodes for an enzyme called tryptophan hydroxylase and this is the rate-limiting enzyme in the production of converting l-tryptophan into serotonin most people view most people here probably think of serotonin as being a neurotransmitter or that regulates mood the way we feel you've probably heard about it in the popular media but it actually does so much more and what's really interesting is that humans have two separate tryptophan hydroxylase genes T pH 1 and T pH 2 and these genes are found in different tissue tissue so tryptophan hydroxylase one it's predominantly found in the gut and it converts all the tryptophan from the protein you eat in your diet to serotonin in the gut and the serotonin made in the gut does not cross over the blood-brain barrier and get into the brain serotonin in the gut plays a very important role because platelets in your blood take it up platelets can't make their own serotonin but they need it because serotonin plays a very important role in platelets aggravating together which is important for when you injure yourself you have a wound you cut yourself your platelets aggregate you want to make sure that you have clot there so that you don't you know bleed out so the serotonin made in your gut plays a very important role in making sure platelets are getting their serotonin however too much serotonin in the gut actually causes gut inflammation and I'll get to that in just a minute the other gene that humans have is the same gene but it's just a little bit different a little bit of a different sequence and it's in the brain and it converts all the tryptophan that gets into your brain into serotonin and in the brain serotonin is doing a lot of things which I'll talk about in a minute but what my research identified is that these two separate genes the one in the gut and the one in the brain both have a little telltale sequence in them that vitamin D when it binds to the vitamin D receptor is able to recognize and what was very interesting was that the gene and the gut contained a sequence that's consistent with turning that gene off making sure that not too much of it's being active so that it's not doing its function very readily whereas the one in the brain tph - had a sequence consistent with activation for turning on so that the trip took more tryptophan is being converted into serotonin in the brain and since I've published this paper early in 2014 another independent group out of University of Arizona has validated some of this work and have shown very elegantly biochemically that vitamin D does indeed activate tryptophan hydroxylase - it increases mrna and you're making more making theoretical a should be making more serotonin in several different types of neurons so what my research identified was that vitamin D may be regulating serotonin production in different tissues in opposite directions in the gut it could be turning down that gene so you're not making so much serotonin in the gut which is really important because too much serotonin in the gut causes gut inflammation because it activates a variety of meat immune cells in the gut and causes them to proliferate and make more and it's been shown in several different mice mouse models that have for example colitis or irritable bowel syndrome when they delete that gene tph one in the gut and prevent it from making serotonin the dis ameliorates the symptoms of colitis so the colitis goes away and the GI inflammation resolves so vitamin D may be important for turning that down in the gut and turning it on in the brain and you want to have serotonin in the brain you want to make serotonin in the brain so vitamin D may be doing two separate things to two separate genes in different tissues and it's regulating in opposite directions so like I said serotonin is doing so much more in the brain it's not just regulating mood but serotonin also is very important for impulse control for social behavior for mood for anxiety and memory many different studies have been done by a variety of behavioral scientists and neuroscientists that have shown that you can actually take a person a normal person and you can deplete them of the tryptophan that gets into their brain and now remember tryptophan has to get into your brain to make serotonin you can deplete them of their tryptophan and what happens is people become very impulsive their long-term thinking shuts down they get anxious they get depressive so you know all these these thing these processes are sort of going wrong when you can't make serotonin in the brain and I published a paper in early 2014 that related the vitamin D regulation of serotonin to autism and I gave several different reasons for this which I don't have time to get in tonight tonight but I just want to talk about a couple of them one has to do with the fact that during early brain development serotonin is actually what's called a brain morphogen because it actually shapes the structure and the wiring of the brain it tells neurons in the developing fetal brain where to go and it tells them what types of neurons to become and it's been shown multiply multiple different methods by deleting genes that are important for producing serotonin also by pharmacologically inhibiting serotonin during early fetal development and animals that this disrupts the structure and the wiring of the brain when you can't make serotonin so if you know a an infant which is a developing fetus which is entirely dependent on the maternal levels of vitamin D meaning it has to it's relying on whatever levels of vitamin D its mother has and if vitamin D is very important to make serotonin in the brain then if a mother is deficient in vitamin D it's possible that developing brain isn't getting enough vitamin D to activate that gene that's very important for making serotonin in the developing brain and it's possible that in combination with other gene polymorphisms that regulate serotonin because those have been shown to be associated with autism that that's the perfect storm where you have someone who's already genetically susceptible to low serotonin on top of that they're not getting their vitamin D they're not getting the nutritional input to activate the serotonin pathway that may be sort of the perfect storm for abnormal brain development I also related this to the other tph enzyme in the gut not only is it made in the gut but it's also made in the placenta so maternal Auto antibodies have been mothers of autistic children are four times more likely to have Auto antibodies in their blood against fetal brain proteins and it's been shown experimentally in monkeys that if you cause an autoimmune response against these fetal proteins in the brain and the developing fetus that monkey's brain structure is abnormal it develops abnormally and monkeys actually develop sort of like autistic like behaviors and a lot of this work has been done out of UC Davis and so what I'm thinking is possible because tryptophan can be converted into serotonin by T P h1 in the placenta it can also be converted into something called kynurenine into placenta which is essential to make something called T regulatory cells T regulatory cells are a type of immune cell that regulate your body's autoimmune response so they basically when you make more of those they tell your body okay you know the tissues in my body or mine don't attack it this is a big problem when you have a developing fetus because your body goes whoa what's that that's foreign get rid of it get rid of it and having these T regulatory cells or what tell your body no don't leave it alone supposed to be here so it's really important to have those T regulatory cells well what's really interesting is that tryptophan has it binds to this enzyme t ph one three times tighter than it does i to this other enzyme i do which is really important for making kind yearning so it's possible that if you don't if you're getting if you're not getting enough vitamin D which has been shown you know to maybe which we think represses that gene that's possible that you're not getting enough these T regulatory cells because too much of have to having too much expression of C pH one may act as a tryptophan trap and may cause all the tryptophan to be converted into serotonin in the placenta and not enough of it is forming kinda raining and these T regulatory cells and that could lead to an autoimmune response and potentially abnormal brain development and this has been shown in mice which have been deleted they have deleted this enzyme I do and therefore they cannot form conure anine T regulatory cells drop and female mice that then become pregnant have such strong autoimmune response if they actually abort the fetus um so this is all research that needs to sort of be teased out and done but it's a potential hypothesis to be tested and there's huge relevance for prevention here because all you really need to do is make sure that a mother that's you know going to be expecting have a child on get her vitamin D levels tested make sure she's getting enough vitamin D and you know vitamin D cost a penny a pill so it's a really simple solution to take a vitamin D supplement make sure you're within that adequate range of vitamin D alright so that was autism that was some of my research that I've done with Bruce at Children's Hospital in Oakland and I did a follow-up study um sort of adding on my previous work on how vitamin D increases serotonin to include omega-3 fatty acids the amino mega three fatty acids I cosas pentanoic acid EPA and Doka hexanoic acid DHA and how these also may relate to serotonin and to brain function to ADHD impulsive behavior bipolar disorder schizophrenia a variety of brain dysfunctional disorders so I mentioned how vitamin D is important to make serotonin in the brain well EPA is very important for releasing serotonin from a presynaptic neuron because it inhibits something called e two series prostaglandins which inhibit the release of serotonin from presynaptic neurons so if you in if you take if you have e enough EPA it will make sure that serotonin is being released from a preceptor synaptic neuron DHA the other marine omega-3 fatty acid that's found in fish is very important for the serotonin receptor which is how serotonin exerts all its functions you have to have serotonin binding to its receptor for in order for us to to feel anything so the serotonin receptor the structure of it depends on having a certain fluidity to a neuronal cell membrane and DHA plays a very important role to that fluidity of the cell membrane and it's been shown that when DHA is when there's DHA deficiency that neuronal cell membrane changes and so does the serotonin receptor so serotonin is very DHA is very important for serotonin to bind to that serotonin receptor and I talked about in this paper how low vitamin D low EPA and low DHA intake so if you're not eating your fish you're not getting enough vitamin D vitamin D salsa fountain fish then you may have you know problems with serotonin production and function and in combination with gene polymorphisms in serotonin receptors share certain transporters genes that make serotonin like tryptophan hydroxylase - which have all been linked to a variety of neuropsychiatric disorders that people on top of that if they're not getting enough of their marine omega-3 fatty acids are not getting enough of that vitamin D they may be having serotonin dysfunction in their brain and so you know making sure people get enough fish or taking a fish oil supplement taking a vitamin D supplement are pretty simple solutions to at least help alleviate the part that we have control over which is not the genetic part but the part that we know certain dietary factors can regulate these different biological processes that are controlling serotonin so what's the take-home here I just told you a dumped a bunch of information on you told you all about these gene polymorphisms all these cool ones well I want to know if I have them ones with men you know that's affecting that magnesium or the ones that's affecting you know different types of fat or my heterocyclic amines or my vitamin D well there's a company called 23andme and 23andme is a consumer you know available to consumers it costs around $199 they send you a kit you get the kit you spit in a tube and after you spit in the tube you send it to back off to their lab and they'll sequence a variety thousands of different gene polymorphisms that you have you know your DNA and they'll tell you some things about it they don't really give you in-depth health reports but there's another tool that's called premies EA's that you can use cost about five dollars and they interpret many of these gene polymorphisms they in scientific terms sort of tell you oh well this is associated with this this is kind of what this may mean but in addition to that I've developed a tool that I'll be releasing very soon that also lets you export your 23andme data into my tool and it will also tell you what it means and what sort of dietary solution or environmental lifestyle solution to that may help you deal with this gene polymorphism and I'll be releasing that on on my website found my fitness comm and also my newsletter you can sign up for I'll be talking about when I released that and I also talked of I explain how to use 23 million premies and things like that if you're interested okay so next part of my talk I've been talking all about how these different changes in the sequence of DNA make us all different different but also make us members of a group so gene polymorphisms make us different but also make us members of a group now I'm going to talk a little bit about changing how much of a gene you make we call that changing the expression of your genes so different factors in your lifestyle different dietary factors different micronutrients stress how much sleep you get how hot you are how much you exercise all these things can change certain factors epigenetic factors that can sit on top of your DNA and they can turn a gene on they can make it more active make it do what it's supposed to do so you're doing more of it or they can turn a gene off so that the gene is not active it's there but it's almost as it as if it was not there because it's really not doing the function that it's normally supposed to do and like I said these are regulated by our environment by what we eat but how much we eat or how little we eat how much stress were under but the really interesting thing about epigenetics is that these epigenetic marks they actually hitchhike on to the sperm DNA and the egg DNA and they can be passed on to the next generation they can be passed on to your children and even to your grandchildren in some cases so I would highlight sort of a really good example of this that was done in animals was done in mice so this was done a few years ago the study came out of Australia and researchers fed male mice a very inflammatory diet it was a diet that was high in corn oil high in sugar is terrible diet the mice became obese and they got you know they got type-2 diabetes so they became insulin resistant big surprise most of us know that obesity is associated with type 2 diabetes but what was really interesting is that these male mice had female offspring that were fed a normal diet and those female offspring did not become obese but they developed type 1 diabetes so why is that why did they were fed a normal diet why did they develop type 1 diabetes well it turns out that this diet that's high in flam Ettore diet that these male mice were fed caused an epigenetic mark called a methyl group to go on top of the sperm DNA next to a gene that it's important for creating insulin in the pancreatic beta islet cells turn it sat on top of that gene it turned off so I wasn't working even though it was there and that sperm DNA then made up a new Mouse and so the new female Mouse had this gene that had this little mark sitting on top of it that was turning it off so it this the female Mouse was unable to make insulin and that's type 1 diabetes so pretty pretty interesting study and you know dozens and dozens of studies have been you know published since then have come out showing mechanistically certain dietary factors environmental factors being exposed to stress early on these things can be passed on to offspring that haven't been exposed to that stress like a loud noise you know combining it with a smell for example you know then you have a female I mean then you have an offspring and that animal then all of a sudden hates the smell of whatever it is but it's never been exposed to it why does it get anxious so there's things that are regulating some you know genes and sperm and also an egg DNA they're getting passed on so what about humans very recently in fact earlier this month in December a study was published in the Journal of Cell Metabolism where and some investigators wanted to sort of look at humans to see if they could see you know if any of these epigenetic changes were happening in humans so they recruited a very small population of overweight and obese men and they took a sample of their sperm DNA and they compared it to sperm DNA from aged matched lean men and what they found was that the sperm DNA from these obese men had all sorts of epigenetic marks these methyl groups in places that weren't there in the lien men it was totally different in fact over 9000 different jeans were different and this is this is called the methylome kind of a complicated science e word but really it's just these epigenetic factors were different in over 9,000 different genes so these men then underwent bariatric surgery so they lost ton of weight like that and their sperm DNA was collected one week after and then one year after the bariatric surgery and what was very interesting about the study was that one week after the surgery the epigenetic marks in the sperm DNA had changed in over 1500 genes and a year later it had changed in over 3,000 genes and it was beginning to look more like the signature of a lean person so just the weight loss itself totally changed all these epigenetic factors which again like we just talked about changes function of genes like in the case of not making enough insulin in your pancreatic islet beta islet cells it changed it in sperm DNA so it's a very provocative study that suggests that this also may be happening in humans as well you know so epigenetics is a very interesting field you know it's also been shown to be associated with the way we age and I'm not going to talk about this tonight but there are unique epigenetic signatures that happen when we age and it's very interesting because they're so correlated to age that scientists can take a blood cell out of you and not know your age they can don't even see you just they get the blood sample and then they can identify your age plus or plus or minus so they can look at just a blood cell and look at these epigenetic marks on your blood cell on your DNA in your blood cells and go oh that person's probably around 55 years old and they'll be pretty accurate 96% accuracy actually but I am going to sort of shift gears from epigenetics and I just want to touch on some of my clinical research that I've been doing at Children's Hospital so we were talking about obesity and how obesity can have negative effects on sperm DNA well it also has negative effects on the individual itself so obesity increases the risk of cardiovascular disease it increases the risk of type 2 diabetes but what most people don't realize it also dramatically increases the risk of most cancers in fact by twofold it also increases the risk for neurodegenerative diseases like Alzheimer's disease and obesity you can take seven years off the lifespan and in extreme morbid okay stat cases it can take 14 years off lifespan 14 years is a long time that's a long time to take off your life just from being morbidly obese so the obesogenic diet as I like to call it consists of it's a diet that is very low in vegetables it's very low in micronutrients and in fiber and it's very high in refined carbohydrates it's very high in processed foods packaged foods you know foods and cans breads you know just refined processed foods you know and also processed needs so this type of diet I mean there's all sorts of consequences was having a diet like this and it is extremely complicated and I'm not going to get into any of that stuff I'm just going to totally simplify it here but a diet like that causes a lot of damage in the body for multiple reasons and this damage that's generated mostly from your mitochondria they're not working properly they're leaking out something called reactive oxygen species it's activating your immune system which you're making something called reactive nitrogen species and these things are damaging your cells the lipids in your cells the proteins in your cells the DNA in your cells which is then causing more active immune activation and this is vicious cycle of more and more damage I'm and like I mentioned it it damages your DNA and it can cause double-stranded breaks in your DNA and these double-stranded breaks are a biomarker for aging they're a biomarker for cancer and so that what they do is they cause cells to become senescent cells which means the cell just it's not dead but it's not alive it's just kind of sitting there and it's secreting bad stuff that's causing more inflammation or it can cause cells to become abnormal and these abnormal cells can eventually lead to cancer so it's really a biomarker for aging in cancer and I've been studied i've been looking at double-stranded breaks in in obese people but the way I'm measuring it so this break in your double strain in your DNA it's a double-stranded break which is the worst kind of break it's really really hard to repair a double-stranded break because it's happening in both strands of your DNA at the same time the way that I'm measuring it is by measuring something called gamma h2ax which is what happens the first signaling event that happens when your DNA strands break is that your this protein called histone a 2x becomes phosphorylated that's called gamma h2ax and it magnifies over like kilobases of DNA and the reason this happens is because it's like a molecular beacon it's a signal signaling to your cells going hey hey there's a problem here we got damaged we need to fix this now and so this serves as a signal for all these repair proteins all these you know things are going to repair that damage they get recruited to that site of damage and they fix it up if they can in some cases the damage is too much and they can't do that but so this serves as a marker for double-stranded breaks and I'm measuring this in people blood cells from people that are obese overweight lean and I'm looking at this gamma h2ax as a marker of DNA damage and what I'm finding is that people that are overweight or obese and have a BMI of 28 and above have a much much higher level of these double-stranded breaks in the DNA and their blood cells I'm looking in their white blood cells compared to people that are linked significantly higher DNA damage which is really bad because DNA damage like I mentioned it's a biomarker for aging DNA damage is associated with shorter telomeres which is also a biomarker for aging it's associated with increased cancer incidence a variety of different things DNA damage is not good so I'm seeing that there's a lot more of this damage in blood in white blood cells from people that are obese and in addition to that I'm looking at the ability to repair that damage so I induce a known amount of damage in these people by giving them they're giving their blood cells ionizing radiation and then I allow the blood cells to recover like for six hours and see if it can repair that damage so I'm looking at that and I'm also looking at the mitochondrial function at the same time to see you know how the mitochondria are performing when you damage them and when you're looking at versus lien population we're seeing all sorts of really interesting things I'm not going to discuss tonight but the bottom line here is that what you eat does much much more than satiate your hunger it is providing your body with the right vitamins and minerals and essential fatty acids and essential amino acids that are important for running all those complex metabolic processes that I started my talk with and these vitamins and minerals and fats and proteins are also interacting with our genes you know so there's a complex interaction going on so you want to make sure you are feeding your body the right kinds of foods so that you can age the best way you can so that you can make sure that you stave off as long as you can Alzheimer's disease cancer you know cardiovascular disease and things like that so this is a kind of a snapshot of my my diet I eat a lot of fish I like to make homemade chicken bone soup and smoothies with kale and spinach and lemons and apples and with that I'd like to say thank you for listening and I'd like to thank my mentor Bruce Ames and Jay Ramsey who just recently graduated from UC Berkeley phenomenal student that's done almost all the work that I've been doing on DNA damage and also Darryl Chow who's a technician that's been working with me he's also phenomenally we've been helpful in doing a lot of DNA damage work some questions and someone's going to bring a mic around okay either on your own shirt I'm not looking for a shortcut but if I take a vitamin with vitamin D and the magnesium and eat more spinach will I continue to be healthy I think I think eating more spinach is really good and taking a vitamin D pills really good but also measuring your blood vitamin D levels is important because like I mentioned you know people have polymorphisms that make it so even if they're taking a vitamin D pill they're still not getting enough vitamin D and they wouldn't know that unless they measure their vitamin D levels okay on your data with autism patients there's been there's been some data coming out about infections on pregnant mothers increasing the risk of autism when in your patients were you evaluated the vitamin D did they also look for infections during pregnancy to see that was a concomitant factor as well so that the research that I so the question is what did I look at infections to see if infections were also quality with autism and I just want to clarify that this was not clinical research so I did not have any patients with autism or mothers of autistic children that I specifically was looking at I was referring to with some of the autoimmune autoimmunity research I was referring to studies coming out of UC Davis where they had done studies where they caused female monkeys to have a very potent autoimmune response and I think it was kind of like they were they were giving him some sort of adjuvant thing that was causing them to have a very potent autoimmune response and that was then the the mother's immune system was in attacking fetal brain because it was actually getting across the blood-brain barrier and attacking fetal brain proteins and that was causing abnormal brain development but but what's what's interesting is that mothers of autistic children have you know four times more likely to have in their blood even and still Auto antibodies against fetal brain proteins like you shouldn't have as a female antibodies in your blood against brain proteins so yes they're in the in the white shirt sitting right next to yes you right there there I'm sorry could you repeat the question Oh vitamin D sublingual uh-huh I'm not familiar with sublingual vitamin D I'm sublegal with I mean I'm familiar with sublingual vitamin b12 b12 which is important yeah vitamin b12 because you know as you're aging as you age is become you become less capable of absorbing vitamin b12 and so sublingual by vitamin b12 can bypass some of those deficiencies but vitamin D as you're older is important to supplement with because you can't make it in your skin very well in fact a 70 year old makes four times less vitamin D than therefore more for more 25 year old self so you may think well I'm living in Florida I'm out in the Sun but if you're 70 years old you may not be getting as much vitamin D as you think you're getting okay right there in the I think it's purple or dope Oh got it okay yeah I wonder if what your view is on when and if we can merge the medical community and government policy more towards nutrition I'm with you on that one yeah I I don't know you know I'm definitely more I'm excited about preventive medicine I'm excited about you know the more we understand about nutrition and the more we understand about how what an important role plays in the way we age and having the medical community adopted and you know the larger committee itself adopted it's going to be nothing but good maybe we should get someone so we get someone over here yeah right there this is rather personal but we have a granddaughter that wants to be you and she starts undergrad next year and probably pre-med but would you have a recommendation on what she should be targeting for maybe even a school for post-grad what I like to tell people is it's best to target a lab if you're going into the sciences I mean so if you're going into the sciences it's best to target a lab that's doing research that you're interested in and also for for someone who's a young developing budding scientist in my opinion I think one of the most important you know aspects of training is having someone who is hands-on earlier in your career because you need to learn you need to learn how do you use different tools at your disposal to be able to answer interesting biological questions and if you never if you're kind of just left to like your own you know you know to do whatever you want because you're in a really really big lab and people don't have time for you you won't get that really fundamental training I think is so critical for young scientists now as they continue on in their career post graduate then I think it's more important to have freedom but I think that early on finding a lab that you're interested in and finding one that you're going to have a mentor that's a good mentor that's hands-on it's going to give you time and attention that would be my advice yes sir in the red coat blazer you mentioned two or three self tests that you can do do those include the vitamin d3 test and if not how do you get your d3 tested great question so no they do not include the vitamin d3 test so the the 23andme is a test that measures your genetic polymorphisms vitamin d3 is pretty standard I think any clinician any any physician if you ask them will measure it in fact most of them should just be measuring it anyways but if you don't if you don't have a physician there's companies online that will do it like wellness FX is one they'll allow you to but you can look at a variety of different in biomarkers and micronutrients vitamin D is one of them and there's also soon to becoming a kit that you can you know at home have on your countertop or you were going to be a little cartridge where you finger prick your blood and then you can measure your vitamin D levels and also other hormones that's coming soon I think yes right here on the front oh we got someone else in the back first okay when dr. Ames was here he told us his team was developing this wonderful nutritional bar that sounded amazing I want a case of them are they out yet they're not out yet they are not commercially available yet they're still they're still in the research part but but they're working hard to get those on the market so I think we had someone in the front here um it seems like the autism has reached epidemic proportions in what maybe the last 10 15 20 years something has to be happening if you think that the mothers are affecting the new board they're their child that's in utero ah has anything been researched and determined on the environment genetically modified foods possibly glyphosate that's being sprayed on wheat crops yeah so you're absolutely right autism rates have climbed by five hundred percent since the 1970s you know one in 88 children have autism which is just it's just it's it's growing like exponentially it's a lot I don't know much about you know these these environmental pesticides and things like that but I do know that at the same time that autism has been rising vitamin D levels have been declining because of people that are now wearing sunscreen because of fear of skin cancer people now inside kid Nina playing playing video games TV use technology so as the same time that autism is rising vitamin D levels have been dropping so there's sort of this interesting correlation there that's been going on and I do think that the the effects of vitamin D on regulating serotonin and very important role serotonin plays in early brain development is is quite compelling we have time for one more question okay we got here in the white shirt you talked a lot about under utilization of like save not getting enough vitamin D but you also talked about the problem with over consuming micronutrients so where is the practical solution for like most people here and trying to correct for not getting enough or getting too much and in respect to that question what do you think of a multivitamin the controversy of use and not using that okay so this is a great question the first part of the question is will you know too much vitamin D is not good too little is not good so how do you know how much vitamin D you should be taking and you know the answer to that is obviously based on the information you're exposed to so getting exposed to talks like this where you have experts coming in telling you well between you know getting your blood levels of vitamin D measured is very important and you should have blood levels between you know thirty to sixty nanograms per milliliter and we know that taking 1,000 IU's of vitamin D a day raises your blood levels by five nanograms per mil so you can sort of calculate how much vitamin D you need to supplement with you should also be able to supplement and then after supplementing measure your levels again so I think that's obviously the best approach that you could take is by getting a blood test for vitamin D supplementing with vitamin D and you know seeing if that's actually raising your levels of vitamin D and then the second question is what do I think about the multivitamins and the negative versus positive effects that multivitamins may be having and I actually address this in one of the videos that I put out there on the Internet and it's called the rebuttal to the vitamins are bad and it's really basically there's very there's lots of complications in clinical trials in nutrition clinical trials using micronutrients many many many of the studies do not measure anything mostly because it's too expensive so they give people a vitamin D supplement they give them a multivitamin that has 200 IU's of vitamin D in it you know and then they don't measure anything in the blood and then they're looking at some outcome clinical outcome of X Y or Z and they say oh this clinical outcome of X Y or Z isn't affected so you know there's probably no effect that vitamin D or the multivitamin has on the opposite end of the spectrum when you give someone a high dose of certain vitamins for example folic acid which is the oxidized form of folate that folate plays a very important role in making a precursor for your body to be able to make new DNA so every time you make a new cell whether that's the cell in your gut or your skin your heart your liver you need to make new DNA which means you need folate because you need to make this precursor for a demian nucleotides that it's required for um but guess what else makes new cells cancer so if you give someone who already has for example a colon polyp colon cancer polyp a bunch of Volek acid that's like fueling the cancer to grow more because you're like here's more of those precursors you like to make more cells but if you give that same you know dose I guess folic acid is not the best example because too much of it's not good but if you give it to people that don't have cancer it doesn't cause cancer so it's kind of it all depends on the the trial designs on the study designs on and and they're just for reasons of funding they're not done well you know it's it's hard to find a Clinical Nutrition study that is done properly that has done you know well-done controls that looks at blood levels of whatever they're measuring or looks at blood levels of other biomarkers and also that looks at genetic so there's there's an unused a huge huge trial that's going to be done on vitamin D and they're going to look at and like thousands and thousands of people they're going to look at supplementing with 2,000 IU's a day in a variety of different genders and ages and they're going to look at they're going to measure blood levels of vitamin D they're going to measure other proteins that regulate vitamin D and they're gonna look at gene polymorphisms and I'm going to start to look at clinical outcomes and I think that's the way we should be doing clinical trials in nutrition we should be looking at all these different factors right now it's too expensive I mean getting I'm doing clinical trials I'm involved in clinical trials at the hospital in Oakland and you know getting blood measuring all these biomarkers these things cost a lot of money and so when you're doing a huge trial and you don't have that money to do that you sort of don't do it and instead you just look at a clinical endpoint so kind of a complicated answer but it was a complicated question now let's thank our speaker thank you

Channel: TheIHMC

Views: 330,980

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Id: wQZz5PklDB0

Length: 55min 43sec (3343 seconds)

Published: Wed Feb 03 2016