Paul Saladino· MD
humans we have been eating lots and lots of meat in fact the hypothesis the premise that I advanced in the book is that it was eating meat that made us human so to suggest that there is an evolutionary mismatch between eating meat and a belief or doesn't really make sense evolutionarily speaking in terms of our history because we've always all had a belief or it would have been not advantageous for humans to have problems with a belief or eating saturated fat from animals for the entirety of our existence if this were a problem because we all have a point for ancestrally what we did most of us now have a belief 3 or some of us have a pre 2 but the transfer of cholesterol between astrocytes and neurons in the brain is really important to know about why because the brain can't really transport cholesterol across the blood-brain barrier has to make its own cholesterol and then move it between astrocytes and neurons so what we're seeing in a lot of people with Alzheimer's is that insulin resistance in the brain makes the something about that transfer between the astrocyte and the neuron more difficult but in people who are insulin resistant apoe4 works even worse but does everybody with an e belief or polymorphism get Alzheimer's no and are there populations in the world who are not insulin resistant who don't demonstrate an increased risk of cognitive decline with a belief or there are and this is what is so fascinating so there are two populations that have been studied in detail that I want to tell you guys about they are the Bolivian semane and the Nigerian Yoruba and in both of these populations where there's a high proportion of apoe4 this genotype this polymorphism is protective against cognitive decline so the studies I want to highlight for you guys are these inflammatory gene variants in the sim main and indigenous bolivian population with a high infectious load and they said that the carriers of a Bowie for had lower levels of CRP and il-6 so they had lower inflammation and there's a separate study in the semane which shows that they have improved and maintained cognition there's another one a belief for is associated with improved cognitive function in Amazonian forager horticulturists with a high parasite burden these are the these Bolivians see Monet as well and i will read this older adult before carriers with a high parasite burden burden either maintained or showed slight improvements in cognitive performance whereas Nani 44 carriers with a high parasite burden to a reduced cognitive performance being an e4 carrier is the strongest risk factor to date of Alzheimer's and cognitive decline in industrial populations it is associated with greater cognitive performance in individuals facing a high parasite and pathogen load suggesting advantages to the e4 allele under certain environmental conditions the current mismatch between post-industrial hygienic lifestyles and active parasite rich environs may be a critical for understanding genetic risk for cognitive aging so what is going on here the apoe4 story is much more complicated than we have been led to believe we probably had parasite and pathogen exposure for the majority of our evolution and a belief war was probably very beneficial and protective against cognitive decline but what has happened now we have a new problem and this problem is insulin resistance and what we know is that in settings of insulin resistance 84 appears worse but if we don't have insulin resistance a belief you're is probably not a problem at all and not everyone with a belief or gets Alzheimer's or dementia but how much of the population has insulin resistance a huge amount of the population has insulin resistance if you look online you will see estimates 35 to 50 percent but there's an incredible study prevalence of optimal metabolic health in American adults National Health and Nutrition Examination Survey 2009 to 2016 they looked at very interesting metrics of metabolic health they defined that his optimal level of waist circumference less than 102 or 88 centimeters respectively from men and women fasting glucose less than 100 milligrams per deciliter hemoglobin a1c less than five point seven blood pressure less than 120 over 80 triglycerides less than 150 an HDL greater than forty or fifty milligrams per deciliter respectively for men and women and not taking any related medication and how many of the population met these guidelines less than twelve point two percent in fact it was 12.2% only met the guidelines so eighty seven point eight percent of the population in the US can be considered to be metabolically unhealthy this is crazy if everyone in the US looks like they have insulin resistance everyone in quotes like the majority of people in the US have insulin resistance of course apoe4 looks bad but in populations that are not insulin resistant apoe4 can even confer a benefit a Bowie for is only an issue if we are insulin resistant associations between saturated fat and a belief or our epidemiology there's no mechanistic data here guys and saturated fat is not bad for humans in and of itself anyone that says saturated fat is bad is looking at epidemiology so why is this misleading the people who are eating in the most saturated fat are people who are insulin resistant because what do they eat the saturated fat with this is why epidemiology is so so misleading and we can't rely on this can we see other things which make this seem like there's a discordant we absolutely can here's a case study apoe4 the door to insulin resistant dyslipidemia and brain fog a case study this is so interesting so this was a ten-week clinically prescribed ketogenic diet with a 68 year old male heterozygous for 84 had a dual diagnosis of mild Alzheimer's disease and type 2 diabetes so this is someone with insulin resistance apoe4 and cognitive impairment because he has mild Alzheimer's he got 10 weeks of a ketogenic diet which is gonna be high in saturated fat most ketogenic diets are and what happened cognitive improvements happened an insulin resistance got better so there is no problem eating saturated fat from animals or coconut or anything with a belief or in the setting of insulin sensitivity it's only because the entire population looks insulin resistant that we see