 So this was a logo from my website practical evolutionary health.com which I started, oh, I guess 10 years ago or so so it turns out that all the Lifestyle and nutritional elements that affect general health affect the immune system. No surprise and unfortunately Well wrong one. Oh, this is tough on 12 percent of American adults or metabolically Healthy in the u.s. And we'll talk about that later affecting our immune system and our ability to deal with this virus and Includes a lot of things going around clockwise Iatrogenic issues proton pump inhibitors much over prescribed NSAID steroids biologic Monoclonal antibodies all these things interfere not just with general health both with a properly functioning immune system We have the food industry that we're all well aware of Social isolation loneliness depression. There's evidence that supports that adversely affecting the immune system Disruption of circadian rhythm Excessive indoor activity artificial light cigarettes alcohol only these things we understand Suck our opinion is probably underappreciated as being Very important issue Tommy Wood a friend of mine gave an excellent talk at Physicians for Ancestral Health on the fact that Muscle mass is the single best predictor of health span and lifespan Sedentary behavior speaks for itself sleep deprivation stress pollution We're all drinking plastic and eating plastic every day whether we like it or not A lot of people don't understand that heavy metals in our seafood and in our oceans come primarily from coal burning power plants endocrine disruptors Plasticizers all these things adversely affect our immune system What helps our immune system are all the things that we talk about in ancestral health stress management sunlight laughter love Community sense of purpose clean air clean water nutrition sleep exercise social connection all those are important I'm going to talk about data That talks about all of that No conflicts of interest I started out in economics Was interested in health care policy health care management was a hospital administrator for a few years before I decided to go to medical school I trained in three specialties got triple boarded My early research interests were in cardiovascular physiology I had a lot of pain management training in anesthesia because of my previous training in critical care I didn't need to do electives practice operating room anesthesia for Over 30 years and in the clinic in the last five years transitioned out of the operating room into the pain clinic I was a vegan for one year with my son I came out in the morning He was eating bacon and eggs and a salad and I said what happened to vegan. He said I'm paleo now I said paleo what the hell is that? He told me I read his books. I went from arguing with him about it to following his lead So thank you to my son. I Polina say this is here many of you know her She invited me to my first physicians for an ancestral health meeting where I gave my first talk there and I'm forever indebted to her for that okay To decrease the risk of long COVID prevent COVID or at least decrease your risk of severe acute COVID because That's a prognostic indicator for long COVID. You can have mild or asymptomatic COVID and still get long COVID, but the probability increases with the severity of the disease So how do you do this lifestyle ancestral most of the talk? Vaccination there are a lot of anti-vaxxers in this space and I'm sorry, but One statement about that five months into Vaccinating in this country before 50% of people were vaccinated Vaccinated across the country in every ICU 90% of the critical ill patients with PCR positive or COVID-like illness were unvaccinated 10% were vaccinated and 95s work my niece was a critical care nurse and nursing director They have to be properly fitted to test that they squirt Two different aerosols into your face and if you can taste them or smell them It's not a proper fit HEPA filters are highlighted So by happenstance Virtuously in South Korea two years before the pandemic hit There was a movement in the school system to have HEPA filters put in all of the HVAC systems because of air pollution in the cities So when the pandemic hit they had HEPA filters in every HVAC system in a primary and secondary school system and they worked There's data to show that it worked. I gave two talks last year On a nutritional immunology and there were four hours So we're going to go at warp speed faster than the speed of light through a wormhole of slides today so I close all of my blogs since the pandemic with these statements regarding ancestral practices And these all have documented data to support Their efficacy in supporting the immune system and I tried to come up with some mnemonic So we got the essence sunshine stress sleep social connection skeletal and smooth muscle Smell the flowers and trees forest bathing sauna heat shock proteins saunas as good as cold exposure Seafood omega-3s producing pro-resolving mediators Supplements chrismaster. John has done a great job. The Institute of Functional Medicine has done a great job and my Humble website discusses some of that Short-circuit fatty acids support your microbiome soluble fiber. I know there's a lot of carnivores here, but there is data to support The interaction between your your gut microbiome any immune system toxin avoidance the 1t We're surrounded by toxins including emr screen time noise skin food water air I had My wife's urine and my urine tested several years ago. We live in an urban area. We're on well water and We found metabolites of jet fuel and all sorts of things. We're we're not near any industrial area studies done In papua new guinea 5000 foot elevation No industry in the area breast milk having over a hundred environmental toxins in those women It's everywhere These are some excellent sources on the interaction between nutrition and the immune system And doctor akiko iwasaka if you want to follow somebody on twitter That will keep you abreast of the latest information on immunology and this virus She's the person to follow Okay, so Let's get into it So what makes this virus so bad? Well, there's a lot of things that make this so bad it undermines the immune system The innate immune system has evolved In a way that gets rid of most viruses successfully But in about five percent of patients it doesn't work well We've all heard about cytokine storms over production of diverse signaling molecules In most cases inflammation resolves and we don't get a cytokine storm But when it happens it can cause acute respiratory distress syndrome Also referred to as non-cardiogenic pulmonary edema which can cause lasting lung damage and damage to other tissues It can lead to build up a fry brin so This causes blood clots a deep venous thrombosis pulmonary emboli blood clots in the brain Fluid leakage into the lungs triggering respiratory failure Usually The immune system doesn't overreact But in severe covid cases the damage is done because of the inflammatory response that continues after the virus is cleared Bradykine and storms is not mentioned much in the literature but it's a major problem and contributes to many of the pathophysiologic Observations in severe covid patients including cardiac arrhythmia of sudden cardiac death So, uh, there are several things that make this virus very different from previous viruses asymptomatic contagious state There is a protein that can block interferon production and the effects of interferon and this is a key Part of its pathogenicity If your innate immune system can't produce interferon and if the interferon is not recognized and and working The innate immune system does not work so seven days into Symptomatic infection is a key time. Are you going to make it or not? And the hyper inflammatory state usually starts seven days into viral lungless leading to multi organ involvement in nets Neutrophil extracellular Traps this can occur with other viruses, but it's a predominant factor and critically ill patients with covid And uh, the lungs fill up with hyaluronic acid, which creates a gel Hyaluronic acid can absorb a thousand times its weight in water And can you imagine a gel Filling your lungs trying to pass oxygen in one direction and carbon dioxide in another So as of january 1 2021 6700 times as many sores covid-2 patients as sores covid-1 worldwide so big difference Stroke and young people myocardial infarctions myocarditis so Brief note on myocarditis In the past myocarditis Associated with viral illness Resulted in about 12 of people needing heart transplants There have been no vaccinated individuals That developed myocarditis that have needed a heart transplant. There's a big difference between myocarditis That results as a complication of the vaccine versus myocarditis that results as a result of viral illness pulmonary emboli dvt pediatric inflammatory response loss of smell and taste recently published not published Not peer reviewed but preprint demonstrates that This is a risk factor for a subsequent cognitive impairment with long covid So loss of smell and taste that makes sense olfactory system Connected to the central nervous system So there's wide estimates that vary 30 percent of outpatients 60 percent of inpatients develop long covid symptoms And we'll talk about what those are And that was before the vaccine Okay, we're going to run through brady kind of storm. Sorry Of course, I've already mentioned most of that stuff. I wanted to introduce you to that term okay, so at the furan on the left SARS-CoV-2 on the right virus X so the red X Interferon is not being produced and it's not doing its business at interferon receptors That's how people get very sick. It disrupts the innate and subsequently the adaptive immune system And when it goes very bad, there's a cytokine storm Here's an air sac In the lungs Okay, obesity and leptin resistance. This is a brilliant 30 page review article One of the authors is Pedro Bastos. Is that right? Is he up there? Yeah, he'll be talking remotely from portugal He and I communicate on a regular basis almost daily This is a hallmark study we've already stated that Interferon production early on is inhibited by the virus and that the interferon mechanisms are interrupted by the virus So if you're obese with leptin resistance and insulin resistance, you've got a double hit Your interferon isn't going to work. That's why there's such a high mortality rate in that population So this is just a graphic this description of how this works So type one at the furan early robust response shows The t-cell response the viral load going up and down interferon going up and down t-cell response Happy patient on the right the laid response The viral load is dramatically higher It doesn't drop down the t-cell response also is is very low End delayed and when interferon starts to come up It's too late. And then interferon which is supposed to protect you actually starts harming you And some more details about how this works Metaflamation is a term these authors used to describe chronic inflammation associated with leptin and insulin resistance and obesity so Too late a response too weaker response of the innate immune system associated with leptin and insulin resistance Obese people have a chronically activated immune system. So there's chronic low-grade inflammation throughout the body And the immune cell insulin resistance immune cells have insulin receptors And they become insulin resistant and therefore they cannot behave optimally And so there's dysregulation of the entire immune system both the adaptive and the innate So there's an energy or a failure to respond Already talked about these and by the way, I've asked that a pdf file of these slides be made available because i'm rushing through to try and cover a lot of topics So um, this is a graphic uh display I co-opted this from an article, but I added a whole bunch of stuff in red And it shows the multiple interacting feedforward positive Feedback systems that occur as a reason and we talked about low-income lack of fresh nutritious food and and um The food industry fast food energy dense but micronutrient poor Hectic lifestyle which leads to more fast food pollution cigarette smoke sleep disturbance all compromising immune function And I added gut dysbiosis I don't have a lot of slides on this but Dysbiosis is a major issue in terms of the appropriate immune response Both in terms of lacking a good innate immune response and in causing an excessive Response late in the infection Iotrogenesis again many drugs proton pump inhibitors more than double the risk of severe covid This was a great article that came out early in the pandemic in nutrients 2020 so One of the points of this slide is that there were so many nutrient Factors vitamin e c beta carotene selenium zinc omega 3 fatty acids Sugar intake being negative vitamin d important in several pathways iron of course required by immune cells Carotenoids vitamin a proteins you need protein obviously to make antibodies and to mount an immune response Eating nose to tail Is very important because if we just eat muscle meat, you know that we're not getting a good balance of of proteins I mentioned in there the microbiota short chain fatty acids, which are the major energy source for the cells that line the gut epithelium And short chain fatty acids are also signaling molecules very important for Properly functioning immune system both preventing an overreaction or an underreaction and Tommy wood was a co-author on a study that showed that a ketogenic diet producing beta hydroxybutyrate probably supplies the gut epithelium with adequate energy And so that there's no danger if you don't eat A lot of fiber, but That's theoretical, but there's good evidence to support that but I do think that eating some fiber To support your microbiome Is still important So even though i'm not a complete carnivore Um on that end of the spectrum Another review article adjust to show you the complexity of nutrient interactions with the immune system I can't I could spend an hour talking about this slide, but I won't But you can see at multiple steps in the innate immune system and the adaptive immune system That there are so many inputs and and chris master john talks about this a lot Had tipped to chris master john um Specialized pro-resolving mediators which come from epa and dha are absolutely essential Not just to resolving inflammation, but in supporting the immune system and we'll see a slide about that later Okay, so this comes from a review article From n. Haynes data and you know food frequency questionnaires They're terrible, but they do provide some data Okay, so there was an n. Haynes study. We'll talk about it talking about all of these nutrients Um that play synergistic roles and I would add vitamin k2, but let's get ahead. So this is the study so Estimated average requirement. That's a terrible bar. It's such a low bar It's it's the nutrient value estimated to meet the requirements of 50 percent of adults to avoid deficiency That's a pretty low bar. It's certainly not optimal, but let's look at what the study based on food frequency questionnaires, which are not great data, but These are the percentage of people that didn't even meet that low standard and they included sleep, which was interesting So two-thirds of people in this country are sleep deprived That that's supported by a lot of data So, um interesting thing copper because you know The best source of copper five minutes. Oh my god. We gotta move Okay, so ancestral diet meets all of these needs right So vitamin d deficiency associated with very severe covet Um probably a cause and effect relationship Uh vitamin d affects barrier function in the lung and in the gut And it it helps produce defensons catholocyte in which are a viral cycle and it modulates the immune system essential pro-resolving uh mediators EPA and dha important to resolve inflammation, but also important In producing An innate immune response So omega-3 fatty acids are the good guys the dark side is omega-6 In vegetable seed and grain oils So the importance of pro-resolving mediators Is this depicted here on the right side? You have inadequate Control on the left side you have balanced control of the immune system And in this slide you can see on the right side that with adequate omega-3 Versus inadequate omega-3 on the left side all the bad things that happen Pro-resolving meteors help clear cellular debris block cytokines inhibit leukocytosis and enhance the adaptive immune system melatonin in in not randomized controlled trials but in observational studies and in uncontrolled Trials melatonin decreases a mortality rate in ICU patients on ventilators and intubated And there's a lot of good data on that. We're going to flash through it But it's clinically significant. We're talking hazard ratio of 0.27 That's that's a dramatic 3 to 1 reduction in in Death More studies on melatonin. So when I travel I take 5 to 10 milligrams that night. I think it's a good idea This is from a study or a discussion of melatonin relative to ebola virus Effective sleep duration. Let's go back So Two studies volunteers got squirted with rhino virus in their nose Those who had poor sleep Were much more symptomatic for a longer period of time So immune response to vaccination is also affected by sleep Okay, pull off it a virologist pediatrician argues against treating Fever fever is an adaptive response. It enhances your immune system Sona does the same thing heat shock proteins And other mechanisms. So Don't treat a fever with drugs Let it run its course Unless you get a seizure from a fever, which is very unusual and usually Does not cause any severe damage Meditation has been studied relative to measurements of immune function and duration of illness during the Winter season when respiratory viruses are dominant Both exercise and mindfulness meditation training decreased a number of days lost from work Statistically and clinically significant this these bar graphs show that So mindfulness meditation only 12 of american adults are metabolically healthy Based upon not requiring drugs to achieve Blood glucose triglyceride HDL blood pressure and a waste of conference Or normal measurements insulin resistance and by the way also leptin resistance is related to all of these So we know that there have been studies that show dramatic results to a paleolithic type diet within a few weeks Type 2 diabetes Compared to the american diabetes association recommendations better glucose control and lipid profiles Most of the people in a study that were insulin resistant improved their insulin sensitivity on paleo 14 days did it pretty amazing Multiple studies done This one in a metabolic unit at uc usf dr. Farsetto Again tremendous changes within a week or two This was a six month study comparing Mediterranean diet and paleo wins out A great review article again Pedro Bastos is a co-author So there's modulation of immunity studied in many publications insulin resistance obesity metabolic syndrome increased risk Ancestral diets likely decrease Several articles published in the integrative medicine literature This is from the institute of functional medicine talks about supplements if you're interested Um They talk about the same things that I previously mentioned sleep stress sugar alcohol vitamin cd Fat soluble vitamins zinc very important Curcumin possibly some benefit Coconut oil has antiviral properties properties Forest bathing improves the immune system Stress hormones decrease immune function increases within a few days of spending Three days and three nights in the forest Okay, um lots of different Estimates for the prevalence of long covet probably because of the variance changing and the way they define long covet These are factors that contribute to differences in the estimates So anybody who gets pneumonia or anybody who spends time in the icu is going to have long term Consequences so is is post covet? syndrome any different probably But there's an overlap between post icu and post ards syndromes and covet chronic fatigue syndrome myalgic encephalomyelitis Shares many features and they probably overlap with post covet lots of nutrient deficiencies found in these people Abnormal natural killer cells and immune dysregulation So this was a survey of of symptoms fatigue muscle weakness shortness of breath multiple systems involved with Long covet Number of responses from top to bottom So different theories autoimmune molecular mimicry and haptine model of autoimmunity A tissue alteration or binding of a drug or an environmental toxin or a virus resulting in autoimmunity persistent virus And reactivation of virus and I just read a paper published A few days ago that showed a immune profile of Viral reactivation with ebv predominantly And a antibody response to virus although no virus Of covet is detected. So the immune system is I got to stop Let me um see What i'm just going to mention the cell danger response theory. This is an amazing review article and and uh It explains a lot of what goes on with chronic illness and may explain most chronic illness This is a fantastic article that Talks about measuring multiple metabolic pathways over 600 metabolic pathways and identifying Six is it six and 13 and men and women that have chronic fatigue syndrome Um So there's a down regulation of mitochondrial production of ATP that is In theory removing Energy from the pathogen. So the virus doesn't have the energy to replicate presumably a um Protective mechanism, but I would encourage you to Um Read that article. Yeah, we're gonna have to go. I know i'm over time So a lot of auto antibodies identified in covet 19, but a most recently published article that I read yesterday couldn't put on the slides thank god Shows that the auto antibodies don't seem to have a tissue response and that's either persistent viral antigen With a non living virus Or reactivation of other viruses This is the immune signature that has been found in a recently published study. So autoimmunity less likely to be the culprit in long covet and um cognitive complaints CSF shows an abnormal inflammatory profile with Um proteins in the csf in symptomatic patients Um, so I've run out of time. There's a lot more to talk about. I'm just going to say that um In terms of cardiovascular and pulmonary physiology, there's a discordance Between the findings on standard and research testing For cardiac function and pulmonary function and the symptoms that patients complain of at at three months post covet the there is a strong correlation between the symptoms and the studies with mri of the lung and the heart and with, um exercise stress testing and other modalities, but at six months, there's a divergence Even though there are some persistent abnormalities on average. They're much lower and the the response is that There there are symptoms that don't correlate with the abnormalities on testing So this gives evidence to the fact that it is likely a mitochondrial dysfunction Which lends credence to the theory that I presented earlier We don't have any more time. Sorry. Um, I thought I'd be able to rush through and cover um A lot more topics, but take home message would be that um With long covet There's an immune response. There's evidence of active inflammation As if someone is responding to a viral infection There are there is evidence of reactivation of latent viruses such as epstein bar But there are also there's ongoing antibodies being produced against the SARS-CoV-2 virus even though there's an absence of any active infection and um, this may all be explained by the theory of mitochondrial um Down regulation and immune overreaction And there's probably a combination of of these factors amongst different patients Um, I'm gonna have to end it here because I'll be running right over