 So it's a pleasure to be invited here to talk about a subject that I've been interested in in the past 15 years when I Resigned as a chairman and professor of cardiothoracic surgery at Loma Linda University and devoted my time to restorative medicine where I try to reverse diseases with food and supplementation and And almost immediately after starting my practice in Palm Springs and subsequently Santa Barbara. I was testing for the APOE status of all my patients and became intrigued with the number of my patients who had heart disease who carried either heterozygous or Homozygous APOE for and so I've spent the last 15 years finding these patients who are often they find me and Designing a program testing them every three months with biomarkers cholesterol markers and I'm going to tell you today what we've come up with so far That's me. I Also run the International Heart and Lung Institute in Palm Springs, but our centers for restorative medicine are now in both Palm Springs and Santa Barbara Anyone who comes here doesn't think there's much controversy over what constitutes the ancestral diet Yet little if any attention is given to a diet that is compatible or complementary to the true ancestral genome true Approximately 30% of humans carry one or both copies of the apple lipoprotein e4 genotype The heterozygous apple e3 4 about 25% in this room carry that The apple e2 4 about 2% or the homozygous apple e4 4 about 2% sorry the 2% is missing The apple e4 genotype is common to the great apes. In fact, it is their genotype But only humans can and do carry apple e2 3 and 4 alleles The presence of the apple e4 has been associated with increased susceptibility to accelerated atherosclerosis Which is how I got interested in it decreased longevity susceptibility to infectious diseases and Alzheimer's disease by changing the way lipoproteins interact with cell surface receptors and Regulating brain amyloid beta peptides in the brain I'm going to leave that discussion to my esteemed colleague who will be following me in brief time However, I don't like to call this the Alzheimer's gene. In fact, I prefer my patients call it the fragility gene Because it affects so many systems that we are remiss to think that this is just affecting memory In terms of memory, however, there are statistics 3 4s carry approximately a two-fold increased association with the development of Alzheimer's disease While apple e4 4 may increase the risk of Alzheimer's dementia 8 to 20 fold depending on the study cited So there is a very powerful connection particularly in homozygos for force Now as many of you may not know Nigerians have the highest incidence of the apple e4 genotype of any studied population In fact, it is a huge percentage of their population Yet their incidence of Alzheimer's disease and other forms of dementia are extremely low age match and apple e matched African-Americans from Indianapolis have been significant have significantly higher LDL and small particle LDL's than their corresponding age match Nigerians and significantly higher rates of Alzheimer's disease Here have been two studies and I apologize. I didn't put the References I put references on everything else and somehow it missed but there are two studies done by the same group That have looked at this comparison and the comparison stands up in a small group study It was initially published and now in a much larger group study Now interestingly despite the increased association of Alzheimer's disease in African-Americans with apple e4 versus Nigerians what's striking in this comparison study is that elevated LDLC had the highest Association with Alzheimer's disease Regardless of apple e status in other words what this study showed in black Americans versus Nigerians that High LDLCs was the strongest predictor of Alzheimer's disease Regardless of that poe status and in fact the Nigerians who do develop Alzheimer's disease And there are a few small ones in fact have high levels of LDLC Now great apes carry apple e4 They have at levels of LDLC that are extremely low and even in captivity have not been shown to develop AD Perhaps the LDL connection is the missing link excuse the pun when carrying at the ancestral apple e4 Now I want to share with you a number of studies First on the first study is on apple e4 versus the other Genotypes in the effect of fats and then I'm going to talk about in general our strategies That have been studied for reducing the impact of the apple e4 gene The first study comes out of Spain The effect of dietary fat on LDL size is influenced by apple lipoprotein e genotype and healthy subjects This study involved 86 subjects. They went on a crossover diet for a month each They went on a high saturated fat paleo diet They crossed over to a high carbohydrate low fat diet a la ornish or Esselstyn and Then we're crossed over to a high olive oil Mufa Mediterranean diet with olive oil being used approximately one liter per week And you'll see another study About that by a similar group in Spain a little bit later on in the talk Now interestingly enough the LDL particle size was significantly higher in subjects with the apple e They call it the 4-3 genotype compared to those with apple e3-3 or 3-2 in the basal state So this is the first study to actually identify that there's something different About the four carriers that starts them off or as my friends in the audience you off With a higher resting level of LDL C Now fascinatingly the high saturated fat diet Increased the particle size in apo e4 subjects the most But after the carb low the high carbohydrate diet a Significant increase in LDL particle size was noted only in the apo e4 3 subjects But it had no effect or actually decreased LDL on the apo 3 3 individuals In other words the low fat diet which you would think would be extremely good for people carrying the apo e4 Had the reverse effect which I'll try to convince you why that is in a few minutes I think this is one of the most important things and anyone in this room can take out of this study is that number one Saturated fat made things worse and oh by the way a high carbohydrate low fat diet also made things worse So what are we going to do about that? This was their conclusion the hyper response of LDL C concentrations associated with the apo e4 Allial occurred only when the fat content in the diet varied and I'm sorry I put the same conclusion and there's the reference for you Now because of this we have focused our attention on keeping the small dense oxidizable particles of LDL as low as possible By a low animal fat high mono unsaturated fat high soluble fiber and resistance starch diet Over the years we've developed rules Everyone who I see in my office. I basically Write hand write these rules right above their apo e4 status first rule is limit animal fats and if I did a survey of Favorite food of apo e4's I Can usually spot an apo e4 by a food questionnaire because cheese is usually The highest or second highest ranked favorite food of apo e4's It is so consistent that I ought to publish a paper about it, but Four's love cheese and it's it's kind of like I tell them it's your kryptonite and You should stay away from your kryptonite Our studies over 15 years have found that dairy fats have the strongest correlation to the production of oxidized particles of LDL and That removal or drastically reducing them improves oxidized LDL levels rule number three and this is Actually the confirmation of the study. I just showed you Lowering triglycerides lowers oxidized LDL How do you do that? Anyone who's been to my clinic knows that we limit triglyceride production by lessening sugars fruits and seeded vegetables Seeded vegetables are not vegetables. They are botanically fruits and fruits contain fructose and Fructose are changed into triglycerides in the liver or converted into uric acid and My studies have shown that a incredibly limited fruit and seeded vegetable diet Is part and parcel with lowering your oxidized LDL Now shellfish are emphasized as the animal protein of choice if desired Owing to our observed small dense LDL lowering when these foods were added Particularly crab crab is incredibly effective at lowering small dense LDL's And I'll show you some studies about the impact of shellfish on cholesterol in just a minute We further minimize the oxidation of small LDL particles using generous amounts of polyphenol rich olive oil As well as the polyphenols and resveratrol Grape seed extract Turmeric and pomegranate seed oil and extracts You'll see this over and over again. I can't keep mentioning it The only purpose of food is to get olive oil into your mouth Now, why do I say this? There's some beautifully designed recently published trials looking at the Mediterranean diet and age related cognitive decline a randomized clinical trial Parallel parallel group randomized clinical trial of 447 cognitively healthy volunteers from Barcelona, Spain 50% were women mean age was set with 67 years of age when the study started Participants were randomly assigned to a Mediterranean diet supplemented with extra virgin olive oil one liter per week If that sounds challenging the average crete Uses or drinks about 32 gallons of olive oil per year My wife and I aim for a consumption of about a liter and a half of olive oil per week between the two of us and Usually we exceed that The second group had a Mediterranean diet supplemented with mixed nuts These were primarily walnuts with a few almonds and hazelnuts 30 grams per day Or a control diet, which was actually the American Heart Association low-fat diet These people were followed for six years. They had neuropsychological and memory tests of baseline and approximately five-year follow-up All cognitive composites significantly decrease from baselines in the control low-fat diet But changes from baseline of the global cognition composite were zero point oh five now. That's actually positive for the Mediterranean diet plus olive oil slightly negative minus zero point oh five for the Mediterranean diet plus nuts, but excuse me, but a Rather impressive zero point three eight cognitive decline for the controlled diet So my advice to my apoE4 patients has always been that the only purpose of food is to get olive oil into your mouth I'll probably say that one more time throughout the time Now what about fish oil in memory? This is a fairly recent study looking at RBC EPA and DHA the two primary components of fish oil as many as you know your brain is Depending on who you want to argue with 60 to 70 percent fat half of that fat is DHA the other half is interestingly enough arachidonic acid The best source of arachidonic acid everyone is egg yolk and liver, but egg yolks my preferred way to go Now this was the women's health initiative study And so this was a very good trackable group and these were extremely late Aged women at the time they were recruited At the time of enrollment the subjects were 65 to 80 years of age But if you can notice the mean age the average age was 78 years of age at the time of the initial MRI a Total of over a thousand women were followed for eight years Now in fully adjusted models a one standard deviation greater RP RBC EPA and DHA by the way serum fish oil serum omega-fat means Absolutely, nothing it tells us what you had for dinner yesterday RBC EPA and DHA index looks at the DHA and EPA bonded to red blood cells Since red blood cells stay in circulation for about two months of time This gives us a composite view for the last two months of what was actually Circulating in your system in terms of EPA and DHA So all those fish oil studies you read where serum omega-3 fats are measured Just please find the closest wastebasket or the trash on your computer and throw them away. They're absolutely meaningless Sorry for that editorial comment So DHA was marginally correlated, sorry The grip the index was correlated with a 2.1 cubic centimeter larger brain volume DHA was marginally correlated with a total brain volume while EPA was less so a One standard deviation greater omega-3 index correlated with greater hippocampal volume Which is where the rubber meets the road in memory Now the best part of this study is that comparing the Sorry wrong button Comparing the fourth quartile Versus the first quartile of omega-3 index in other words the highest versus the lowest Confirmed greater hippocampal volume in the highest versus the lowest so DHA in particular Is where you want to spend your money and your time in boosting these levels and My I didn't put it on the slide But we routinely measure this every three months and we in all of our Apple e4 as we try to achieve Indexes of 10 to 12 Normal is 8 So we actually super push this above normal Now how about shellfish and cholesterol this is one of my most frequent Comments about everybody knows that shellfish raised cholesterol Now much of this Data was generated many many many years ago When we could measure cholesterol levels in foods and we only could measure cholesterol But we could not measure the other forms of sterols And in fact shellfish have huge amounts of sterols that actually block and compete with this with the absorption of Cholesk sterol and So I use this fact which is well documented in this paper, which is ancient in the scheme of things Look what happened with volunteers in This diet which was manipulated by the researchers oysters clams Crab and muscle diets low in cholesterol and high in Omega-3 fatty acids lowered Vdl triglycerides Vdl triglycerides LDL and total cholesterol Squid and shrimp diets did not change blood lipids The ratio of LDL to HDL cholesterol was decreased on the oyster and muscle diets oyster muscle and squid diets increased HDL to cholesterol and Cholesterol absorption was decreased on the oyster clam and muscle diets Now you know why shellfish is my preferred animal protein source for apo E4 But we've found in our research and looking at other people's research that certain dietary supplements which are cheap They're readily obtainable at Costco at Trader Joe's online are Incredibly important in this battle This is a paper published in 2015 looking at grape seed extract It ameliorates fructose induced hyper triglyceride emion rats Via increased fecal bi acid and cholesterol excretion and inhibition of hepatic lipogenesis You want to get cholesterol out of you as fast as possible and you don't want to recycle cholesterol in the Enteropathic circulation so great seed extract which is cheap Again, Costco has a very good brand true nature have no relationship We have our patients take two a day How about grape seed extract and NAD insert one? This is a paper published just this year in April dietary proanthocyanins Boost hepatic NAD metabolism and Cert one expression and activity in a dose dependent matter and healthy rats Now this is in the liver But I can't imagine that the same thing is not happening in the brain So here's another exactly what we want to do and I'm not gonna Dale's gonna talk about this But cert one expression is critical to understanding the Many faceted effects of the apo E for gene Now how about turmeric readily available if you're buying turmeric I urge you to look for the word bioparin on the carton Bioparin is a derivative of black pepper. It's the easiest way to increase bioavailability of curcumin It's readily available. Just look for the words There's other great forms of absorbable curcumin that I won't go into today but the conclusion of this paper is that activation of cert one by curcumin blocks the neurotoxicity of amyloid beta in rat cortical neurons Conclusion from the paper taken together our results suggest that activation of cert one is involved in the neuro protective action of curcumin We found the pretreatment of curcumin prevented the culture of cultured cortical neurons from Amyloid beta-induced cell toxicity in addition curcumin improved mitochondrial membrane potential exactly what you want to do decreased reactive oxygen species generation and Inhibited apoptotic cell death in the amyloid beta treated neurons Pretty nice stuff to have circulating around in your brain I would say Now I know this is an ancestral symposium Unfortunately the paleo diet with its high animal fat and protein components Produces the exact opposite effect to what needs to happen in these people a Fact that we see repeated Over and over in our previously naive ApoE4s who come to my office now. I'm going to show you a patient and I apologize It's so small that I don't know how we're going to see it, but this is a young man in his 40s He carries the apoE4 for He inherited it from his mother and father Who I also treat his just as an aside his father came to me 12 years ago after being diagnosed with 4-4 an incredible executive real estate tycoon he's now in his mid-60s and He has not had any Changes in his mental status over the 12 years that I've known him But this is his son and his son is a crazy cross-fitter paleo Cheese loving give me triple cream breeze slathered on my grass-fed burger, and then I'm going to go to CrossFit So this Little line is what I want you to look at. That's sorry That yellow line. This is small down cell DLs is measured on cingula x and It's hard to see but he spends most of his time in the 40s and 50s I want him well below 30. That's when I start calming down and saying okay now we're there After this test I said, you know, give me a break here, you know, you don't understand What you're dealing with this is killing you I guarantee it. I said just throw me a bone Give up cheese for two weeks before the test and let's do your test. He said Two weeks. I said, yeah, just give up cheese two weeks. He said, okay, so he comes back Son of a gun. He's in green Now he said this is great news. I said, oh, I'm so glad you feel this way. You know, that's great news He says yeah, I can cheat the other you know two and a half months and stop cheese for two weeks and you'll never know and so he did and Here he is recently and he's still negative now. He actually believes that this is okay because he but For you crossfitters out there See this bright red thing up here Those are that's cardiac tropon and I it's a hundred times more sensitive than the tests We use in the emergency room look for looking for heart attacks he had done crossfit the nice night before and That is a tiny heart attack that he induced with his crossfit and The last thing APOE fours ought to be doing is crossfit. I apologize So he's a wonderful example. I just had to throw in at the last minute Using this protocol we have successfully minimized the deleterious effects of this ancestral gene and thousands of patients followed for up to 15 years With many APOE four fours successfully aging into their mid to late 80s our current oldest one 87 a couple months ago and Numerous APOE three fours now entering their 90s Now this may be the most important thing. I can tell you Many patients arrive later in life to our center and are found to carry the APOE four genotype Several have arrived thriving in their 80s with no cognitive impairment Interestingly enough and a dietary questionnaire of their habits throughout their life Most of these naive in other words, they didn't know they had the gene Scepto and octogenarians have a lifetime history of eating greens and a Dislike for animal products, but not a fondness for grains It's been a very very consistent pattern in my naive APOE fours who are thriving when I meet them so Eat like a Nigerian who lives in Greece or Italy Thanks very much Questions. Hello. Hey, I'm wondering if you've had a chance to look at Separating out the effects of dairy products from other animal fats I ask for two reasons one is that dairy can be very insulinogenic And the other is that it tends to be a lot lower in mono and saturated fats than say beef or pork Which are about half mono and saturated Good question. We actually have all of our patients only used grass-fed cheeses Cheeses from grass-fed cows and they're only allowed cheeses from KCNA to producing cows not KCNA one producing cows They don't get really any other dairy products except fermented dairy products, but yes What we have done is in most of these people the first thing we have done is taking away their cheese We've allowed them to have their grass-fed beef and limited amounts We've allowed them to have their grass-fed lamb and limited amounts The cheese is the factor that always kind of pops up on these folks. I'm sorry, you know Because we fours love cheese So I hope that answers your question I'm just wondering if you've been able to separate like done some trials where there or have seen some trials where there is There is high animal fat, but there isn't high dairy Yes, we these are these folks and When the dairy comes out then they come down But we we minimize the animal protein and our folks to about four ounces a day Maximum and we prefer to get their protein from fish because of the omega-3 fats And the other answer your question all of my patients the three fours and four fours run very low insulin levels And incredibly low apoE sorry incredibly low hemoglobin. Anyone sees Back someone in the audience has a yeah, you four less than four point two This young lady is less than four point two She's a four four or she said it I didn't yeah, so she's doing great. Yes, sir Yeah, so they have they actually are great sources of omega-3 fats But they're also a source of animal protein and I won't get into that today, but there's now two very large studies who that have recently been Published that show that animal protein is just as obesogenic as sugar something that I've been saying for the last 10 years and And They'll be in my next book the work that's been done at St. Louis University with calorie restricted society members Show that they don't reduce their insulin like growth factor one until they take animal protein out of their diet and then they approach the insulin like growth factor one levels of vegans and Insulin like growth factor one is probably the best marker. We have for accelerated aging in other words low is good high is bad and so I Am a Veg aquarium I eat mostly vegetables with a bunch of shellfish But I've through the years the more I can take animal protein away from Humans particularly the apoE4 is the better off we are Because we think that the apoE3 gene came about to allow humans to handle meat proteins instead of the Vegetable diet of the Great Apes They're actually very high in omega-3 fats In terms of protein much lower because which one much lower muscles clams grab shrimp are much lower in protein content Because they have far higher water content per ounce Yeah, ooh don't come near you non-fat yogurt. It's pure sugar It's pure protein Don't come near it Hi Have you looked at all at? Coconut oil coconut milk in April 4. Yeah So here's the deal This really really really really raises your small dense LDL's I see it over and over and over again Medium chain triglycerides on the other hand do not seem to have the same effect And I won't go into that because it's in my next book. We don't have time but it's because Medium chain triglycerides are a medium chain saturated fat and their handle completely differently than the rest of the saturated fats and coconut oil But yes, we we actually when we have people come in for testing We ban coconut oil for 48 hours before the test just to see what their actual baseline is So I don't recommend coconut oil as a staple for the apple e-Force And that coconut milk as well coconut milk is okay. It has far less saturated fat in it But you're better off with hemp milk as a as a milk hemp Yeah, hey you Colorado's no hemp. Come on He chew it and you eat it and you're smoking. Oh, that's its cousin. That's right Yes, Stephen. What lab do you use if we work in a regular medical clinic? Is this a lab that lab core quest or is this a Yeah, actually a quest can do now apple e-Force Quest singulax True health There's a prism lab now in Austin can all run these small dense LDL's There's now two labs that can run Oxidized LDL and we for the last year have been running Oxidized LDL's on all of our patients one of the labs is vibrant. The other lab is true health It's it's a very interesting gene test. The gene test so quest will do it Lab core can do it. Okay true health can do it. It's 23 and me if they're you know if money's an object just say I'm do 23 and mean carry it into you It'll be on there. Thank you. Yeah, I think With this question came up at lunch I think every human being ought to know their status because there's something they can do about it. This is not fate 23 means what 99 bucks 120 bucks 200 now they went up But medic Medicare pay Medicare pays for the Apple e-Test. It's Medicare covered And Medicare also covers the mth fr mutation test Does lipoprotein little a fit into this at all great question? You wouldn't believe the number of people who carry the Apple e-4 who also carry LP little a production. I actually think that these two are tied hand-in-hand and I believe that As you know the LP little a was sometimes called the northern European gene the Irish gene the Scottish gene the English gene because it predominates in northern climates and Linus Pauling was convinced this was because as we left the Mediterranean We ran out of vitamin C containing foods in our diet and vitamin C As you know is essential to repair the brakes and collagen that occur in blood vessels And if you don't have a vitamin C you hemorrhage internally Scurvy is half the people in ancient voyages died by hemorrhaging internally because they couldn't repair their cracks and blood vessels So Linus Pauling's theory, which has actually been proven now by Matthias Wrath is that LP little a acted as a Dutch boy who put his finger in the dyke and patched these cracks and if you carry this gene that made LP little a you would patch the cracks long enough To have babies before and you wouldn't bleed to death now again from a genetic standpoint Your genes could care less about you as long as you make another copy of you You're now disposable and so what appears to be a very bad gene is Actually an incredibly good gene to produce babies in the northern hemisphere And I have the sneaking suspicion that the apo E4 predominates in Certain cultures I mean 30% of people carry it because it probably is involved in that Spackling complex and may explain why we get the same lesions in the brain. That's how I got interested in it Thank you great question So the lab test I've been having a hard time getting outside of specialty labs is the omega-3 index. Who does that? Oh gosh True health does it True health out of Richmond, Virginia. They used to be called health diagnostics, but they're now called true health prism sometimes called PHDX like doctor and Lab core will do it We we get it down there Oregon's different. Yeah, so thank you One minute last he's got his hand up. Can you know it's a it's a different it's a different protein But yeah, but you can't blame your 6% body fat on that That's a joke Okay, well, thank you so much for your attention pleasure to be here