Podcasts about selye

Unlock the secret to maximizing your fitness potential and steering clear of the dreaded plateau with me, Rob Maxwell, your guide through the intricate landscape of periodization in exercise planning. Discover how this strategic approach can transform your training, whether you're an elite athlete or a fitness enthusiast. With a focus on the stress adaptation syndrome cycle, I'll illustrate why periodization isn't just a fancy term but a crucial tool for avoiding burnout and boosting performance. You'll gain insight into the classical linear method's structured intensity progression and the undulating approach's varied weekly intensities, learning which style might best suit your unique training demands.Ready to elevate your strength training game? The second part of our discussion zeroes in on the tangible benefits of methodically increasing weight loads. I'll share how a workout card is more than just a tracker—it's a roadmap to success that aligns with the Selye stress adaptation model. Whether you opt for a linear climb or prefer the diversity of a nonlinear routine, the emphasis remains on the power of a well-crafted plan. By the end of our conversation, you'll be well-equipped to either give periodization a whirl in your own regimen or fully appreciate the thoughtfully structured workouts your gym provides. And let's tip our hats to the local businesses that support our fitness journeys and the communities they enrich.

“The history of science, it turns out, is filled with stories of very smart people laughing at good ideas.”—Katalin Karikó Ground Truths podcasts are now available on Apple and Spotify!The list of obstacles that Kati Karikó faced to become a scientist, to make any meaningful discovery, to prevail over certain scientists and administrators who oppressed her, unable to obtain grants, her seminal paper rejected by all of the top-tier journals, demoted and dismissed, but ultimately to be awarded the 2023 Nobel Prize with Drew Weissman, is a story for the ages. We covered them in this conversation, which for me will be unforgettable, and hopefully for you an inspiration.Recorded 30 January 2023, unedited transcript belowEric Topol (00:06):Well, hello, this is Eric Topol with Ground Truths, and I am really thrilled to have with me Kati Kariko, who I think everyone knows won the Nobel Prize with the Drew Weissman in 2023 and she has written a sensational book, it's called Breaking Through. I love that title because it's a play on words, a breakthrough and breaking through, and we have a lot to talk about Kati, so welcome.Katalin Kariko (00:34):Thank you very much for inviting me.Eric Topol (00:36):Yes, well I'd like to start off, as you did in the book with your background in Hungary where of course you started with a tough background in a one room house without running water and you never had exposures to scientists and somehow or other you became interested in science and you attributed some of these things like your biology teacher, Mr. Tóth and the book Stress of Life [by Hans Selye] Could you tell us a little bit more what stimulated you in a career of science?Katalin Kariko (01:18):I have to say that every child is interested in understanding the nature around them and so I was surrounded with nature because we had big garden, we had animals around and it was an exciting thing. The children ask questions and if they try to find an answer and teachers or parents might give the answer, but definitely the school, even elementary school was very stimulating. Teachers, chemistry teacher, figure out how we can make crystals and I was so excited to have my own crystals and things like that and in high school the teachers were so engaging and not like they tried to put all of the information into your brain, but they encourage you to think yourself, so that's all contributed. I think that most of the child in the first, I don't know, six, seven years of their life that's how they can see their parents behaving, their friends, the school, classmates, and they shaped what kind of people they will be at the end and the rest of it is refining.Eric Topol (02:41):Right, right. Well one of the things I loved that you brought up in the book was how much you liked the TV show Columbo. That's one of my favorite TV shows of all time and one more thing, one more thing. Can you talk a little bit about Columbo? Because in some ways you were like the Peter Falk of mRNA in terms of one more thing.Katalin Kariko (03:09):Yes, so I realized that we as researchers, we are not called searchers, we researchers, so we are repeating things. Of course everybody knows who committed the crime in Columbo because this is how it starts and you don't have to figure out, but it seems always that things in a different direction you would lead but all the little clues and some of my colleagues said that they as a physician, they have this tunnel vision. So the patient comes and they can figure out probably from some clues that this is the disease and they get back the lab results and others. Then they realize that one or two things is not fitting, but they always so strongly believe their first instinct. What I taught them to focus on those which will not fit because that will lead to the real perpetrator in case of Columbo.(04:23):And so I like the simplicity. I know that what we are doing this research is very over complicated, but we can break down in very simple question, yes or no and then repeating things and many experiments. When I did one was the experiments really the question and the nine of them was like just controls always. I have to have a control for that, control for that and since I work most of the time with my own hands myself, so I had to make sure that I think through that what will be the experimental outcome and then think about that. Do I have a control for that? So that many times in my brain before I performed the experiment in my brain, I predicted that what will be the outcome, of course you never get the outcome what you expect, but at least you have the control that you can exclude a couple of things and so this is how I function usually in the end of the 20th century, 21st century people did not work like I did alone most of the time.Eric Topol (05:35):No, I see how you described it in the book was just so extraordinary and it really was in keeping with this relentless interrogation and that's what I want to get into is particularly the time when you came to the United States in 1985 and the labs that you worked in predominantly in Philadelphia through that period before leaving Penn to go on to BioNTech. So, you first kind of beached in at Temple University with a monster at least as you portray him in the book. I mean it was nice that he picked you up at the airport, you and your family. How do you say his name? Suhadolnik.Eric Topol (06:31):But not only was the lab kind of infested with cockroaches, but also after working there for a number of years, a few years, you then had gotten an offer to go to Johns Hopkins and when you informed him about that he threatened and did everything he could to ruin your career and get you deported. I mean this was just awful. How did you get through that?Katalin Kariko (06:58):As I mentioned later on, I went back and gave a lecture there and I have to say that I always put positivity in forefront, so I learned a lot from him, and he invited me to America. I was always very grateful, and he was kind, and we did very well, and we did a lot of publication. In one issue of biochemistry, we had three papers and two of them I was the first author, so I worked very hard and so he liked that, and he wanted me to stay there. I just learned that from this Selye book that this is what is given and then what I can do, I cannot change him. I cannot change the situation, how I can get out from it and that's what I focused on, so I am not bitter about him. I liked him and the same for other people. When I get an award, I usually thanks to all of these people who try to make my life miserable. They made me work harder.Eric Topol (08:05):Well, but you were very kind like you said when you went back to Temple many years later to give the lecture because what he did to you, I mean he was so vindictive about you potentially leaving his lab, which he demanded that he be called the boss and he was going to basically, he ruined the Johns Hopkins job. He called them and you were so nice and kind when you went back to give the lecture without saying a negative word about him, so I give you credit, when somebody goes low, you went high, which is nice.Katalin Kariko (08:40):It is important, which I learned from the Selye book, that you don't carry any grudge against anybody because it'll poison you and as Selye also said that when you are very frustrated and very upset, the quickest way you can think about how you can release the stress is revenge. He said, don't do that. It escalate. It hit you back. You have to think about how you can be grateful for the same person you were just ready to take some revenge and that's what you have to practice. Sometimes it is difficult to feel that, but I don't have any bad feeling against my chairman who put my stuff on the hallway.Eric Topol (09:24):Oh yeah, I was going to get to that. So then after a short stint at the Uniformed University of Health Science where you had to drive three hours from Philadelphia to go there and you would sleep on the floor. I mean, I have to say Kati, if I was driving three hours, all I'd be thinking about is how desperate situation I was put in by the prior PI you work with. Any rate, you work there and then finally you got a job with my friend Elliot Barnathan, a cardiologist at University of Pennsylvania. So here you are, you're very interested in mRNA and you hook up with Elliot who's interested in plasminogen activators, and you work in his lab and it's quite a story where one of the students in his lab, David Langer, ratted on you for being blunt about the experiments getting screwed up and then later you wind up working in his lab. Tell me a bit about the times with Elliot because he's a very gracious, I think he was very supportive of your efforts and you got him stimulated about the potential for mRNA, it seems like.Katalin Kariko (10:41):Yes, so I was desperate to be away from my family at Bethesda and try to get back and every day I sent out several applications. This was in 1989, so you had to send letters and then I called up usually the secretaries about what's going on and I called up also a secretary and she said that they were advertised because nobody was good enough. I said, can you ask him to look at again my application? Then half an hour later, Elliot called me back that come and bring your notebook. He wanted to know what kind of experiment I am doing, and he opened when I came a couple of days later and pulled up a northern blot and he said, you have done that? I said, yes, I did. He said, okay, you are hired and so that, because Elliot is just a couple of days younger than me, I convinced him that we should do kind of mRNA research and he agreed, and we did several experiments and he helped me to get all of these experiments ongoing and so it was a very exciting time and I listened. Elliot was there in many awards ceremony including the Nobel Prize. He was my guest because I was very grateful to him because I have to say that he tried to protect me and he get trouble for that because in higher up and when he was looking for tenure, somehow he get R01, several of them, but they did not put him tenure because he was standing up for me and he paid the price.Eric Topol (12:42):Do you think the reason in part that he went to Centocor, a biotech company who I worked with quite extensively was because he stood up for you?Katalin Kariko (12:54):He mentioned to the chairman that he's waiting for whether he will be tenured because he has a job offer with ReoPro what he was doing there in the lab and testing out and the chairman told him that, take that job.Eric Topol (13:11):Yeah. Well, that's interesting. I know Judy Swain very well, and she did everything she could to hurt your career. She demoted you, or actually she wanted you to leave, but you wound up taking a demotion and also Bill Kelley, who I know well, he was the Dean and CEO of the UPenn. Did he ever get any direct involvement with, because much later on he was advocating for your recognition, but during that time, he could have told Judy Swain to stop this, but did he ever get involved, do you know?Katalin Kariko (13:45):I was very low level of nobody, so he would not. It was interesting, we were hired on the same day in 1989. I was first, and I met him, Bill Kelley when the new faculty was hired, and I was so happy because my first project in Hungary was Lesch-Nyhan syndrome, and I know that he discovered the gene, and I was looking up to him very much always.Eric Topol (14:15):Well, you said in the book you were over the moon and I have to say, I worked with him. My first job was at University of Michigan, and I worked with him for six years before he left to go to Penn, and we've been friends all these years, but what happened with Judy Swain, as I read in the book, I got all it bristled. I really was upset to read about that. Anyway, somehow you stayed on, Elliot moved, by the way, during that time with Elliot, you were able to get mRNA to make urokinase plasminogen activator (uPA), and that was a step in the right direction. Before we leave, Elliot, if you had stayed there, if he had gotten tenure, do you think you would've ultimately together made the discovery that you did with Drew Weissman?Katalin Kariko (15:05):I couldn't be tenured because it is a clinical department and I had a PhD and nobody at the clinical department can be, but I could have been research associate professor if I can get a grant and in 1993, I already had submitted grant on circular RNA. When people in these days, they say that, oh, that's a novelty. Oh, in 1994, 1995, I had several grants on circular RNA I submitted for therapeutic purposes, and Elliot helped me with English and computer, everything what he could, but it is important that he was not an immunologist and I needed discovery. When I work with him, I did not realize the mRNA was inflammatory.Eric Topol (16:02):Right, right, exactly. We're going to get to that in a minute. Now, after Elliot left, then you needed someone else to support you, and you wound up with, as I mentioned earlier, David Langer, a neurosurgeon who you previously knew, and he also stood up for you, right?Katalin Kariko (16:18):Yes, yes. So at the beginning, every lab, when you have a medical student, they kind of know everything. One day he just told me that, Kati, I will want to learn everything you know, and I will know everything you know. I said, oh, by that time while you are learning, I learned so much more, you never catch me. That always I had to put him back, but kind of he liked how I worked, I concentrate, I didn't chitchat. Then he was just keep coming back when I was working, even with Elliot and he advanced from medical student to residency and so on, and then when he learned that I have no job because Elliot is leaving, then he went to a Eugene Flamm, the chairman of neurosurgery, and he convinced him that neurosurgery needs molecular biologics. That's what he was arguing and thanks to David and the chairman Eugene Flamm, then for 17 years I had a laboratory, and I had a financial support. Not much.Eric Topol (17:36):Yeah, I mean that was great, but again, you were not getting any real support from the university and then all of a sudden you show up one day and Sean has all your lab, everything that you worked on thrown in the hallway. I mean, that's just incredible story, right? At any rate, you then wound up because you were basically hawking mRNA as a path of science. It's going to be important. By the way, my favorite quote in the book, Kati. The history of science it turns out is filled with stories of very smart people laughing at good ideas. I just love that quote and it kind of exemplifies your career and your success, but you were steadfast and you ran in, of course, the famous story to Drew Weissman at the Xerox machine, and you were hawking trying to get anybody to believe it as you called it, led to the mRNA Believers Club, which only a handful of people in the world ever got there.(18:38):And here you have you take on something that obviously 1960 in your lifetime, early in your lifetime it was discovered, but everyone knew it was unstable, very difficult to work with, very challenging. Of course, you realized that could be beneficial, but you hooked up with Drew the immunologist that you mentioned, and I didn't know by the way, he had type one diabetes. I learned that from your book, and both of you worked so hard and it's just really incredible, but while you're at Penn, the famous or infamous Jesse Gelsinger case and his death occurred and he had the cytokine release syndrome, and you learned from that, right?Katalin Kariko (19:25):Yes. By that time, we also could see that the RNA could be inflammatory, but in his case, of course, because the virus was causing it or what certain condition caused that. I have to say that, people work at gene therapy at Penn and mostly of viral programs. When I mentioned I tried to make gene therapy with mRNA, of course everybody felt sorry for me. Poor Kati, hate RNA, it always degrade, but I have to say the degradation is coming mostly because the molecular biology laboratory, they use plasmid, and when they isolate plasmid, like the QIAGEN kit, they start with the RNAs. They add RNAs because you have to eliminate the bacterial RNA, and they contaminate the whole laboratory, the refrigerator door, the gel opera, everybody's RNAs and so that's what extra problem with working with RNA. So I could make RNA, and so it was working and kind of try to express that and I made a lot of RNA for people probably they still have in their freezer, never tested because I was a pusher.Eric Topol (20:52):Yeah, yeah. Well, what was fascinating of course is you had already learned in mice about this inflammation from putting mRNA in vivo, and then you made the remarkable discovery, which was the paper in Immunity that had been rejected by Nature and many other papers, even though you had been told if you could get a paper in Nature, maybe that could help your career, right. Back in 2021, the journal of Immunity, a very highly regarded self pressed journal, they asked me to comment on your discovery and I wrote, you may have seen it. Of course, several people wrote Tony Fauci and others. What I wrote was what began as a replacement for a uridine base to squash an inflammatory response in mice evolved into the basis for a broad therapeutic platform to fight both communicable and non-communicable diseases in people. So, this discovery that you made in that classic 2005 paper, which is the most important paper ever published in the journal Immunity, was the Toll-like receptor was mediating the inflammation.(22:05):And if you change the uridine to pseudouridine, you could essentially blunt or block the inflammation. This was a seminal discovery that opened up mRNA, but not just for Covid of course, but for so many pathogens and as we'll talk about when we wrap up about all these other things. So when you did this paper and Drew said when it's published, the phones are going to be ring off the hook and no one even acknowledged the paper, right? I mean no one realized how this was one of the most important discoveries in the history of biomedicine, right?Katalin Kariko (22:43):Yes. Especially knowing that Drew is not the person who is exaggerating things. Drew is very modest and would not say such things. I am more like daughter, maybe this happened, but he is not like that and I got the one invitation to go to the Rockefeller University for a meeting, and then I went to Japan from 2005 and it was 2006. Both of them that was invitation, and nothing happened in 2007, 2008 and 2009.Eric Topol (23:24):But those meetings that you went to, they were kind of obscure like microcosm groups. I mean they were relevant to your work, but they didn't realize this is a big deal. I mean, this is like a world changing type of finding because now you could deliver things in cells. Now of course, you worked on this for three decades and the people that think that you can do a flash in the pan science, but at the same time nanoparticles separately were being pursued. How important were the nanoparticles to make for the package for the ultimate success? When Covid hit in late 2019 and now you had been working at BioNTech, how would you rate the importance of the nanoparticles in the story?Katalin Kariko (24:23):For the vaccine it definitely is important because everybody ask the mRNA, if not immunogenic, where do you have the adjuvant? Where is the adjuvant? Then lipid nanoparticle contains an ionizable lipid, which was the adjuvant and why it is important that not the mRNA was inducing the response because the mRNA induced interferon, and if you have interferon, then follicular T-helper cells is not form, and then you get very low amount of antibodies, but if you do not induce interferon, but you induce IS6 and other cytokines is beneficial to have high level of antibodies, so that's what the ionizable lipid was causing and that's the adjuvant in the lipid nanoparticle. Yes, I always emphasize that it is very important and of course when we use the particle that was totalization, then it did not contain ionizable lipid.Eric Topol (25:24):Right? I think that's where there's a misconception because of the Nobel Prize recognition last year, a lot of people think, well, that's all tied only to the Covid vaccine. Actually no, your discovery was much bigger than that and it was applied for the Covid vaccine of course with the nanoparticle package, but yours is as we'll get to in a moment, much, much bigger. You left Penn, that was in 2013, and then you spent several years in Mainz, Germany working with the folks at BioNTech, and you really enjoyed that and they appreciated you then as opposed to what you dealt with at Penn where it was just that you kept hearing about the dollars per net square footage and all these ridiculous things and just extraordinary to go back there. Now I just want to mention about your own gene transfer, your daughter. Your daughter is a two-time gold medal Olympiad in rowing, which is incredible. So she didn't go down the path of science, but she also became a world leader in a field. Is that transmitted on a particular chromosome in the family?Katalin Kariko (26:54):I think that she just could see that you have to focus on something and then you give up many things and you focus and then achieve, and then you get the new goal, set up a new goal. I mean she get somewhat articulated at Penn, she get a master in science and later in UCLA, she get a MBA degree, but 10 years she was like, for me, it is a very boring thing, just rowing going backwards. Isn't that boring every day? She said, no, mom, it is fun. Every practice is different, I enjoy. The minute I don't enjoy, I will stop doing it.Eric Topol (27:36):Yeah. Well it's amazing story about Susan and of course the expansion of your family with a grandchild and everything else that you wrote about in the book. So now let's go to this story, the big story here, which is mRNA. Now you can get into cells, you can deliver just about anything. So now it can be used for genome editing, it can be used for all these different pathogens as vaccines and including not just pathogens but potentially obviously cancer, to rev up the immune system, neurodegenerative disease to prevent these processes and potentially even preventing cancer in a few years ahead. How do you see this platform evolving in the years ahead? You already have seen many vaccines getting approval or under intense study for pathogens, but that just seems like the beginning, right?Katalin Kariko (28:38):Yes, yes. When I came to Penn, the major advantage was going to lectures and when I went to the lectures, I always at the end of it think, mRNA would be good for it. So, I was collecting all of these different fields and then what happens is right now I can see the companies are making those RNA, which I thought that it will be useful and even many, many more things that they are applying and now it is up to those specialists to figure out they don't need me. They need experts on cardiology and other fields and allergies. There is also to tolerate allergies and there are so many fields scientists will be figuring out there what is useful for the mRNA, and they can just order now or create their own RNA and test it out.Eric Topol (29:38):It's actually pretty amazing because I don't know where we'd be right now if you had not been pushing this against all adversity. I mean just being suppressed and being told, put your stuff out in the hallway or being thrown out of the university and not being able to get any grants, which is amazing throughout all this time, not being able to get grants, it tells a big story and that's why the book is so sensational because it's obviously your autobiography, but it tells a story that is so important. It goes back to that memorable quote that I mentioned. You wrap up the book with your message of your life story, and I do want to read a bit of that and then get your reaction. My first message is this, we can do better. I believe we can improve how science has done at academic research institutions.(30:38):For one thing, we might create a clearer distinction between markers of prestige, titles, publication records, number of citations, grant funding, committee appointments, etiquette, dollars per net square footage, and those of quality science. Too often we conflate the two as if there's one in the same, but a person isn't a better scientist because she publishes more or first perhaps, she's holding back from publication because she wants to be absolutely certain of her data. Similarly, the number of citations might have little to do with the value of the paper and more to do with external events. When Drew and I published our landmark Immunity paper and indeed it was, it barely got any notice. It took a pandemic for the world to understand what we've done and why it mattered. I mean, that's profound, Kati, profound.Katalin Kariko (31:42):I have to tell you that what I could see as the science progress. Every scientist starts with understanding something to help the world but somehow they publish because they have something to say, but somehow, it's shifted. Now we want more money, more people would come, those people had to get publication because otherwise they cannot graduate. They need first to author a paper. They publish even when it is not finished or have nothing to say and then somehow the focus is promotion. You are advancing your position, and the tool is doing the experiments. If you see I was demoted, I was pushed out so if my goal would have been to see that I am advancing, then I would give up because that's what the problem is. So that focus is going away from the original thing that we want to understand the science because if you want to understand the science, you are even happy when you can see a publication doing half of that you have done already because you say, I wanted to understand, here's a paper they did, similar thing I did, but the people think, oh my god, my journal paper is out and my promotion is out because they discovered and they published before me, so that's the problem.Eric Topol (33:12):Well, I mean if I made a list of all the adversity that you faced from growing up in the Russian communist run Hungary to coming to the US not even knowing the language and also all the sacrifices you made along the way with your family and when you would go to Bethesda or when you moved to Mainz or I mean all along the whole time, no less what the university of Temple or Penn. I mean the list is very long and somehow you prevailed above all that, which is just so startling but another thing I want to just get into briefly, as you know, this has been a shocking counter movement to the vaccines and giving ridiculously the mRNA as a bad name. In the book, you kind of had a way to foreshadow this because back in the 1968 pandemic that you obviously experienced, here you talked about that.(34:30):You said we restricted our movement, limiting our contact with others. We scrubbed, we disinfected. I suppose the party encouraged this, but nobody complained about government overreach. This was a virus. It had no ideology, no political agenda. If we weren't careful, it would spread, then we would all suffer. These were just the facts. That's how viruses work. So how come we still don't know that? That was 1968 in Hungary and here we're go in the United States, and we have a huge movement, anti-vaccine, anti mRNA, Covid vaccines, and it's very worrisome because all the great science is threatened by this misinformation and disinformation. What are your thoughts about that?Katalin Kariko (35:27):Yes, I heard that viruses, they love democrats because everybody can do whatever they want, whereas in other countries give an order, everybody has to have vaccine and then that's different, but yes, I understand that the novelty the people were always against, even when X-ray was introduced, people thought that people will look through my clothes and seeing me naked because they take part of the truth and they don't say, maybe through the flesh is going through and I can see somebody's bone or something. Then they distort, and they create a fear and if you make fear, then you can control like Lord of the Flies, somebody you are afraid of and then you can control and you can be afraid of the virus or you can be afraid of the vaccine. Then that's what I don't understand exactly true said that when they investigated those who are spreading most of these news about against the vaccine is they are selling some kind of products benefiting just like a hundred years ago, those who were afraid that they can see through their clothes some they start to sell X-ray resistant underwear.(36:57):Of course people, they made money on the people's fear. I don't know that's how to fight it or I think that the honesty when the scientists would say that, listen, we don't know today how it spread. This is how we suggest, be afraid, wash everything. Oh no, we know that it is in the air so that okay, you don't have to wash your clothes when you go out and come back but don't go to crowded places. In politics it's not working because it is like wishy-washy. Yesterday you said something and today, because we learn, they have to understand this is a science process constantly correcting. In politician, I know everything, this is how to do, they want to reflect this confidence. That's what it is and that's why politics everywhere mixed up with this. Some leaders want to reflect this confidence and they do things which helps the virus to spread.Eric Topol (38:11):Right. Well, I'm glad to get your perspective because obviously when you work so hard throughout your career and then you see the backlash, that's unwarranted. It's always good to be circumspect of course, but to say that this was done in a flash in the pan and it's never really, it's gene therapy and it's changing your DNA, I mean it's a lot of crazy things that of course that you brought out in the book as well. Now before wrapping up, you wrote the book before you were awarded the Nobel Prize and this recognition, you and Drew of course became fantastic, so richly deserved, but many things occurred and I wanted to ask you. For example, you did your PhD and your postdoc at the University of Szeged in Hungary, and you went back there, and I think you were celebrated in your university, perhaps the first Nobel laureate. I don't know, I would imagine perhaps. The second, oh okay but also the last thing that was recognized in the book it was a much different thing. It was like the Time 100 recognition but now that you have had many of these unanticipated awards, what are your thoughts about that? I mean, it is wonderful to get recognized by the university that you trained and the people that you grew up with.(39:53):Has this changed your life or is it really very much the same as it was?Katalin Kariko (40:00):My life is very much the same as it was. I am living in the same house. We moved in 1989 and okay, last year I get a new car. Up until then, I never had, only just some beat-up, last year I purchased my first new car but that's luxury when you are 68 years old, you could afford. Everything was a surprise because 40 years I never get any award and the first award I get in 2021. I tried to articulate to more people, life as a scientist is similar to mine. They are immigrant, they are not recognized and I try to tell them just not to focus something like the university is not grateful. Who is the university? Just they are walls. What administrator would tap your shoulder. You have to know that what you are doing is important and if you get pushed around, you always have to do what Selye said, figure out what you can do. Always that, not what they should do. The agency should give me the money, the boss, the superior should help me. No, I cannot make other people to do. I have to figure out what I can do. I can write better and better and rewrite, generate more data for a submitted grant application and always, that's why all of these naysayers made me better because I'm not focused on revenge or anger, but always, how can I be better.Eric Topol (41:53):So that gets me to what you do next. I know you're an avid reader. I know you read so much about science and your field and broader of course I take it you still are doing that, but what's in the next chapter for you? I can't imagine you're ever going to rest.Katalin Kariko (42:16):No, no. I will be six feet under when I can rest, I realize now. It is just that you are on a different field, and you understand like nucleotides, how naturally you make RNA, what is the transporters, what is happening in the mitochondria, different things that iron sulfur clusters and then you start to investigate like three months I was just reading one topic. I didn't even know about it or how in my life I was reading so many things. I realized there are so many diseases, I understand what is the reason, people don't. When I was at Penn I went to different people, professors about my idea for certain diseases but I was nobody and nobody listened. Now, I'm somebody. I have to be very careful because I say a name of the disease people will line up here and say, don't talk to Eric. Go and do something, help us and so that's what I try to help. I think that I understand certain disease, which is so enigmatic and nobody has a clue and maybe I have a solution for that. That's what I try to do now.Eric Topol (43:38):Do you ever go to Penn? Do you ever go to work in there?Katalin Kariko (43:44):No, I don't. When you are forced to retire, and I knew that they would throw me out because it was 2012, right before Christmas I was told that get out because you didn't get the 2012. Last time I submitted an mRNA for stroke therapy. Still very valid and good idea but anyway, I knew that I will be pushed out, but I don't have grudge, even the chairman. How can I expect the neurosurgeon who is doing the operation he just can see that I did not get the funding and those people who make the decision that my proposal is not good, they are expert. He's not an expert. He just can see that this is what the expert said. I talk to him, I don't blame anything.Eric Topol (44:37):Good for you. I mean I think it's much easier to be vindictive and you have to have the philosophy that you have, which is not to hold any grudges after all that has basically been done to you by many people along the way and I think we've covered that. I know this is a very different interview perhaps than many others that you've had. I didn't bring up the teddy bear and I didn't bring up a lot of things that others have brought up because they've already been covered. I wanted to get into what you had to endure, what you had to do to persevere and how it has changed the life science and medicine forever and now, still today, the mRNA package will be improved. I mean we've already learned, for example, the change of the two proline substitution that Andrew Ward at my place, along with Jason McLellan and others to make it to better immune response. It can be improved with a 6-P proline substitution. We can beat nature just like you did with the uridine substitution and the nanoparticles will improve and this whole package has got an incredible future but it's thanks to you, if it induced massive inflammation, it never would've been possible.Katalin Kariko (46:02):Yes, I always said that hundreds and thousands of scientists, every time I thanks them, those people, even not with us, I was reading their papers and it all contributed to this development and learning. So, I am not thinking that I was many, many other people together, we did that.Eric Topol (46:30):Well, I am so indebted to you as everyone who understands sciences, and it's of course a bigger story than mRNA. It's what you endured and how you persevered and against all odds, I mean truly against all odds, so thank you. Did I miss anything that I should have asked you about?Katalin Kariko (46:51):No. I have to say the book came out and now I can see in different social media that how other scientists get inspired. There was one who said that she quit doing PhD and she read my book and she cried, she laughed, and she went back. She realized that there is more to it because so many is expecting to do some work and then there will be some rewards. The rewards is this is not a short distance. This is a marathon to be scientist and you have to see the goals and it will one day and you might not the one that cross first the finish line, but you are helping others. That's what is important and that's what I am glad that I work with this and write this book so that other scientists more can associate because they feel the same way, that they are not appreciated. Things are not going as expected and then they might be inspired not to give up and that's what is also an important message.Eric Topol (48:11):Well, that's why I love the book because it is so inspirational and it will make people cry. It will make people commit to science or appreciate it more than ever. I don't know if you saw it, but I put it as my 10 favorite books for 2023 and indeed, I could have been the most favorite in many respects. So I hope more people listening or watching the video will read the book because it has a lot. I'm so glad you wrote it, Kati, because if we only knew you from papers and Nobel Prize, you wouldn't know the true story. We wouldn't know really what your life has been like over these many decades. So, thank you for that as well and thank you from the life science, the medical community, and for everyone, for all that you've done to change the future and the current state of medicine.Katalin Kariko (49:10):Yeah, thank you very much asking and I might add to the book that the book is published in many different languages is coming Italian and French, German, Thai, Japanese, Chinese. So scientists all over the world can read their native language and maybe they will be inspired.Eric Topol (49:28):Oh, I have no question about that. It's a story that it should be a movie so that the people that won't read the book will hopefully watch the movie. Has there already been a plan for that?Katalin Kariko (49:40):There was, but I don't think that you know they have this strike during the summer, and I don't know where it ends.Eric Topol (49:52):I wouldn't be surprised if it gets done in the future and I hope they'll consult with you, not just read the book and it'll be interesting who they get to play you in the movie, but thank you so much, Kati. What a joy and I look forward to future visits with you. Get full access to Ground Truths at erictopol.substack.com/subscribe

Germ Theory vs. Bioterrain Theory. From Antoine Bechamp down to the present.  Learn which theory is based on best science and which one is driven by market demands and politics.  JD Rockefeller sends Abraham Flexner to all US med schools.  Censorship of pure scientists: Enderlein, Naessens, Carrel, Rife, Selye, etc.  Which theory enhances the immune system and which one suppresses it?  Define the immune system.  Ask your doctor to.  Why has Bioterrain Theory never been disproven?  Why has Germ Theory never been proven ?   Why does the US have 4% of the world's population and consume 40% of the world's meds?  And still has the worst health of any industrialized nation?Please share and subscribe.Other videos at www.thedoctorwithin.comFor more references on this topic, please visit: www.thedoctorwithin.comNewsletter ArchiveVideos

J'ai eu le plaisir de recevoir Delphine Fauvel et Marie Prevost de La Fabrique à Neurones au micro de Neurosapiens pour parler charge mentale, mémoire de travail, stress et capacité du cerveau !  Lien vers le livre de Gaël Allain : https://livre.fnac.com/a13259229/ALLAIN-G-Surchauffe-mentale Leur LinkedIn: https://fr.linkedin.com/company/la-fabrique-a-neurones Leur Facebook: https://fr-fr.facebook.com/LaFabriqueaNeurones/ Leur site internet : https://www.lafabriqueaneurones.com/ Production, animation, réalisation et illustration : Anaïs Roux Instagram : https://www.instagram.com/neurosapiens.podcast/ Pour toute question : neurosapiens.podcast@gmail.com Produit et distribué en association avec LACME Production. Musique  KEEP ON GOING Musique proposée par La Musique Libre Joakim Karud - Keep On Going : https://youtu.be/lOfg0jRqaA8 Joakim Karud : https://soundcloud.com/joakimkarud ONE NIGHT AWAY Musique de Patrick Patrikios Sources :  Fries, P. (2015). Rhythms for cognition: communication through coherence. Neuron, 88(1), 220-235. Miller, G. A. (1956). The magical number seven, plus or minus two: Some limits on our capacity for processing information. Psychological review, 63(2), 81. Selye, H. (1956). What is stress. Metabolism, 5(5), 525-530.  Cowan, N. (2010). The magical mystery four: How is working memory capacity limited, and why?. Current directions in psychological science, 19(1), 51-57. Tran., Y, Craig, A., Craig, R., Chai, R., & Nguyen, H. (2020). The influence of mental fatigue on brain activity: evidence from a systematic review with meta-analyses. Meta-Analytic Review of mental fatigue and brain activity. (57).

As we get into the holiday season, so much can trigger our stress responses, whether that is travel, family dynamics, fear of the new year, money, etc. This is a journey to bring you back into your body and remember that the greatest gift you can give yourself and your loved ones is your presence. This journey meditation can be done seated or walking. Come back to it anytime you need to release tension. Quote:From On Being Human pp. 79-82."Based on his own battle with cancer, Dr. Selye offered three ways to build a constructive life:1) turn feelings of resentment and anger, which lower resistance to stress, into respect and sympathy2) set goals for yourself; and3) live for the benefit of others, for in so doing, you yourself will benefit,email the podcast: gogentlypod@gmail.com for questions, bookings, etc.

Was ist Stress überhaupt? Was passiert in uns, wenn wir Stress erfahren? Passiert der uns einfach so, oder haben wir da selber etwas mit zu entscheiden? Stress ist hauptsächlich ein Produkt unserer Bewertung von eigentlich neutralen Sachverhalten und besonders unsere Prägung, Glaubenssätze und Erfahrungen spielen hier eine große Rolle. In dieser Folge besprechen wir, was Stress ist, wie wir Stress erfahren und auf welchen Ebenen wir Stress erfahren. WIr schauen zudem darauf, was wir für Möglichkeiten haben, Stress zu mindern. Wenn du Fragen oder Anregungen hast kannst du mir gerne einen Kommentar dalassen, oder eine Nachricht schreiben. Gerne kannst du mir Folgen, mich abonnieren, mir Daumen nach oben dalassen und mir tolle 5 Sterne Rezensionen geben :-) Wenn dir der Podcast gefällt, kannst du ihn natürlich gerne Freunden, Familie, Bekannten und Kollegen weiterempfehlen :-) In ca. zwei Wochen geht es mit dem Thema "Die Folgen von chronischem Stress" weiter. Solltest du für dich den Impuls gefasst haben, dass du endlich aus der Stressspirale aussteigen willst, aber HIlfe brauchst, kontaktiere mich sehr gerne für ein unverbindliches Orientierungsgespräch

Stresul este epidemia globală a timpului nostru. Și totuși, Hans Selye, cel care a formulat, în 1937, primul model teoretic și experimental al stresului, valabil și astăzi în liniile sale esențiale, considera că lipsa stresului înseamnă moarte, astfel că el a definit stresul ca sindrom general de adaptare. Din această perspectivă, stresul nu numai că este inevitabil, dar e indispensabil ca factor de succes adaptativ. Atunci când vorbim despre stres ca factor nociv ne referim la ceea ce Selye numea “‘disstress”, care apare în momentul când resursele de adaptare ale organismului sunt suprasolicitate. Stresul este o componenta inevitabilă a vieții. Daca înveți cum să-l gestionezi cu succes, îți poate îmbunătăți în mod semnificativ sănătatea mentală și fizică. Toți ne confruntăm cu situații de stres, însă folosim exemple diferite pentru a-l descrie. Tu poate definești stresul ca fiind traficul bară la bară, un termen strâns de execuție a unui proiect, o boala care îți provoacă griji sau o ceartă cu partenerul. Din punct de vedere psihologic, aceste exemple sunt interpretate ca factori de stres – adică diverse tipuri de evenimente și circumstanțe stresante. Iar a defini stresul într-un mod mai precis, acesta este un răspuns fizic automat în fața unor provocări sau a oricărei situații care îți impune adaptarea la o schimbare. Indiferent dacă factorul de stres specific cu care te confrunți este un accident de mașină, o ceartă puternică sau durerea provocată de artrită, fiecare amenințare potențială sau efectivă declanșează o cascadă de hormoni ai stresului care produc modificări fiziologice bine orchestrate. Cunoști cu siguranță aceste senzații. Inima îți bate mai repede. Mușchii se încordează. Respirația este accelerată, îți apar broboane de sudoare pe frunte sau îți transpiră mâinile. Însă modul și motivul pentru care aceste reacții au loc, precum și efectele declanșate atunci când aceste reacții se produc în mod repetat de-a lungul timpului - sunt întrebări la care cercetătorii încearcă de mulți ani să găsească răspunsuri. Folosirea regulată a tehnicilor de gestionare a stresului te poate ajuta să îți calmezi sistemul nervos și să restabilești echilibrul. Câteva metode de lucru pentru gestionarea situațiilor stresante sunt: · Dezvoltarea abilităților de comunicare; · Dezvoltarea relațiilor sociale; · Schimbarea perspectivei din care privim anumite situații; · Atunci când consideri că treci printr-o situație stresantă hobby-urile vă pot oferi momente de liniște, de relaxare. Sportul este de asemenea foarte important, pentru că ajută la îmbunătățirea stării de sănătate fizică și psihică. Este foarte important să găsești acel sport pe care îl poți face cu zâmbetul pe buze pentru ca efectul acestuia să fie maxim. Pe scurt dacă reușești să îmbini în mod corect viața personală cu cea profesională, atunci poți găsi acel echilibru care să te poată face să treci peste orice situație stresantă. Resursele de care ai nevoie sunt: · Somnul - trebuie să încerci să fie de calitate; · Viața personală - în care să încerci să găsești un partener pe care să te poți baza; · Sportul - te poate ajuta să te descarci de emoțiile negative; · Prietenii adevărați, cei care să îți fie aproape atunci când te afli într-o situație stresantă. · Psihologul. În concluzie, pentru a învăța cu adevărat să gestionezi situațiile stresante este bine să ai în vedere un plan extins la care să lucrezi alături de un specialist.

In this episode of The Thermo Diet Podcast, Jayton Miller sits down with independent health researcher and coach Jay Feldman. Jay has been in the metabolic health realm for years now and has a very comprehensive knowledge of various aspects of metabolic theory and the human body. In this episode, they go over misconceptions around adaptation and hormesis why our adaptation to something doesn't make it beneficial Adapting to something to survive or thrive why adaptations to stress are harmful and aren't responsible for the benefits from things like exercise Epigenetic factors the problems with being a "fat-burner" and low-carb diets Why we don’t want to use fatty acids as fuel Beta oxidation vs glycolysis Hormones associated with this type of energy utilization Instagram: - @_christopherwalker @researchcowboy  Jay's Website - https://jayfeldmanwellness.com/ Jay's Podcast - The Energy Balance Podcast https://umzu.com/  Full Transcript: Jayton Miller: Welcome back to Thermo Diet Podcast. I'm your host, Jayton Miller. And today I have on the podcast, Mr. Jay Feldman. I'm super excited for this episode. Some of the things that we talk about are the misconceptions and some of the misunderstandings around adaptation and hormesis, why our adaptation to something doesn't necessarily make it beneficial, adapting to something for survival versus thriving. Why adaptations to stress are harmful and aren't responsible for some of the benefits from things like exercise. We talk a little bit about the epigenetic factors. We talk a little bit about being a fat burner versus using the oxidative and glucose metabolism. So this is a very dense episode filled with information. I love talking to Jay, so I'm super excited for y'all to dive into this one. So let's get into it. Jayton Miller: How's it going today, guys? Welcome back to Thermo Diet Podcast. Today I have on the podcast, again, Mr. Jay Feldman. How are you doing today, Jay? Jay Feldman: I'm great, Jayton. How are you? Jayton Miller: Doing very well. For anybody who might not know who you are out there, you mind giving on a quick background story? Jay Feldman: Yeah. I, like many other people who end up trying to share a lot of health information and trying to help other people get better, I started with myself. Health became a real focus for me, starting basically with fitness where I was trying to improve my athletic performance, I want it to look good. And that took me down the dieting rabbit hole and nutrition rabbit hole. And I ended up making a lot of mistakes along the way, falling into low carb and a lot of caloric restriction trying to stay lean. After finding a lot of things that didn't work and ended up making me feel a lot worse, through that exploration and trying to figure out what was wrong, I ended up coming across what a lot of people call the bioenergetic view of health, and changed everything for me. Jay Feldman: And now I watch how much it changes the lives of other people, and I think it's a much better approach, of course, as we'll talk about today. Jayton Miller: Definitely. So for those who might not know the general perspective of the bioenergetic view, do you mind given your quick definition of that? Jay Feldman: Yeah. It's basically the view that our health is dependent on energy. Basically, the energy is the center of our health. And when I say energy, I'm not talking about some spiritual energy or anything like that, but rather energy on a physiological level, the actual energy that's produced in what everyone says is the powerhouse of ourselves, the mitochondria. A lot of times we'll talk about it in of ATP, but there's other... ATP is a good a barometer for energy, but energy can be held in all sorts of molecules and structural compounds. And so, it's looking at how, basically, all of our health, whether tissues or our ability to thrive, all depends on how much energy we have on that cellular level and how everything in our environment affects us on that level. Jay Feldman: That's basically, it's a lens through which we can view everything from nutrition to exercise and sleep and medications and learn from there. Jayton Miller: Definitely. So whenever we're categorizing things as far as healthy versus not healthy, anything that is not healthy would be interfering with the production or utilization of that energy, correct? Jay Feldman: Yeah. Yep, exactly. And of course, that gets a little complex. It's not always that easy to determine. And as we'll talk about today, there's a lot of things that might cause a reaction that leads to increased energy in the short term, that doesn't necessarily mean it's helping it in the longterm. It can get a little bit complicated, but it's normally the immediate effect on that energetic level will, as you said, determine whether something's helping us or harming us. Jayton Miller: Definitely. One of the things that I really wanted to talk about was the misconception around adaptation and hormesis. So can you give us a brief overview of some of the misconceptions that you've seen and experienced? Jay Feldman: Yeah. And just to define hormesis to start, which is a little bit tricky because there are a few different definitions that's morphed over the years to fit whatever narrative is being pushed. But initially, it was just this idea that giving a small amount of something that's very toxic, something like mercury or cadmium or radiation would lead to a defensive reaction in an organism, and that would lead to some health benefits. And this actually came about with a lot of industrial influence and trying to show that maybe radiation isn't as harmful as everyone's saying it is, and maybe polluting the environment or having these toxins in our food isn't such a big deal, maybe these things are actually helping us a bit. Jay Feldman: I don't think that's the case, but anyway, from there, it's morphed into this idea that anything, even if it's something that's not necessarily poisonous anything, that causes any amount of stress leads to that same kind of defensive reaction and adaptation, and that that's beneficial in the longterm. From there, it's even more further to become a very generic term that just means anything that can be good in small doses and bad in big doses or vice versa. And again, I think that's another way that this definition is morphed to make it sound like this is a very viable idea. Jay Feldman: But anyway, that second definition that anything that causes stress, a small amount of stress, is beneficial, is very commonly known and is applied to a lot of the low carb-dieting, it's applied to certain supplements like resveratrol and certain compounds like nitric oxide. And it's also applied to things like fasting and caloric restriction, where there's a lot of research and a lot of people in the health spaces saying that... Or another one is cold thermogenesis, dropping in some cold water, where there's this idea that giving your body a small amount of stress leads to some beneficial adaptations and makes our bodies stronger. And while there is some validity to it, I'll explain why I don't think it's really an accurate way of looking at things, and actually leads us down this path of thinking that, again, anything that causes some amount of stress is beneficial because it causes stress. Jay Feldman: And I think it's a relatively dangerous idea because obviously a lot of very harmful things because stress. And so I think there's some important clarifications to make there as far as why something might be helping us and also be causing stress at the same time. Jayton Miller: Definitely. I had Billy Craig on an interview yesterday, and I was talking to him about how they've seen older people who have lower metabolic rates and less energy utilization are able to live a little bit longer. But he was saying that if you actually look at the amount of calories they're using per unit of mass, their metabolic rate is actually phenomenally high. So whenever you're looking at those studies, it's usually a little bit jaded, I guess, a little bit in its perspective. So it's interesting that you touch on that. But in terms of hormesis, I've always seen it in the context of adapting to things as far as a performance perspective, so being able to run a mile and then adapting to that, being able to run two miles and things like that, which obviously endurance training is the opposite of what we want. Jayton Miller: But I've also seen a lot of benefits in the realm of the hormetic response to exercise, specifically resistance training. So I would definitely like to dive into that a little bit further as far as why that might not be favorable, and then some of the things that we can do in place of that. Jay Feldman: Yeah. And just to clarify too, adaptation is a part of what's considered to be hormesis or the hormetic response, but we can also adapt to things that are not hormetic or adapt to aspects of things that are not the stress. So just for the definition sake, I would say hormesis is adapting to the stress itself, whereas we can also adapt to other aspects of any stimulus. Exercise is a good example there where I do think that there are benefits to exercise, and those do come from adapting to that stimulus. But what I'll be arguing is that the adaptation is to certain effects that are not distress. Jay Feldman: When it comes to exercise, for example, you mentioned resistance training, when we're resistance training, we're putting tension on our musculoskeletal system on our musculofascial system, and that causes all sorts of adaptations. And I think you can argue that in the right dose, that's beneficial, but what people are arguing instead, and sometimes will change the training programs around this idea that it's the stress that's actually beneficial and causing those adaptations. And so we need to work out to failure or longer is better. There's some other details there, but there's this important delineation between why it's beneficial. And again, maybe we'll dig into a little bit, I would argue that the stress is not the reason. Jayton Miller: What do you think that reason is? Jay Feldman: Yeah. I think in the case of exercise, I think it is those specific effects. And I think this is a helpful delineation to make. This started with Hans Selye. He was one of the preliminary researchers talking about stress and our response to it, our adaptation to it. And so when he evaluated a stimulus, basically everybody at this time was aware of this idea that any stimulus would have effects that are specific to the stimulus. So exercise causes the certain tension that leads to muscle building, whereas sunlight is going to because increased melanin production in the skin, and on from there. Jay Feldman: Basically, anything that we are exposed to in our environment has unique effects to that stimulus, one of the many things that he researched and discovered, but this is in regard to stress, one of the things that was most noteworthy is he determined that there was a general effect, a universal effect that all stimuli have, and this is what he called the stressor effect. And so he basically said, "Yes, there's unique things to exercise as far as our response to it and there's unique things to sunlight and toxins and infections, but there's also a universal component," which he called the stressor effect, which basically came down to the usage of energy. Jay Feldman: His terms here were adaptation energy and I think evolving on that. I think it comes down to that physiological energy we were talking about earlier. I think that's this delineation we need to make is, between specific effects and stressor effects or the usage of energy. And what he found was that when we have too much of those stressors, it causes all sorts of degeneration, and that degeneration is universal, whether it's too much like exposure to an infection or excessive amounts of exercise, or too little nutrition, all of those things, they have specific effects, but they have the stressor effect, and when we have too much of that stress compared to the energy we have available to handle it, it causes all of this degeneration, all of these chronic health conditions that he did a pretty good job of mapping out. Jay Feldman: And again, with this idea of hormesis, people have taken this to say that that stress, the stressor effect, is actually what's beneficial. And you'll hear this pretty often, which is that we're looking for certain end points like autophagy or mitochondrial biogenesis, or some sort of stimulation of mitochondrial respiration that these increases in lifespan, that these are all things that happened in response to small amounts of stress and that they're beneficial. And the way that this has done has to do, basically on the physiological level, with... The stress comes down to a lack of energy and the production of reactive oxygen species. So any time that we're lacking in energy or energy-producing systems are disrupted, we have this increase in reactive oxygen species. Jay Feldman: And again, from that view of hormesis, that's why exercise is beneficial, or that's why cold thermogenesis is beneficial. In the case of cold thermogenesis, you're activating stress that's somewhat unique to temperature, you've got the heat shock proteins and all of that. But it all travels through this same generalized pathway that Selye was referring to, which has to do with the production of reactive oxygen species and the activation of all of these signals that are saying that our body doesn't have energy. AMPK is one of the main ones there as well. You've got the whole Nrfs and JNKs, all these basically inflammatory pathways, all of these pathways that are activated when we're starving or when we're under considerable stress.  Jay Feldman: And again, from this hormetic view, small amounts of those things lead to all these supposed that benefits, it leads to autophagy, it leads to mitochondrial biogenesis, meaning you're producing more mitochondria so you should be able to produce more energy. And with autophagy, is the idea that you're clearing out like damaged cells or debris. So these are supposed to be good things. And I'm not necessarily saying that those are bad things, but I think that there are better ways to achieve them that don't require this depletion of energy, even in the short term and the stress that's caused. Jayton Miller: So do you think that there's a threshold that we can meet? And do you usually differentiate what would be under that threshold as eustress and then above that being distress? Jay Feldman: Yeah. I'm glad you brought that up. I don't think it's a threshold problem, but I think it's an important thing to bring up. So there is this idea of eustress and distress, and this was these word terms that Hans Selye used. And eustress was something that was stressful, but was still beneficial, and distress was something that was stressful, but was overall harmful. And those are important distinctions to make, but my problem with that language is that it makes us think that it's just the amount of stress that matters, and that's what you're saying with this threshold, where it's eustress if it's below a certain threshold and it's distress if it's above a certain threshold. Jay Feldman: And I think a better way to look at it is that it's eustress or it's something that's beneficial if the specific effects of that stimulus outweigh the stressful effects. So what I would say is that the stress is always going to be harmful. Basically, you never want to be doing something that's going to disrupt our ability to produce energy or deplete excessive amounts of energy, drive this excessive reactive oxygen species production without enough energy. I'm going to say that those things are never ideal, there's always a cost there, there's always some harm there. Jay Feldman: And I think that makes sense that when we zoom out a bit and think about our adaptation to that, where an adaptation to something that's harmful, it does tend to improve our ability to handle things that are harmful, but it also comes at the cost of degrading ourselves where more used to that. So this idea, I guess I would say, as far as the threshold is not related to how much stress, but rather whether these other effects of these stimuli are beneficial enough to outweigh the stressful effects. So reduced fasting as an example, a lot of people find benefits on fasting, and we also know that that's universally stressful, it's basically a short term starvation. Jay Feldman: And what I would say is that the people who are finding benefits from fasting are finding benefits from those specific effects, and those specific effects would be, you're no longer getting any food in your digestive tract so you're not producing any endotoxin or feeding any pathogens in your gut so you've found a lot of relief there. Or maybe if somebody is eating a lot of foods that are relatively toxic, whether they've got a bunch of additives and preservatives in there, or a bunch of anti-nutrients or whatever it is, they're not eating those anymore, so that's going to bring some relief. So those things might lead to somebody's feeling better in that case and at the same time they're still having that stress from the short-term starvation. Jay Feldman: But I would say if you're noticing benefits from fasting, it's most likely because those specific effects outweigh the stressful effects. And so I would say that that's a better way to look at something like eustress, although, again, I don't like the definition because it's not about the stress necessarily. But what's important about that delineation is that we don't always have to make that choice.... We don't always have to take the bad with the good, we can have those beneficial, specific effects of not irritating our gut and of not taking in toxins without the stressful side of fasting. Jay Feldman: So that's some of the application of this anti-hormesis idea, is that you can still have a lot of those benefits from these interventions without the excessive stress. And that's what you mentioned too, as far as exercise goes, where you could have resistance training versus like long-distance cardio, and that both of those, you're going to have some beneficial effects or are going to have some stimulation of the muscles. And they're not the same, it's a crude example, but in one, you're going to have excessive amounts of stress and the other, you have much less, you have much less of an energy drain. Jayton Miller: Definitely. What are some of the things that people can pay attention to to know whether or not the benefits that they think that they're experiencing are actually beneficial to the organism? Jay Feldman: Yeah, that's a good question, and maybe this is what you're getting at, is that sometimes when we're doing things that are really stressful, they might feel good because we've got a lot of adrenaline coursing through our veins and that feels pretty good, it feels like we've got a lot of energy, even though it is coming at a pretty major long-term cost. It's not always really that easy to determine. In the long-term, we always find out, but of course it's helpful to know in the short term. Jay Feldman: There are some indicators that I think can be helpful, and the biggest one is how you feel, but it's not only if you have energy, but are you able to sleep? For example. So a lot of people who go to low carb and know that they have a lot of that, well, they don't know that they have adrenaline, but they feel like they've got good energy, but at the same time, they can't sleep at night, they can't stay asleep, they can't sleep through the night, they can't fall asleep. So, that's a good sign of excess adrenaline. Of course it's not always quite that clear cut either where things are improving, everything is automatically better. Jay Feldman: But in general, using any symptom that would see is helpful, how well is your brain functioning? Do you have a calm energy or more of a manic energy? Again, are you able to rest and relax and go to sleep? Do you have any digestive symptoms? Temperature can be another good indicator where if our temperatures are elevated due to stress hormones and then we eat some carbohydrates and our temperatures go down, that's what we would see. Whereas, if you don't have high stress amounts and you need some carbohydrates, your temperature should stay the same or go up. So, that can be a good indicator too. Jay Feldman: But part of the other side of this, as much as experience is really helpful, also understanding, I think, the physiology is helpful too. So you have that combination there of an idea of where we should be going and what we should be looking for to make sure that we are not just feeling good because of these short-term stress hormones. Jayton Miller: Definitely. I noticed that for me personally, whenever I cross that line, I guess, to a little bit too much stress, my digestion is the first thing to go. As soon as my digestion starts to mess up, I know that I need to take a step back, examine what I'm doing, slow down, rest. And then I also find that my fingers and my toes will freeze up almost immediately on a daily basis. So I also watch that very closely. Jay Feldman: Yeah, that's a perfect indicator, hands and feet being cold, which can happen even if your temperature is relatively normal, but that's a really good sign of stress hormones. Yeah. Jayton Miller: Definitely. So do you ever take into consideration the possible epigenetic factors that come into play with hormesis as well? Jay Feldman: Yeah. As you were saying earlier, hormesis and adaptation go hand in hand a bit, and I think that there are some important misconceptions with adaptation too. It's the same idea where it's like if we adapt to something that's harmful, we'll become stronger, we'll become better at dealing with it. And again, that does tend to happen, we become, you could also say less sensitive to it. And this is very clear when you look at some of the organisms that they do these studies on. One of the most common ones is C elegans, which is a worm, a very, very small worm. And what they find is that when they put it under a lot of stress or small amounts of "hormetic stress", it does live longer and it has this lifespan extension. Jay Feldman: And that's cited all the time as a support for caloric restriction or support for any other sort of hormesis. And one of the really important components there that's not normally acknowledged is that C elegans, when it's under stress, enters basically a hibernation state called douer. And in that hibernation state, it's not functioning like it normally would, instead, its entire body switches towards the stress system, it starts to run on fats instead of glucose, it starts to down-regulate the amount of energy it's producing very significantly. And I don't think it moves around in the same way. It's basically not even viable where it would be very hard for it to survive in the wild, but because it's in a lab, it can survive longer. Jay Feldman: So you have this adaptation to stress and it's allowing for extended life and it's better able to deal with all these stresses, but it's because it's not really living, I mean, it's function is so degraded. I think that's a good picture to consider when we're talking about adaptation, whether that adaptation is happening within a lifetime or down hereditarily and to future generations. And again, you mentioned epigenetics, and that is where that's coming into play. I mean, we're turning on and off different genes and activating all these various proteins. And I think the biggest factor to consider here is that big picture, where when we are adapting to things that are harmful, we become better at handling harmful things at the cost of higher structure and greater complexity. Jay Feldman: And so there are a lot of epigenetic adaptations to that, and we see that in humans, when we look at what's happened in populations that had significant starvation and then you look down the line and they're more prone to obesity, the children are. And beyond rat and cat studies where they've put them under some stress and then they look a couple of generations down and they see that there's degeneration going on. So there are epigenetic effects too when we're adapting to anything, whether it's bad or good, but when we are adapting to this harmful things, I would say that they're generally negative. Jay Feldman: And part of the problem here is that, I know I talked about autophagy and mitochondrial biogenesis as a couple of those main things. I don't see those as harmful. It is seen that in chronic health conditions and diseases, there are defects in autophagy and it is seen that... But at the same time, what's important to consider too, is that in those diseases, there's also excessive stress, there's also excessive reactive oxygen species production. So if we're under this idea that a small amount of stress is good and leads to these benefits yet excessive stress leads to defects and these sorts of autophagy and adaptations, I look at that as a good example for the fact that we want those adaptations to be working properly. Jay Feldman: We want to be able to increase autophagy when we're exposed to stress. And if we drive too far in that route, we lose our ability to adapt. But rather than wanting to stimulate autophagy directly by causing stress, we can actually do it through alternative means. And again, it comes down to some of the biochemistry here and some of the details, but we also end up seeing reactive oxygen species production when we're producing a lot of energy as like a breaking mechanism. That's normally why it's down in the first place, is that when we're under stress and we're not able to produce energy efficiently, we turn off that system because if we produce too many of these reactive oxygen species, we end up with a ton of damage and destruction, so it's like this alarm signal. Jay Feldman: But the signal also happens if we're producing a lot of energy and we have enough where we have this excess of end product of ATP that's stopping everything up earlier in the line, and that also leads to reactive oxygen species production and stops or slows down respiration, switches it over to fat oxidation and slows it down with all these braking systems. But in this case, there's a major difference, which is that we're protected by the higher levels of ATP and higher levels of carbon dioxide and the higher energy state of the cell. And that protects us against any damage from the reactive oxygen species and allows us to still have things like mitochondrial biogenesis and autophagy and improve our ability to not adapt to harm, but actually improve our capacity for greater energy and greater structural complexity, but without any of these other signals that often come in the form of stress hormones. Jay Feldman: When you have the high reactive oxygen species and low energy, you have the AMPK signals going on, you eventually have adrenaline and cortisol going on. And those all lead to long-term depression of thyroid and prometabolic hormones. Whereas when you have high energy and elevated reactive oxygen species, you don't have all those stress signals. You just have those adaptations that we're looking for that are defective in these chronic diseases, but without the harmful effects that lead to all those partially epigenetic adaptations and also non-epigenetic adaptations, but it's a major difference just that the presence of energy and the lack of presence of those stress signals. Jay Feldman: And I would say that that's really where we see the major difference physiologically between something that we're adapting to that's stressful and harmful and requires us to conserve energy and decrease our structure so we can handle whatever's there as opposed to something that supports us energetically, allows our bodies to say, "Hey, I don't need to conserve energy right now, my environment's great. I can kick up all of my functions, my thyroid function, my reproductive function, my digestive function. I can send blood out to my hands and feet so that they can stay warm as opposed to needing to keep them in our internal areas or internal organs, so that way they can stay warm." All those things that go together and support that higher energy state as opposed to driving towards the lower one. Jayton Miller: Definitely. Do you think that that is responsible for the association that people see between calorie surpluses and inflammation? Jay Feldman: Meaning the high energy, but also some reactive oxygen species production? Jayton Miller: Mm-hmm (affirmative). Jay Feldman: I don't know about that. One other factor when it comes to caloric restriction and caloric surplus is what are the foods. And I think that's a major issue when it comes to all a lot of the caloric restriction researches, they found that, yeah, there's all these benefits there, but you also get those benefits when you just restrict the inflammatory amino acids. You also get those benefits when you reduce endotoxin, and you also get those benefits when you reduce PUFA. And all of those things are shown to be correlated with lifespan and disease. So I guess you could flip that too with the caloric surplus where the question is, is it the caloric surplus, or is it what those calories are made up of? Jay Feldman: I think that that's more of what it is, we have a defective metabolism and you add in more fuel to that fire as opposed to a well-functioning metabolism, or when you add more fuel, it just keeps it running, it keeps it running at a higher level. I don't know what if there was something specific you were referring to as far as caloric surplus and inflammation, but I think when it comes to like the rat research and stuff like that, I think that's more of how I would see it. Jayton Miller: Definitely. No, that answers my question perfectly. One other thing that I'm curious about is, what if somebody is trying to strengthen the buffer that they have to the stress over time, whether it's increasing work capacity for a certain amount of exercise to take place, or just increasing their buffer on a daily basis to the stress that they face? Jay Feldman: We have, again, these two paths here around, one path it's getting used to the stress more and getting more acquainted with it, versus on the other side, when we're supporting the energy producing systems, we also end up with a greater energy pool, a greater energy availability, which means that we have more to pull from before we're causing stress. So I would prefer to go that latter route. And as far as how that looks, some of this does come down to specific effects too where you are strengthening your muscular fascial system, those connections and the strength there. Jay Feldman: And there's actually a couple different types of muscular building, and one in particular tends to go more of a stress, and the other tends to go more with lower stress. And that one with the less stress has to do with more protein building whereas the other one has to do with more swelling and increased resources, more fuel in the muscle cells. And so that protein moments is the mild fibrillar. I would say that those adaptations are going to happen due to the specific effects, for example, if you're lifting weights, because you are adapting to that stimulus, you are going to have improved, increased protein concentration in those areas, building up that protein of the muscle cells. Jay Feldman: You're also going to have increased neuromuscular tone and ability to contract, contractility there, which is actually one of the main factors responsible for increases in strength when people first start working out. When you watch someone work out and they go from only being able to bench 20 pounds to 60 in six weeks, that's not because they put on all this muscle, of course, they might be putting on some, but most of it, it's a neuromuscular connection. So those things are all strengthening and those are independent of stress, they're just specific to the stimulation. Jay Feldman: So I would say that that's really what we want to be going forward when you would want to be improving work capacity as opposed to improving capacity towards stress. So I guess another way I would say it is that, I think it's more ideal health wise to be trying to improve our capacity for something like strength than to be able to handle something like excessive stress. So I think that the only way you're going to improve your ability to run super long distances is to create adaptations to that stress. I just think that there's a cost there. If somebody wants to do it, that's fine, but I think we want to recognize that cost there too. Jay Feldman: And you can minimize that cost by improving your resilience distress, making sure you're getting a lot of fuel, all of that, but there is a cost just by wanting to adapt to that. If we wanted to adapt to living in the Tundra, we can, people do it and they have epigenetic adaptations, genetic adaptations, all sorts of really interesting things, but it also, I would argue, comes at the cost of less structural complexity in the long term. So it depends on what we're trying to adapt to, but in the case of specifically work capacity, it depends on if it's more dependent on strengthen and function as opposed to needing to deal with stress and resilience. Jay Feldman: One other factor there too is economy. So with runners, for example, they become more economic with the way they run as they continue to practice, so they end up having less stress and requiring less energy to do the same amount of work. So that's another factor there too that will improve just by continuing to adapt to those things. Jayton Miller: Interesting. Whenever it comes to resistance training specifically, do you tend to see a difference between eccentric and concentric muscle contractions? Because I believe within the concentric part of the contraction, there's an anabolic effect with a testosterone response and then the eccentric effect is a catabolic response to the cortisol response. Do you have any tips there? Jay Feldman: Yeah. And of course, you can't always minimize one or the other. A lot of movements have aspects of both, but I do think that the eccentric leads to more of that stress response and adaptation which can lead to big muscles, but it doesn't mean they're necessarily functional muscles, it doesn't mean it's overall as healthy. So I do think to whatever extent you can, I guess, you could say favoring the concentric another way to put it would just be not doing focused eccentric work where you're going super slow for four seconds down or whatever. So I do think probably just not focusing on the eccentric is better for health. Jayton Miller: Yeah. What about the ability to increase mental capacity or the ability to work more with the mind rather than physical? Jay Feldman: There's this funny study when I was looking for all the hormesis research where they were saying that, "Hey, this applies to the brain too. When the brain is under stress, it responds and improves its capacity." And one of the studies they cited was looking at elderly people in some retirement home or nursing home or something. And it was saying that when they're reading books and playing cards, their neurological capacity is increased. And they were saying that was a sign of hormesis that these things were causing stress. It just goes to show how much they've morphed this definition and how convoluted it's become. But that I don't think that those things are quite all that stressful. Jay Feldman: And I think that to attribute those benefits to the stress caused by playing cards, even the physiological stress, I think is ridiculous, but I think it applies in the way where stimulating those neurological connections in whatever capacity, I think, leads to adaptations that leads to improvement there. Some people have the same idea where if you don't use it, you lose it, and I don't necessarily agree with that. I think that having improved brain capacity is a part of improved complexity. And considering that, I think, that it should be something that improves, I guess, even if you weren't stimulating it, but I don't know how that would work, it's not like something you could see in practice. Jay Feldman: But I do think having stimulation is good. For example, if we're under a lot of psychological stress, I don't think that's going to be leading to us becoming smarter, for example, I think it will lead to you maybe getting more "resilience." Sometimes that, again, comes at the cost of being able to tap into your emotions or being able to think real clearly or think about higher level things. We will adapt to that stress, I don't think that's what we really want to be going for though. I don't know if that answered your question. Jayton Miller: Definitely. Yeah. I think this was also one of the things that I talked about in my conversation with Billy, he said that during starvation periods, the brain can shrink up to 2%. So if you're in Kellogg restriction, the brain actually shrinks to where you only have the capabilities of the more primordial parts of the brain and the complexity and abstraction diminishes as the brain shrinks in size, which makes a lot of sense. It's also interesting. Have you seen any of the research in regards to the brain taking up 80% of the metabolism whenever it's in states of basically like a flow state? Jay Feldman: I haven't seen that. Interestingly, I was looking into that and then some of the research that I've found, which there's an all that much was actually saying that whether our brains active or not it ends up using about the same amount of fuel or the same percentage of fuel, I don't know if that's... I'd be interested to see something that shows otherwise for sure, but I haven't seen that, but it wouldn't surprise me if there was some uptake in activity, even without any increase, our brain already uses, I think around 20 to 25% our total caloric needs, if you want to think of it that way, but just our total fuel, which is of course, a massive amount proportionately. I think proportionately, it's only about 2% of our total body. Jay Feldman: So as far as caloric restriction and brain health, that definitely doesn't surprise me, that it would shrink and capacity would shrink. If you look at the Minnesota starvation experiment and what happened to their mental capacity when they were eating 1,800 calories a day as opposed to the regular 3,300, maybe 1,600 calories, they were not the same people at all. A lot of them were failing their classes or weren't even able to go, they couldn't hold up relationships. They had no sense of humor, they had no interest in sex, they had no libido. And it went beyond that too, some of them had psychotic breaks. Jay Feldman: When you talked about more primordial things, some of them ended up stealing food from trash cans. It completely changes our mental capacity, that's for sure. Jayton Miller: Definitely. I guess taking another direction for a second, one of the things that I would like to get your opinion on is the adaptation that we have to becoming a fat burner versus utilizing glucose as fuel. Can you take us through that transition and why it might not be favorable? Jay Feldman: Yeah. In line with that bioenergetic lens, I think it always makes the most sense to start on that energetic level and what's actually happening there. Basically, I would say that fat is much less efficient as a fuel, and there's biochemical reasons for that that I'll mention. And also, there's other evidence to support this, just the idea that our brains can't use fat, they have to rely on glucose or ketones, which we'll get to ketones. But the short of it just looking at sugar versus fat, fat will cause way too much reactive oxygen, species production, and it cause too many breaks in mitochondrial respiration to be supportive of our brain energy needs, which as we said, those energy needs are pretty high, and so it's a good model to look at as far as what things look like when they need to function well. Jay Feldman: Whereas other areas of our body can deal with lower energy. When we're looking on that biochemical level and that physiological level of what's actually happening when we use one versus the other for fuel, when we use glucose for fuel, assuming that we've got the nutrients we need, there's no brakes on the system from polyunsaturated fats or endotoxin or anything else, everything runs very smoothly, quickly, there's nothing stopping that process unless we produce so much ATP that we don't need any more. We produce a lot of NAD, which keeps our NAD to NADH ratio high, which keeps the electron transport chain functioning well. Jay Feldman: We also produce a lot of CO2, which helps to increase oxygen offloading into the cell, which allows for further increased respiration. So it's a very cohesive system that basically allows us to produce a lot of energy. And when we have fat metabolism, we basically have the opposite. And there's very good reasons for that, you mentioned adaptation where basically we need to have some system that allows us to put on the brakes, for example, if we're not eating. If we're not eating carbs, that's one thing, but low carb metabolism is the same as starvation metabolism. And when that happens, when we're starving, if we adapted to starvation by increasing the amount of energy we use, we will not last very long when we starved. Jay Feldman: So because of that instead, anytime we're in a suboptimal environment, but starvation is a pretty rough one, we have to slow down how much energy we're using, stop our thyroid from functioning as much, stop our reproductive hormones, slow everything down. We can deal with the cold hands and feet, so that way we can survive. And so fat metabolism is basically the perfect picture of that, where there are a couple of differences. One is that there's less carbon dioxide being produced, which means less oxygenation, which is one way that there's this break on the system. The other one is that we have a lot more, FADH2 being produced. Jay Feldman: Basically there's some competition in the electron transport chain between the donation of electrons from NADH and the donation of electrons between FADH2 where they both use the same... They basically both rely on ubiquinone availability, and so when you have a lot of FADH2 donating electrons, it slows down the drop-off of electrons from NADH and leads to a buildup of NADH, which decreases the NAD to NADH ratio. And that then has effects all throughout, like higher up in the energy producing processes to slow things down because the availability of NAD helps to drive, basically speed things up. Jay Feldman: And so when you have this excess NADH, it puts all of these other breaks on the system which happens during fat metabolism. And that's another way that things are slowed down on that immediate energy level. And it also increases the production of reactive oxygen species at the same time, which leads to some of those adaptations we talked about earlier. It does lead to autophagy, it does lead to mitochondrial biogenesis, these kinds of backup pathways that are there to help us survive these, in this case, they're there to help us survive these rough times. So starting from that energetic level. Jay Feldman: And it's important to note here too, whenever we look at something like fat metabolism in the short term, you see those breaks, you see the slowing down of respiration, then there's always an adaptive effect, I mean, it is an adaptation, but there's always a rebound effect where if your body is still needing to function, at first, it's like, "Hey, I still need energy." And it basically has all these backup pathways, and one of them is through sirtuins or SIRT search. But sirtuins are known as like longevity promoting proteins, but it's basically a backup pathway to fix the low NAD to NADH ratio from fat metabolism and any other stress. Jay Feldman: So you have the activation of all these backup pathways to bring that NAD to NADH ratio back up so you can still produce energy, especially in the short term our body's like, it might be a little bit of stress, but we can get through it. And so initially, you see this dampening effect and then a rebound effect, and then in the long term you just see the dampening effect, it just has that long-term cost. But again, that short-term rebound is why some people say it's beneficial, but again, I would argue that, you still have the long-term effect too which is just smaller. And if you continue for longer period of time, it's going to show, even if you're doing it for a short period of time, you're not going to have a benefit, you're just going to have that stress hormone response. Jay Feldman: And that's another part of it too, that's why people sometimes will feel good when they switched to fat metabolism, they've got that adrenaline going. That's where all those kinds of adaptations start, and then again, big picture we have the increased stress hormone production, which is the mediator that tells our bodies things are not good right now, if this continues for any longer, we have to start shutting everything down. And so that's eventually what you get when you're adapting to fat metabolism and fat burning. Jayton Miller: Yeah. We tend to call that the catecholamine honeymoon, that first like 30 to 60 days where people feel really good, and then after that, it's usually pretty downhill. Can you go through some of the similarities that fat burning state has with caloric restriction? Jay Feldman: Yeah. Basically, they really mimic each other where if we don't have any food, we start to shift in the same way. So anytime that we see energy depletion starting on that cellular level, we have the activation of all of these signal, AMP kinase, which is saying there's no ATP around. You've typically got reactive oxygen, species production, which says that there's some kind of stress or damage. And it activates all these pathways that activate stress hormones, and those stress hormones lead to a couple of things. For one they decrease.... Jay Feldman: In the short term, some days they'll increase... The first thing will try to do is increase glucose release from the liver. So that way we can still maintain some glucose metabolism. If that is not enough to immediately solve what's going on, then they'd say, "All right, we've got to start increasing fat metabolism." You start to pull fat from our body fat stores. If that's still going on and that's not enough to deal with that immediate energy problem, which is nonstop, if you're starving or caloric restriction, like just minor starvation, it's going to keep happening. Jay Feldman: And then if it's so much to the point that there's still not enough food available, especially for the brain, if there's not enough glucose, they'll start to lead to ketone production and liver, which again, is driven by stress hormones just as part of that backup system. So you basically have the same response, it's just a matter of to what extent. Sometimes it can be to a much greater extent with low carb versus just a small amount of caloric restriction, it depends, but in both cases, you're having the same stress responses that are happening due to the low energy on that cellular level, leading to those stress signals, leading to the bigger mediators being the stress hormones, glucagon, epinephrine, cortisol, and then eventually, it continues branching out from there. Jayton Miller: Interesting. One of the things that I was curious about is how people tend to see an increase in insulin sensitivity whenever they're in a caloric deficit, but at the same time, from a logical perspective, to me, the increase in the amount of free fatty acids in the blood would lead to more of the Randle cycle happening. So do you know what's going on in that pathway right there? Jay Feldman: Yeah. There's a couple of things. One is that insulin drives down the stress hormones and drives down free fatty acids, and so glucose partially by stimulating insulin production. So if you're starving and then you take in some carbohydrates, that's going to increase insulin, drop all those stress hormones, stop gluconeogenesis, stop all that fat release and drive down free fatty acids and allow for the uptake of the glucose. So it's basically like, because you're in that low fuel-stress state, you're more ready to take up the carbs. Jay Feldman: And the same thing happens, even if we're just fasting overnight, which we all do when we sleep, it's much less stressful because our demands are much lower, but that's why when we wake up, we tend to be pretty insulin sensitive too and we tend to have a lot of carb cravings. And the same thing is after we exercise, basically when our carbs are depleted, we're very sensitive to our need for more carbs. And it's still mediated through those same stress hormones, but basically, you have this dropping of stress hormones very quickly and dropping of free fatty acids. The other thing too is that free fatty acids are part of it, but it also has to do with the ability to uptake glucose. Jay Feldman: I think in some situations, high free fatty acids are more correlated with insulin resistance rather than being causative. It is true that with the Randle cycle, you only have basically one choice, you're either using fat or carbs and both prevent the other from functioning at the same time in one cell, not necessarily throughout the body, but it can switch back and forth very easily. And if the cell is basically very low on glucose and able to metabolize, it's going to be taking it up and switching right back over if it has it available. Normally, the problem in insulin resistance is not high free fatty acids first, normally there's something else blocking its ability to use carbs. Jay Feldman: So then we have to increase free fatty acids as that backup pathway. And yes, then it's just focusing on free fatty acids as its fuel, but once our carb metabolism is somewhat fixed and you've got those carbs available, it's going to switch it back. Jayton Miller: Okay. Interesting. What is your perspective on being fat adapted? So the ability to flirt with that line and jump back and forth across it. Jay Feldman: It's funny just because there's this idea, being fat adapted and metabolic flexibility too where... The thing that I think is funny there is the idea that you have to do something in order to be able to metabolize fats, but that's our default backup state. Nobody is just running on carbs because they can't run on fat, if anything, it's the other way around, they would be just running on fat because they can't run on carbs. Carbs, there's a lot more factors that can be limiting it and if you're low on energy, you're always going to be tending towards the fat side anyway due to all those stress signals.  Jay Feldman: So I would say that fat metabolism is that default backup state. And again, that doesn't mean that we can't be using any fat at any time and that that's always a bad thing. For example, our muscles don't need a lot of energy when they're just hanging out when we're just at rest, and so they're fine using the decent amount of fat. And fat is used for various other things too, so I'm not anti-fat, I just think it's just not as good at producing high levels of energy in short period of time. I think normally when people are talking about that, it more really has to do with impaired carbon metabolism and often there's some gut issues there, but we should always be able to use either fuel, but as we've talked about, we don't really want to adapt to using fat as our main fuel, there's a big cost there. Jay Feldman: And just because we can do it, it doesn't mean it's good for us in our long run or good for our descendants and the human species in the long run. I think that that's going to lead to a lot of adaptations to basically having less energy, and those don't tend to go in the direction that we want them to. Jayton Miller: Definitely. I completely agree. Well, Jay, I won't take up too much more of your time today. I really appreciate you hopping on here and talking to everybody. Where can people find you and follow you and stuff like that? Jay Feldman: Yeah, yeah, Thanks for having me. That's fun. My website is Jayfeldmanwellness.com. I've got a bunch of articles like free things on there. And a couple of those articles are dealing with hormesis. They're pretty long and really digging into all the research for anyone who's interested. And then I also have a podcast called The Energy Balance Podcast. You can find it from my website or you can just search it anywhere that you listen to podcasts. And yeah, check it out. Jayton Miller: Heck yeah. Sweet. Well, for all those who listen, make sure to check out his podcast because I personally do listen to it consistently on Spotify, so make sure to check it out. I enjoy it and I know you all will too. You have a good one. Jayton Miller: Thanks for listening to the podcast, if you haven't already, make sure to hit the Like button, subscribe and leave comment down below if you want us to cover a different topic.

I believe all of us worldwide are ready for the coronavirus to be over. Austrian-Canadian scientist Dr. Hans Selye wrote a total of 30 books in his quest to better understand stress and human emotion. Toward the end of his life, Dr. Selye summarized his research, declaring that anger, bitterness and revenge are the emotions most harmful to our health and well-being. He also concluded that a heart of gratitude is the single most nourishing response that leads to good health. Gratitude and thanksgiving are like therapy for the soul. In this holiday season, much emphasis is placed on thanking God for the positive blessings of life. And we should. But how should we respond to negative circumstances when storms blow into our lives?

"Good psychology should include all the methodological techniques, without having loyalty to one method, one idea, or one person," ~ Abraham Maslow In honor of International Stress Awareness, this week's PTSD and Beyond Podcast Episode, Mark Gruesbeck, MA and I cover 6 "Greats," Abraham Maslow, Hans Selye, Carl Jung, Bessel Van Der Kolk, Alan Watts, and Louise Hay.  Each of these folks bring a unique perspective on the affects of stress. We've chosen them as collectively they bring a holistic view covering affects of stress on the body, the mind, the emotions, and energy."It's not the stress that kills us, it's our reaction to it." ~ Hans Selye What are some affects of stress? What can we learn from Selye's research and works? We cover nuggets of Selye's work and how Van Der Kolk continued that work and further showed how the body keeps the score."What you resists, persists," ~ Carl JungJung further teaches us that stress is like a boomerang when we resist it persists. How do we then "let go" of stress? What can we do to resist stress? "To have faith is to trust yourself to the water. When you swim you don't grab hold of the water, because if you do you will sink and drown. Instead you relax, and float,” – Alan Watts.According to Watts, there's a beauty of not grabbing on and holding on to stress and including anxiety. His point is illustrated with the above quote. Just as much as we cannot grab the water, we cannot grab stress. Instead we relax and float through. "Stress is a fear reaction to life and to life's constant changes," Louise HayHay brings another value of her applied work in her book, You Can Heal Your Life, identifying affirmations linked to dis-ease and emotional distress. We provide Hays 10 affirmations bringing an additional lens into stress relief and Be-ing. The PTSDandBeyond Podcast is listened to in over 50 countries and available on Amazon Music, iHeart Radio, Spotify, Apple Podcasts, Podbean, and other favorite podcast apps!Thank YOU for your continued support of PTSD and Beyond; with every Ko-Fi and swag purchase we can continue to bring  this valuable resource and for the humbled honor to continue building our communities!Subscribe, Download, Listen, Share, and Comment! 

This week, Dr. Broderick will talk about: Stress. Sensors, Synapses, Serotonin, Syndromes and Sadness Dr. Broderick will touch on and the audience will pipe in...Helplessness-Have you felt helpless?Hans Selye_ Birth of Stress - The American Institute of Stress.html Although Selye was fluent in at least eight languages, including English, and could converse in another half dozen, his choice of "stress" to describe the non-specific response syndrome he discovered, was unfortunate. He had used "stress" in his initial letter to the Editor of Nature in 1936, who suggested that it be deleted since this implied nervous strain and substituted alarm reaction. He was also unaware that stress had been used for centuries in physics to explain elasticity, the property of a material that allows it to resume its original size and shape after having been compressed or stretched by an external force. As expressed in Hooke's Law of 1658, the magnitude of an external force, or stress, produces a proportional amount of deformation, or strain, in a malleable metal. Selye several times complained that had his knowledge of English been more precise, he would have gone down in history as the father of the "strain" concept. The term, stress, is only fifty years old. why are the healthy and the unhealthy affected the same way?how Dr. Broderick provided the data to the FDA for the use of alprazolam for anxiety and depression.Alprazolam-the inherent healeradinazolam.- its sisterThe Serotonin SyndromeThe Cytokine StormBroderick Lab goes to London!They take the notes on Covid with themThe BRODERICK PROBE-it can take the immune system and transduce this system through the endocrine system straight to the brain Does India have no stress?The COVID-19 infection rate in India remains low relative to population size.Some credit fast government action to quarantine people and shut borders.Response is "impressive" says the World Health Organization.But officials are still preparing for broader outbreak and community transmission. India reported its third death from COVID-19 on Tuesday.Notes on the Mikovic "Plandemic"When will the pandemic end?

Episode 121 | John Kiely: Periodization Paradigms and Stress Theory Subscribe & Review on : Apple Podcasts | Stitcher Periodization. Strength and conditioning coaches and sport coaches use it to help their athletes progress and adapt - to get stronger, faster, and more powerful. But, what if the foundation of periodization has roots from somewhere else? What if periodization was never intended for sport at all? If I have tickled your curiosity then you are going to love this podcast with John Kiely. John is a strength and conditioning coach and currently work at the Institute for Coaching and Performance (ICaP), at the University of Central Lancashire. His current research interests revolve around human performance, and include: The detrimental effects of fatigue on running coordination; the modernizing of Periodization planning paradigms; stress as it relates to performance and health; genetics and sports performance; and the link between fitness, movement, cognition and emotional health. Enjoy this mind blowing episode! Part 1 | Periodization Paradigms and Stress Theory Overview of Periodization Paradigms and Stress Theory Historical significance from industrial revolution ala Frederick Winslow Taylor and how this came to be applied to other fields. Principles of scientific management “Selye once remarked that he never considered the application of his research to sporting domains” GAS - general adaptation syndrome Stress Paper; device.  Differences and commonalities between periodization philosophies Stress response and adaptation Part 2 | Where do we go from here? Path dependence   Zombie idea       How can we help coaches and athletes continue to progress? Inter individual variability (adaption across a group) Coaching and Individualization of athletes’ programs How you educate athlete about plan Degree of self determination Athlete needs to believe in training Self regulation; Autoregulation by PRE, RIR, Load/velocity HRV See Table 1 from Periodization Paradigms Show Notes: https://www.researchgate.net/publication/230756715_Periodization_Paradigms_in_the_21st_Century_Evidence-Led_or_Tradition-Driven https://www.researchgate.net/publication/321386054_Periodization_Theory_Confronting_an_Inconvenient_Truth

The conversation about flashcards continues in this third of three series about helping our students use retrieval practice in A&P. Advanced methods include stars & emojis, multiple cards, plus concept lists & maps. We remember stress expert Bruce McEwen and introduce our new sponsor: ADInstruments. 00:45 | Bruce S. McEwan 03:59 | Sponsored by AAA 04:40 | Flashcards: Stars & Emojis 15:07 | Sponsored by ADInstruments 19:25 | Flashcards: Multiples & Spinning 27:20 | Sponsored by HAPI 28:00 |  Flashcards: Concept Lists & Maps 37:05 | Sponsored by HAPS 37:49 | Survey Says... 39:13 | Staying Connected If you cannot see or activate the audio player click here. Please take the anonymous survey: theAPprofessor.org/survey Questions & Feedback: 1-833-LION-DEN (1-833-546-6336) Follow The A&P Professor on Twitter, Facebook, Blogger, Nuzzel, Tumblr, or Instagram! Bruce S. McEwen 3 minutes Bruce S. McEwen, renowned stress expert, died recently. This segment pays tribute to his contributions. The Rockefeller University » Neuroscientist Bruce McEwen, who studied the impact of stress on the brain, has died (obituary) my-ap.us/2R2vPc0 Mechanisms of stress in the brain (review article authored by McEwen, et al.) my-ap.us/2R4G2Vn The Brain on Stress: Toward an Integrative Approach to Brain, Body and Behavior (perspectives article by McEwen) my-ap.us/35HnWhF The End of Stress as We Know It (McEwen's book) amzn.to/36sHnvN   Sponsored by AAA 0.5 minutes A searchable transcript for this episode, as well as the captioned audiogram of this episode, are sponsored by the American Association for Anatomy (AAA) at anatomy.org. Searchable transcript Captioned audiogram    Flashcards | Stars & Emojis 10.5 minutes Required prerequisites (we want you to succeed) Flashcards: Hidden Powers | Episode 58 More Flashcards: Hidden Powers Unleashed | Episode 59 A star, or other symbol—or even an emoji—can be used to code flashcards by: Star referred to as "five-sided" is a pentagram that can also be described as "five-pointed" ⛥ It doesn't have to be a star. For me, it does—because I still fear being hit by a chalkboard eraser. Importance/priority of study (for test)  Topic or type of flashcards Using symbols can promote the practice of prioritizing learning tasks by prioritizing knowledge, making it a metacognitive habit Is it time to start using the emoji in biomedical literature? | The BMJ (umm, a journal article) my-ap.us/2TbF0cR   Sponsored by ADInstruments (NEW SPONSOR) 4.5 minutes The A&P Professor podcast has a NEW SPONSOR: ADInstruments provides the PowerLab data acquisition systems, Lt online learning platform, and content for laboratory solutions in physiology, anatomy, and biology. They support engaging, hands-on learning with simple set-up and high quality data.

Was ist Stress? Welche Formen von Stress können unterschieden werden? Wie ist das Zusammenspiel zwischen Kognition, Verhalten, Emotion und Physiologie?

Last episode we posed the question: why do our workouts have to be so hard? The scientific answer to this question lies in the concept of the stress-recovery-adaptation cycle, or SRA cycle, derived from Hans Selye's work in the first half of the twentieth century. Simply put, in order to generate an adaptation, which we would recognize as an increase in one or more of the ten general physical skills (strength, endurance, mobility, etc), then you must progressively increase the amount of stress applied during the training program. That is the nature of training: it must become "harder" over time to continue driving progress.   In the 1950's Austro-Hungarian endocrinologist Hans Selye developed a theory known as the general adaptation syndrome which describes the effect of acute stress, generated by a stimulus (real or imagined), on an individual. Selye observed that the effect of stress on an organism was to disrupt homeostasis and, if continued unchecked, eventually kill the organism. If the stress was removed and the organism was given sufficient time and resources to recover from the stress, then it adapted to the stress in a manner specific to the type of stress imposed.   From this work, strength and conditioning coaches have gleaned the concept of the stress-recovery-adaptation (SRA) cycle, which guides the programming decisions behind our training model. Put simply, an athlete wishing to get stronger, faster, or more cardiovascularly fit must be subjected to a workout which stresses her, then recover from that workout by eating and sleeping. When this process is repeated over a period of time, she begins to see results and -- voila! -- she has performed what we call training, or a systematic, planned series of workouts toward a goal.   This is a key observation that we first covered in episodes #1-10 but we must restate now: in order to get stronger (or faster, or more fit, etc.), you must perform exercises which stress your muscles enough to disrupt homeostasis. This is why our workouts inevitably become hard -- they must generate enough stress to drive an adaptation. And this should be obvious; if you keep lifting the same weight every workout, you cannot get stronger. You are already adapted to that weight, thus there is not sufficient stress to disrupt homeostasis. One of the programming variables has to change -- you must do more reps, use more weight, or otherwise increase the volume or intensity of the exercise to drive adaptation. Yet, we see this time after time in the gym. People perform the same exercises, with the same number of sets and reps, with the same weight, over and over again, expecting results but not getting them. In short, these people are merely exercising when they should be training.   At first, just about anything constitutes a stress. For the completely sedentary person, a walk around the block is probably stressful enough to make them both stronger and more fit. This is known as the novice effect, and explains why people get results in the short-term for nearly anything. As Mark Rippetoe, the author of Starting Strength: Basic Barbell Training, is fond of saying, for rank novices "riding a bike will make their bench press go up." Beyond this point, however, a good training program that incrementally increases stress to drive adaptation over a long period of time is needed. Fortunately, novices can make progress nearly every workout for the first few months of their training. In this case the SRA cycle is very short, about 48-72 hours long.   Eventually the novice can no longer add stress to the workout and make progress. This is easiest to observe in barbell training. The novice adds five pounds to the bar each workout, but cannot complete the prescribed number of sets and reps. At this point, he must start adding weight every other workout, and perhaps perform a lighter workout in between, in order to add weight to the bar. Eventually adding weight every other workout becomes every week, then every two weeks, then monthly, and for the advanced athlete nearing their genetic potential for strength, every few months. In these cases, the SRA cycle is stretched over a period of time rather than a single workout.   Though it's beyond the scope of this episode, recovery is equally important. It is, after all, half of the equation. When we recover from a stressful workout our brain makes new neural connections and becomes more efficient at recruiting motor units for the task, our muscles grow, our cells become more efficient at generating ATP and eliminating waste products. Food and sleep are the primary components of recovery. The important thing to keep in mind here is that as you add stress to a training program, the recovery must keep pace, or you risk overtraining and stalling progress, losing progress, and even injury.   Connect with 40fit Radio 40fit website Facebook 40fit Masters Community 40fit Radio on Instagram

Lo que no te mata te hace más fuerte, pero tampoco hace falta fliparse Las duchas de agua fría han demostrado ciertos beneficios en estudios: mejoras en el sistema inmune, mayor quema de grasa, ligera ayuda con la depresión, etc. Aunque si buscamos en Internet encontraremos exageraciones de estos beneficios en estudios hasta otorgarlas propiedades casi mágicas. Creo que sólo me ha faltado leer que si estás calvo y te duchas con agua fría te saldrá pelo. Bromas a parte, hoy no voy a hablar de estudios sino de la aplicación práctica de las duc  has de agua fría. A finales del último verano empecé a ducharme siempre con agua "fría". Si alguna vez has probado lo de ducharte sin darle a la caliente y has aguantado como un campeón o no hayas sido capaz ni de meterte, quizá tu éxito o fracaso tenga mucho que ver con la estación del año en la que te encuentres y por tanto, con la temperatura del agua. Duchas de agua fría: otro estrés positivo Cuando hablamos de las adaptaciones al estrés y al entrenamiento, vimos que la Teoría de Selye nos decía que ante un daño nuestro cuerpo genera una respuesta de recuperación que lo hace un poco más fuerte que antes de sufrir el daño. En este caso el daño, el estrés, tiene un carácter positivo. Puede venir en forma de estrés psicológico, entrenamiento, ayuno o como es el caso que nos ocupa, en forma de ducha de agua fría. Si seguimos con esta lógica podemos cada vez bañarnos en agua más fría hasta ser tan fuertes que podemos pasear en las noches de invierno por los campos de Burgos a 10ºC bajo cero desnudos sin mayor problema. Aunque hay individuos que podrían hacerlo , como Wim Hof (El hombre de hielo), la mayoría de los mortales encontraremos un punto dentro de esta adaptación al estrés en el que el daño, en este caso la temperatura del agua, supere nuestra capacidad de recuperación. No necesitamos llegar a morir por hipotermia o causarnos una lesión, llega un momento en que empezamos a notar que no somos capaces de recuperarnos, ya sea hablando de entrenamientos, de duchas frías o del estrés al que nos refiramos. Aquí tenéis mi experiencia. Experiencia con duchas de agua fría desde verano a finales de diciembre En diciembre la cosa se pone seria. La línea negra discontinua marca la temperatura a la cual ducharme todos los días (con el agua tan fría) se hacía "bola". En verano llevo años duchándome con agua fría, la verdad que es un auténtico placer y realmente no lo considero muy estresante que digamos, más bien al revés. Pero este año me había propuesto incluir las duchas de agua fría también en el invierno. Había leído el libro del Hombre de Hielo y me había motivado bastante, no para bañarme en bolas en enero en un lago helado, pero para al menos ducharme dentro de casa sin darle a la caliente. Otras veces lo había intentado de golpe y me había echado para atrás, pero esta vez estaba decidido. El factor determinante: la temperatura Decir que lo más importante de una ducha de agua fría es la temperatura parece una chorrada, pero debido a las variaciones de temperatura la cosa cambia mucho. Además en pocos sitios encontré la temperatura real a la que se obtenían los supuestos beneficios de ducharse con agua fría. En sólo unos pocos estudios daba una referencia con rangos de temperatura entre los 10 y los 15ºC. Así que para hacerme una idea objetiva de la temperatura a la que me duchaba me compré un termómetro. Es este, está pensado para comida, pero funciona de lujo para medir la temperatura del agua y también me ha venido de lujo para hacer quesos, yogur o cuajada. Voy a separar el asunto en los tres meses que duró el experimento. Octubre La cosa empieza viento en popa. Es un otoño suave y las primeras mediciones de temperatura dan un valor de 24º C. A medida que va bajando la temperatura exterior y nos vamos alejando del verano la temperatura va cayendo, pero me adapto sin problema. La temperatura más baja dentro de casa está ligeramente por debajo de los 20ºC.

Hemos escuchado una y mil veces que lo que no te mata te hace más fuerte. Es una frase demasiado ambigua, así que veamos cómo poder aplicar con algo más de precisión esta máxima, no sólo a nuestro entrenamiento, si no a cualquier estrés al que nos expongamos. Necesitamos darle un poco de caña al cuerpo. El no dársela hará que seamos más propensos a la enfermedad. Evolutivamente está preparado para ello, lo espera. Este daño o estrés (llámalo X) puede ser en forma de entrenamiento, de estrés mental, ayuno, frío, calor... Todos estos estresores bien aplicados y en su justa medida nos benefician y nos hacen más fuertes. Esto puede sonar un tanto motivao pero hay mecanismos fisiológicos que lo explican y está soportado desde hace años por la ciencia. Vamos a explicar bien el concepto y cómo funciona. El concepto de Hormesis Esta palabreja que viene del griego y significa "estimular" es el efecto positivo que tiene sobre nosotros algo que, en principio, es negativo. La clave está en la dosis. Dosis demasiado altas nos causarán un daño excesivo o incluso la muerte, pero dosis demasiado bajas también podrán causarnos daño. Esta última parte no se suele mencionar, pero me parece clave a la hora de entender el concepto y de aplicarlo. Rompiendo el equilibrio La segunda palabra extraña, y última por hoy, es la homeostasis. Es la capacidad de mantenernos estables compensando los cambios a los que nos expone el entorno. Una especie de equilibrio dinámico que busca nuestro cuerpo a pesar de las dificultades. Ejemplo: cuando hago un entrenamiento duro he roto mi equilibrio, he roto mi homeostasis, y mi cuerpo se va a encargar de activar diferentes mecanismos para reestablecerlo. El cuerpo siempre busca recuperar su homeostasis, si le dejamos. Viendo que la dosis puede ser negativa tanto por exceso como por defecto podemos fijar dos umbrales: Umbral de daño superior: estímulo excesivo, rompemos la homeostasis pero nuestro cuerpo no es capaz de recuperarse, sobreentrenamiento, lesión, enfermedad y en casos extremos la muerte. Umbral de daño inferior: estímulo insuficiente, no rompe la homesotasis, nuestro cuerpo no se entera. Como podéis ver en función del daño al que nos queramos exponer tendremos unas consecuencias. La clave está dar el estímulo suficiente para romper la homeostasis, pero sin pasarnos para que podamos recuperarnos. Esto llevado al campo del entrenamiento es la base de la planificación. Exponemos a nuestro cuerpo a una carga de trabajo (daño) y esperamos a que se recupere. En ese momento será capaz de soportar una carga más elevada (será más fuerte, puede soportar y recuperarse de un daño mayor). Luego esas cargas tienen que ir hacia un objetivo concreto, etc, etc, etc. El estrés y el síndrome general de adaptación En el año 1.936 llega Selye con su trabajo: Síndrome general de adaptación, que es algo así como el primer entendimiento de cómo ocurre la adaptación. Algo como la Teoría de la Evolución general de Darwin, pero en una escala de tiempo mucho menor. El Síndrome general de adaptación recoge una serie de estados por los que los organismos vivos pasamos una vez que somos sometidos a un estrés. Descubrió un patrón que se repetía. En el paper Un Síndrome Producido Por Diferentes Agentes Nocivos examinó los cambios producidos en ratas tanto funcionales como estructurales una vez que éstas eran sometidas a diferentes agentes nocivos (bastante nocivos), como daño quirúrgico, frío, intoxicación, drogas y el ejercicio al fallo ("excesivo ejercicio muscular"). Había síntomas que eran independientes del tipo de daño o de droga utilizada. También se repetían estas tres fases: Fase de Alarma: de 6 a 48h después del daño. Expresión de alarma general del organismo ante una situación crítica. Pérdida de tono muscular, bajada de la temperatura y otras más graves en función del daño causado, como perforaciones en el tracto digestivo, necrosis en el hígado, etc.

models of stress as a biological process, with reference to Selye’s General Adaptation Syndrome of alarm reaction (shock/counter shock), resistance and exhaustion, including the ‘fight-flight-freeze’ response and the role of cortisol

Jason Dalton shoots and kills six more people.

  Soul Sunday släpper sitt tredje avsnitt och den här gången så är ämnet relationer. Jag och Sarah har många reflektioner kring ämnet och vi är absolut inga kärleksexperter. Dock så är vi nyfikna på att bli bättre.  Vi lyfter olika böcker och författare på ämnet och ni får en inblick i våra liv. För även om vi jobbar som coacher så har vi inte svaren på alla frågor, utan vi söker ständigt svaren inom oss själva. Och vår förhoppning är attt du som lyssnar börjar att ställa frågor till dig själv, under eller efter podcasten.    Mycket nöje och vi är tillbaka igen nästa söndag :)   Charlott Zsoldos Holistic Health coach http://justlotta.se