Jay Feldman 0:04
Welcome to episode 78 of the energy balance podcast, where we teach you how to live without constant hunger and cravings, fatigue, brain fog, poor sleep and all sorts of other low energy symptoms by maximizing your cellular energy. I'm Jay Feldman. I'm a health coach and independent health researcher, and joining me again today is my good friend Mike Fave. Mike and I have been studying health and nutrition together for a long time now, and Mike also draws on his experiences from working within the healthcare industry. Today's episode is part four of the final part of our series discussing hormesis, and in today's episode, we'll be talking about why maximizing energy production and minimizing stress is optimal for our health. If you're not familiar with hormesis, then I'd recommend checking out parts one through three of this series. But basically, hormesis is a concept that is claimed to be the reason why many things are supposed to be healthy, things like caloric restriction, exercise, various plant compounds, cold thermogenesis, fasting, low carb diets, saunas, supplements like resveratrol and many other popular health interventions, especially in the alternative health sphere. And in today's episode to round out the series, we'll be going over how you can induce mitochondrial biogenesis and uncoupling without inducing stress. We'll be talking about why you want tighter mitochondrial coupling if you want to induce uncoupling in a healthy way. We'll be talking about the difference between reactive oxygen species production in a high energy state versus in a low energy state. We'll be talking about how many supposedly hormetic interventions like exercise, fasting and ketogenic diets can be beneficial despite the stress they cause, rather than because of the stress they cause. We'll also be discussing what the anti hormetic perspective looks like in a practical sense, and how the fact that we can't avoid stress fits into the bioenergetic or anti hormetic view. And that's something that I often hear cited as a counterpoint for this bioenergetic view that we can't avoid stress, but we discuss why that really is not a valid counterpoint. To check out these show notes for today's episode. You can head over to Jay Feldman wellness.com/podcast where you can take a look at the studies and articles and anything else that we discuss throughout today's episode, and if you are dealing with any low energy symptoms, maybe this is something like chronic cravings and hunger, fatigue, joint pain, weight gain, digestive symptoms, brain fog, poor sleep, hormonal imbalances, or any other low energy symptoms or chronic health issues. Maybe this is something like heart disease or diabetes or an autoimmune condition, then head over to Jay Feldman wellness.com/energy where you can sign up for a free energy balance mini course, where I'll explain how these different symptoms and conditions are really caused by lack of energy, and I'll also walk you through the main things that you can do from a diet and lifestyle perspective to maximize your cellular energy and resolve these symptoms and conditions. So to sign up for that free energy balance mini course, head over to Jay Feldman wellness.com/energy, and with that, let's get started.

So we have this opposite situation, more or less, where we do you can create or have the same drive of reactive oxygen species production in a high energy or high ATP state, as opposed to a low one. And in this state, instead of inducing a block somewhere along the electron transport chain and then eventually higher up that forces reactive oxygen species production and oxidative stress. Instead, what we have is in excess of the end product of ATP, and like most chemical reactions, that tends to slow down the earlier parts of the process. And basically what it the way that it does that, is it kind of backs everything up along the electron transport chain, much like a high FADH two to NADH ratio does, although that's only between complex one and two. But so you back everything up where there's less, you basically have a buildup of electrons along the electron transport chain, because you have a lot more ATP and less ADP, ADB, ADP is what uses the energy from the electron transport chain potential, membrane potential, to become ATP. And so when you have a lot of that end product, ATP, of this buildup of electrons along the electron transport chain, that also leads to reactive oxygen species generation, however, and so that. So the important point here is that that will also trigger a lot of the pathways we talked about before, like something like mitochondrial biogenesis and like uncoupling. So the people who are saying, well, uncoupling happens in good situations are not necessarily wrong, because it can happen. You know when, when you do have this high ATP state that leads to reactive oxygen, oxygen species production. You. Again, same thing with building more mitochondria, right? It entirely makes sense to have signals to build more mitochondria when basically, you've capped off the like, you've topped off the amount of energy that could be produced in any individual one, you've become so efficient and so effective at producing energy, and you've got extra substrate, substrate, so then that's a perfect signal to create more mitochondria and be able to produce more energy as as a whole, as the organism, and use more substrate, and basically up regulate your metabolism. So that's that is the kind of larger context of the high energy state. But there, there are a couple of really important differences here that work on the biochemical level to to do a couple things, but one of the most important ones is protecting against the oxidative stress. And so basically, because we have the elevated ATP, and also elevated CO two which comes along with that proper glucose oxidation that leads to high ATP, those two things are very, very protective against the reactive oxygen species. Help to keep them to a minimum, just enough to kind of trigger those things and also protect the actual cellular structure from those and without the need of driving all those antioxidant pathways to the same extent, and kind of without the need of driving all the stress pathways and all the depletion that comes with those things.

Mike 6:18
Yeah, I mean, it's and you see if you look even if you look in the Wikipedia page. But essentially the other things that increase uncoupling or increase heat generation are also over overfeeding. And you see changes in hormone profiles like including thyroid hormone with overfeeding. So while you can degenerate in a kind of adaptive way downward, you can also regenerate in an adaptive way upward as well, so it can go in in either direction. And the difference is whether the cell is registering energy or not. And that's really the I think that's the ultimate like the key point here, the other thing I wanted to touch on really quick was that a lot of the people who are making these arguments for hormesis are all looking at proxy values. So it's like, oh, NADH to NAD ratio. And you can, you can get a sense of how they're thinking about things because of the things that they recommend. It's like, oh, I'm going to adjust my NAD to NAD treat NADH ratio because, so I'm going to go get infusions of nicotinamide riboside, and it's like, Yes, that'll increase your NAD to NADH ratio. But the NAD to NADH ratio is a proxy for how much energy you're producing, to some extent, and it's the reason it's a proxy value is because it's basically, if you have higher NAD, you're essentially a it means that you're running those electrons that are stored in the NADH through the electron transport chain, and now you have the NAD carrier to come back and pick up two more pick up a couple more electrons to become NADH. So it's, there's like, there's, that's the difference in interpretation, and I think that that becomes really important. And that's why you have people recommending these things. It's like, oh, it increases on it, just like this general idea, oh, it increases on coupling. It's like, but how and why is it? Why isn't coupling being increased? Is it being increased because you have so much energy being produced at the cell that your body's like, oh, we can turn some of this into heat. Well, that's excellent. You the heat maintaining body temperature at a higher set points, or at certain set points, is extremely beneficial. Obviously, fevers are, you know, that's a different story. Um, so, yeah, it just just, it's important to understand why, and it's important to look at the argument that the individual is making as to how it's generating it like you don't want to, like it's making the argument, oh, I'm going to increase NRF two by inducing my fatty liver. So I'm just going to have a whole bunch of endotoxin at the gut causing the liver to accumulate fat, and then and then have ROS generation and upregulate NRF two. It's like, that's not how you would want to increase NRF two. But NRF two is increased in that state, which doesn't make it a good thing, but it also doesn't make it a bad thing. I mean, there's a reason that it's increasing, and it's increasing to deal with the excess ROS that's being produced at the mitochondria. So like, the adaptive pathways are there, and they're important, and it's not saying to not have them, but the question is, is, why are you activating any of these adaptive pathways, and what exactly are you adapting to, right? Are you adapting to being in a higher energy state, having adequate energy ATP production, et cetera, and then uncoupling? Or are you uncoupling because your electron transport chain is all messed up and you're producing too much Ros? Well, those are two very different scenarios.

Jay Feldman 9:37
Yeah, yeah, absolutely, absolutely. And to I want to add some support and distinction for those two scenarios and how protective and how much of a difference it makes to be having oxidative stress, or not even oxidative stress, to be having reactive oxygen species in the presence of high levels of ATP and CO two, as opposed to in the presence of low levels of those things. And the. Difference that that has on the oxidative stress, on the effect of those reactive oxygen species. Because a lot of people talk about how important and necessary reactive oxygen species are as signaling molecules, and that's true, right? They signal all these pathways that have a lot, potentially a lot of value, depending on the context, but that doesn't mean they have to be causing damage and stress at the same time. So there's a great study looking at this, and they're looking at it in the retinal cells, the retinal pigment, empathy, epithelial, epithelial cells in the eye. And just reference. So they're gonna, in this quote, they use that acronym, RPE, just so you are familiar with what, what that means. And so in the study they were, they basically looked at low levels of ATP versus higher levels of ATP and what happened when they were when they were reactive for oxygen species introduced. And so they say that attractilocide treatment reduced cellular ATP levels by 30% mimicking the energy status of aged RPE, TERT, butyl, hydroperoxide, decreased reduced glutathione and RPE cells with lowered ATP levels, whereas cells with normal ATP content were not affected. So just to start in this, this first part, basically they tested out using a substance that decreases ATP levels. They did it to a point that it depleted ATP by about 30% which mimics what they saw in aged cells. And they stated that in the situation where there was that decreased levels of level of ATP, there was less reduced glutathione. And then they'll go on to talk about oxidative stress. So they say that the TERT butyl hydroxo, hydroperoxide, which I'm just going to say, is tbh. So the tbh induced oxidative stress resulted in substantial accumulation of Malindi aldehyde protein adducts in cells with lowered ATP, while cells with regular ATP levels were only modestly affected. So here they're talking about normally, it's the acronym is NDA, but it's Malindi aldehyde, which is a lipid peroxide like damaged, often polyunsaturated fats, yeah, which happened, which are basically a marker of oxidative stress. And so they found that there was increased levels of those and increased accumulation of those in cells with lowered ATP compared to regular ATP. Then they also say that the tbh induce more oxidative DNA damage in cells with lowered ATP levels than in cells with regular ATP. And then they state that in the treated cells, the ones that are treated with the attractilocide that depletes ATP, autophagy rates decreased to threefold as compared with controls. Phagocytic capacity for uptake and degradation of photoreceptor segments was reduced in RPE with low ATP. So that last part, which is something that we talked about before, is that even the ability to properly adapt to a, quote, hormetic stimulus of oxidative stress, when there's lower ATP available, is reduced. The ability to adapt is reduced. So the ability to even induce autophagy was decreased. In this case, they say threefold. So again, this is part of the problem with as you described, when you're just looking at these certain pathways, and you're saying, Oh, well, autophagy is induced by these oxidative stress pathways and all the intermediates along there, so we just want to increase those. But when you do that in the context of the depletion of ATP, you're not even going to be getting the autophagy that you want because of the lack of energy. And they concluded this, this part, or their their paper, by saying that moderately decreased ATP levels, such as seen in aged individuals, might contribute to the vulnerability of RPE to oxidative stress, damage and to dysfunction. So I think that kind of summarizes it nicely.

Mike 13:37
Well. I think what you see here is that you have, not only do you have, you had increase with decreased ATP, you had increased cellular damage, but you had decreased capacity to clean up that cellular damage, whereas, when you had the adequate ATP, you had less cellular damage, and you had the capacity three full times capacity to clean up that that cellular damage. So the other thing too is, why is? Why is the autophagy even being stimulated here? Right? Because of the cellular damage. So it's like, you also need to be careful on what, what's causing autophagy and what's not. And we saw that in fatty liver as well, where autophagy could not, the couldn't be performed by the cells that were basically the fat overloaded cells. Or, I think that was in the statosis state, where there's inflammation, autophagy had been eliminated because there wasn't enough there wasn't adequate energy to support it. So you have now, then that's where you're starting to see the adaptive systems break, where you having more damage than the cell can basically repair or clean up. And then, obviously, over time, that's just a losing battle. Yeah. And so you're seeing the same thing with the retinal pigment cells here, with ATP depletion,

Jay Feldman 14:45
Right, right, exactly. Yeah. And, and not only is it a losing battle, it's a battle that it's it is a stimulus that is furthering down that chain, furthering down that, that inability to to adapt

Mike 14:57
Yeah. So essentially, over time. Time, it's because a lot of people like to compare the body to a machine, but the body's not a machine. And the key difference, I think, you know, at least for this conversation, is that there's the ability of, of like, consistent internal renewal, where the the body is capable of constantly renewing itself, whereas for like, the thing, the machines that we produce don't really renew themselves. It's literally like replacement parts type of deal. And so what you're seeing in these these degenerative processes, is a destruction progressively of the ability to renew itself, to renew the self. And then essentially, you get to a point where it's like that renewals. It's just not going on here. So you're just then you just start getting insult after insult after insult.

Jay Feldman 15:47
Yeah, there's literally just not enough energy there, there to support the structure. And you, you start to generate, yeah, instead of regenerate.

Mike 15:55
Exactly, which is why Ray's hypothesis, energy and structure are interdependent at every level is so powerful and makes so much sense, especially when you start going through the research, and you start looking at how these things are developing. Without the energy, you lose the structure, and then, yeah, subsequently you with you continually lose the structure. When you see with cancer, you also lose the ability to generate that energy. And when that, when that happens, then we're at a severe deranged, like, that's a very severe derangement in the system.

Jay Feldman 16:23
Yeah, and even not in cancer, just in aging, right? I mean, the, and this is, we talked about this in that aging series, that the that, the, you know, one of the things that correlates with energy is lower or, sorry, that correlates with aging is lower energy availability. And, for example, in this, you know, study, they were looking at those aged cells, and they were literally, they literally just took cells from people who were over 60 years old and saw that they typically had about 30% less ATP available.

Mike 16:48
So, yeah, it's you're seeing, and that's not because, as you said, it's not because you aged. It's like, that is the cause of the aging, is the inability to produce the ATP that is aging, yeah, exactly, exactly. That literally is aging. Is the the progressive loss of ability to to produce energy with which goes hand in hand with the decreased structure. Yeah, yep, yep, exactly. And so the one last piece here, the goal is to not increase that process. The goal is to not add stress into the system to increase that process for some supposed adaptive mechanism, right? Like, the goal is to not have to like force the adaptive mechanism. The goal is to force like a kind of, like an anabolic type of state, rather than like a catabolic, adaptive constant, adaptive type of state.

Jay Feldman 17:45
Yeah and yeah and so to go on a little bit more about the availability of energy, being able to protect, protect the cellular structure and the and protect against oxidative stress, we have another study that was also looking at what goes on with basically the capacity of aged cells. And so they state that the results showed that levels of oxidative lead modified proteins increased with age, not only in whole cell lysates, but also in mitochondrial fractions, and this change correlates with a decline in the intracellular ATP level, younger, meaning less than 60 years old, cells were more resistant to necrosis induced by hydrogen peroxide than were older cells, which are older than 60 years old, which contained lower levels of free ATP than did the younger cells. Treatment of all treatment of cells of all ages with inhibitors of ATP synthesis made them more susceptible to cell death, but also led to a switch in the death mode, from apoptosis to necrosis. And so that's from a more organized cell death to a less organized cell death. They then state. Furthermore, hydrogen peroxide treatment led to a greater accumulation of several inflammatory cytokines, various interleukins, and increased necrosis in older cells. These results suggest that age related decline in the ATP level reduces the capacity to induce apoptosis and propo promotes necrotic inflammation. This switch may trigger a number of age dependent disorders. Again, we're just saying that that exact situation here where low energy, low ATP plus reactive oxygen species is very different from high ATP and reactive oxygen species, and when those things are decoupled, when you have low ATP and high reactive oxygen species, you end up with a lot of oxidative stress, a lot of damage and aging, essentially. And then all of what they describe as age dependent disorders, all the age dependent disorders, which are just all of the chronic health issues that happen to be happening in people who are younger and young, younger nowadays. So maybe they could just take people who are over than, like, 30, older than 30 years old, and use their cells instead of 60.

Mike 19:49
Yeah, and this goes this, all of this goes hand in hand with a lot of the other things that we talk about as well. Specifically, as far as, like, having a cell structure that's not. Super unsaturated, because you're essentially it's one way to protect yourself from ROS and what, and basically allow the structure to be, could be solid, be maintained. Well, it's having adequate protein intakes, having added, you know, eating less polyunsaturated fats, all of these pieces, and then minimizing endotoxin from the gut, whatnot. All these pieces are ways to not only minimize that ROS and energy depletion, but at the same time maintain a like a solid structure so that you can produce energy. And that's one of the protective mechanisms of the lower polyunsaturated fat there, because they're the most likely to be targeted by Ros, particularly at the mitochondria and the and the cell.

Jay Feldman 20:41
Yeah, and beyond, being more likely to be targeted, so leaving you more susceptible to oxidative stress, they also reduce the efficiency of energy production. So they, on their own, will decrease or, well, they'll decrease the ATP to Ross ratio, or increase the Ross to ATP ratio, because they work to reduce that efficiency along the electron transport chain as well, much like a lot of these other interventions. And interestingly, of course, a lot of people in favor of hormesis are not in favor of omega six consumption in the form of vegetable oils. Yet Omega sixes are are pretty effectively hormetic.

Mike 21:13
So yeah, well, then, but they are in favor of Omega three, which can arguably be worse which. And I think we talked about that earlier with the the caloric restriction study, with the omega three fatty acids actually having worse outcomes because of what it was doing at the mitochondria and lipid peroxidation, and then, and then. The other thing here that is also to adjust this is that also goes hand in hand with this, is that oxidizing more carbohydrate, or largely carbohydrate, also helps to fix that ROX production, as we talked about earlier, with the fatty acid versus fatty acid oxidation, which I think leads us into our next point here. So I'll let you, I'll let you dig into another protective factor besides ATP.

Jay Feldman 21:58
Right, Yeah, so that next one, which I'd mentioned, is carbon dioxide, and as you're talking about, we produce 50% more carbon dioxide from carbon dioxide, or from carbohydrate oxidation, than fat oxidation, and that's if they're happening at the same rate. Normally, carbohydrate oxidation functions at a much faster rate. So probably, honestly, we're getting, you know, couple 100% more...

Mike 22:20
Per unit time, right?

Jay Feldman 22:22
Yeah, per unit time

Mike 22:23
The difference is per unit time.

Jay Feldman 22:25
yeah, as opposed to per run through the through respiration, yeah, with every two acetyl CoA, or, you know how, whatever constant you want to use. So, yeah. So carbon that carbon dioxide production, which is associated with the higher metabolism and the higher rates of glucose oxidation, which is the opposite of all those degenerative states with all the fat oxidation like like cancer, as we discussed, that carbon dioxide is extremely protective against oxidative stress and also helps to encourage coupling, which helps to increase the efficiency of ATP generation compared to rust production, which then helps to induce uncoupling faster. We'll come back to that in a second, because it's an interesting dichotomy that I think people miss a lot. So when it comes to carbon dioxide, this first study, and these are two studies that are both by the same researchers, but they've got a couple of good quotes, and the first one, they state that finally, it was established that CO two led to the better coordination of oxidation and phosphorylation and increase the phosphorylation velocity in liver mitochondria. So they're talking about carbon dioxide, basically increasing the rate of respiration, increasing energy production. And they say that the results clearly confirmed the general property of CO two to inhibit significantly the active oxygen form generation, which is ROS generation, reactive oxygen species generation in all cell types. And then in their next study, they state that the results obtained suggest that CO two at attention, close to that observed in the blood and high tensions, is a potent inhibitor of generation of the active oxygen forms by the cells and mitochondria of the human and tissues. So what they're pointing out here is that not only does this happen when you're just looking at cell culture or whatever, but this happens in the levels of CO two that you can produce if you're running a good metabolism and a lot of glucose oxidation, and being able to retain that CO two well, and not one half breathing, not in doing it off hypoxia, yeah, and hypocapnia.

Mike 24:20
The other thing too is that the we've talked about this before, and which is very basic mechanism, but the Bohr and the Haldane effects directly show that the CO two will enhance oxidative phosphorylation as well, by allowing oxygen to unload to the cell and become the final electron acceptor in the electron transport chain. And then in thinking Gilbert Ling's hypothesis, CO two interact with proteins. And I think Dr peat has talked about this, where the CO two interaction of proteins has a stabilizing effect on the structure as well. So generating, so it's not so this, I just want to put this out here. It's a little bit tangential, but heat generation and CO two production. Are not waste products. They're like their heat generation is entirely essential for all of the enzymatic and metabolic activity inside the body. The cells are literally attempting to maintain a regular state of body temperature to function appropriately. And then CO two is intimately involved with energy production, so this is just more reasons to not upregulate uncoupling protein in energy deficits, but to still have it up regulate with adequate energy production, and then to oxidize carbohydrate over fatty acids, because not only do you produce less ROS but you also produce more CO two. And what we were talking about earlier was you produce more energy per unit time and more CO two per unit time than the fatty acid oxidation with less ROS.

Jay Feldman 25:55
Yeah, that's Yeah, yeah. We talked about that in the those nutrition with Judy episodes comparing glucose oxidation, fat oxidation, and how much faster glucose oxidation works and more efficient, less reactive oxygen species production. That's why our fat, or fat our brain, does not use fatty acids as a fuel. We talked about that in other episodes too. I'll link to those, but yeah, it's it's hugely important, and we talked through those details as well of how beneficial carbon dioxide is and how it helps to drive more efficient respiration, both as far as how you actually respire with air, but also how your cells respire to produce energy. And it brings us to another point that I said I wanted to circle back to, which is a somewhat counterintuitive idea, which is that the tighter coupling of respiration of the electron transport chain and the Krebs cycle is better for inducing uncoupling, and makes it easier to induce uncoupling in a healthy way than less efficient respiration and less efficient coupling in the first place. And so we were kind of talking about this with polyunsaturated fats, where basically they're worse at producing a lot of ATP per reactive oxygen species, but if you're functioning really efficiently and producing a ton of ATP and much less reactive oxygen species, and doing a much better job of topping off those ATP stores, that's going to lead to then the production of more reactive oxygen species in the shift into the high energy kind of adaptive state that we've been discussing much faster than if you're running at, you know, 80% efficiency or whatever, and producing less ATP, and you're kind of stuck in that middle zone while also getting all of the oxidative stress, because you've got, for example, if you have a lot of PUFA around, or if you just don't have the ATP and CO two available to protect against that. So yeah, just a little potential kind of side note there. But I think I don't know if there's anything else you want to add in terms of of the ATP and CO two being protective. But I think as a whole, what we're getting at here, and what we're showing is that when you adapt to a low energy, high stress state, you and we talked about this recent you know, before you get better at resisting or tolerating, I should say that stress, but it comes at the cost of that complexity. It causes aging. It leads to these degenerative states, and then you have the opposite and opposite state and the high energy still Ross producing state, but that is what allows for signals that allow for an adaptation to again, create more energy, create greater complexity and regenerate, as we were talking about regenerating and fixing those broken links, or those weaker Links, potentially even for future generations.

Mike 28:41
Yeah, yeah. I there's not. I don't have too much more to add to that. I mean, I guess the the idea here, if you if we're taking raise hypothesis, is to maximize the structure and then also maximize energy production. And so all the things that we talk about dietary and lifestyle wise and supplement wise, and all that are all basically through that lens, which is antithetical, and we're basically built, we're basically trying. We're taking down the hormetic arguments piece by piece here, and then showing providing alternative perspective for those hermetic arguments in like a broader context. Besides just, oh, this does this to certs, and this does that to AMPK, and this does that to, you know, whatever else autophagy like, instead of just throwing around big, fancy words and like trying to list all the things that do XYZ to what it's like, putting it into a larger context with which to view everything through, and then the so it's like that that context comes from more of like a Cellier approach of looking at, you know, looking at stress through looking at stress as a whole, and looking at stress through the idea of an allostatic load, rather than this weird kind. Of productionistic, hormetic ideas, which are not also non quantifiable a lot of times, which you talked about earlier. So, yeah, that's it's just optimizing that energy flow, and that energy production, which is still all comes down to, you know, oxidizing carbohydrates, not as much fatty acid. And then also optimizing the structure, which includes lower fine saturated fatty acid consumption, adequate protein in the diet. And then, just to bring this into like, a real world perspective, just what does this actually look like in real life? As far as like, what you're talking about with when you apply excess stress to system, you have loss of XYZ. You are, I guess we'll get to that in a little bit. I won't, yeah, I don't want to jump ahead too much.

Jay Feldman 30:48
Yeah, we're just about there one thing you said you were talking about just taking race hypothesis. And I just wanted to clarify also, you're not saying that you're, we're that these ideas are just based on some blind belief in something that Ray Pete has said, but rather, we've described like we have throughout the last 70 plus episodes, talked about this hypothesis in the context of various disease states and health states and everything and inputs, nutrition, everything, and it lines up perfectly. We're not just, it's not just something. We're taking it, you know, blindly.

Mike 31:21
I think Ray..

Jay Feldman 31:23
It's just a good summary. Is a good way to summarize what like, I know you come back to that hypothesis because it is good some like summary of the larger picture, not because we're just taking it because it sounds nice.

Mike 31:35
Well, I think I, if I had to guess, I would guess that Ray spent a lot of time reading and looking through things, and then basically form the hypothesis. Because it just be as you look at things, and perhaps it's my confirmation bias, but it just constantly shows itself, like as you continually go through everything, and you look at look at things like this lens just continually. Is like confirming itself, confirming itself, confirming itself. And it's, it's overarching. It's not just like this, like the hormetic approach is super reductionistic. Like the overarching premise becomes reductionistic. And it because it's like, you need to find the right dose of this, supposed like, the right dose of everything in every particular situation, which it just, it's like trying to, it's like, when the same approach, the same perspective or concept or thought way of thinking as like, let's just find all the genes and then see what like all the genes code. And it's like, Oh, we found all the genes, and then it's like, oh, well, that didn't really tell us much. And it's like, most of these things aren't even gene or don't even code anything like it. The hormetic approach, like, goes in that same vein of thinking, and it doesn't make any sense. It's just it becomes like, let's like, create this massive database of all these possible combinations for everything. Whereas Ray's hypothesis is like, when you go through and you start looking through the research and you look at it, it's like, it's so simple, but it also just, it just seems to make sense in all these different circumstances. And that's why, you know, the preference for us and is, or at least for me, it was like this hypothesis. It just makes sense, and it's so simple, and it covers things in such a broad way. It doesn't mean that other things don't come into play. But you're seeing this in, like, every single disease, state, loss of energy, loss of structure, loss of structure, decreased energy production.

Jay Feldman 33:26
Yep, yeah, absolutely. And so taking that into this kind of anti hormetic view, we talked about what that can look like physiologically, in terms of, specifically, respiration and energy production and structure, and how those things are all interrelated and and the difference between the high energy and low energy state. And so I want to break down a few of the the factors that are considered to be hermetic and how they can be beneficial despite stress, rather than because of the stress they cause, and some evidence that these things are not beneficial because they're causing stress, but are rather beneficial for other reasons, and just kind of to further support that hormesis is not a viable explanation for what's going on here.

Mike 34:08
So these are specific effects, correct?

Jay Feldman 34:10
Exactly, yeah. So we touch on this a little bit in terms of some of the beneficial specific effects from some of these things. So to touch first on exercise, which is one of the main the main things decided to be hormetic, if, if any of these and just to to, I guess, create the the lens. If these things were hermetic, we would have to be able to confidently say that the stress that they induce is responsible for their benefits, as opposed to something else being responsible for their benefits. And so there's several reasons why, when we look at something like exercise, something like exercise, it does not seem to make any sense that the stress would be responsible for the benefits. And so the first thing that we would that I think is worth touching on here, is looking at sedentarism versus light activity, very leisurely activity, and how these how. Important these things are relative to physical activity and intense physical activity. And so the first thing is that being sedentary is universally shown to be very harmful, and very small shifts into very light activity are shown to be very strongly reverse, like are able to strongly reverse those effects. So these are things that would not be stressful at all, just moving around the house, activities of daily living, being on your feet, as opposed to, you know, literally being sedentary. And so those things are going to be very beneficial, but are not really stress inducing. And the amount of energy that they would require their stressor effect would be very, very small relative to their benefits. But then the other piece that we see here is that sedentarism, being sedentary is extremely harmful, even if somebody is physically active for a period of time every day. So for the person who is sedentary all day, but then works out intensely for an hour, that is still harmful, that being sedentary is still harmful, and even just breaking up the activity throughout the day is beneficial. And so if you think about it, breaking up the activity throughout the day would be much less stressful, much less stress inducing. And at the same time being sedentary, the fact that being like that, having the intense physical activity is not able to make up for the set in tourism. Is also a suggestion here. The suggestion here that the stress from exercise can't be or is not what's responsible for the benefits. And instead, there are other aspects of the movement, and especially having that movement throughout the day, and not being still or seated for, you know, extended periods of time throughout the day is like is the difference? You know, having that mobility is the difference being, being having movement is the difference, as opposed to causing stress. Do you want to add anything there?

Mike 36:53
Well, it just destroys the hormetic idea of like you need to induce this massive stress to to have a benefit from exercise. And I think that there's, like, there's been, there's studies showing that increased rest periods in resistance training decreased stress hormones. Having some carbohydrate during resistance training decreases stress hormones. Just having the taste of something sweet decreases stress hormones. And then obviously there's also the idea, even within the resistance training world, that you're only your exercise, or your workouts are only as good as what you can recover from. So there's a lot of research basically looking at saying, Okay, this X amount of volume is kind of where you should be at, where you're getting and it's essentially what they're really saying, or at least from my perspective, and I think we're going to cover this, but this is the amount of volume that gives you that hyper hypertrophic effect, that gives you that anabolic effect without causing too much stress. So it's about finding that minimum effective dose, and that's what that's essentially where things going. And that's a specific effect, rather than a stress effect, because you're looking for the anabolic effect, not necessarily the stress so, and I guess the argument is like, oh, perhaps it's you need the anabolic effect comes through stress. But I think it's come into question recently. The idea that muscular damage has is actually the cause of muscle growth. I don't think it's not actually muscular damage. It seems to be more like time under tension. So the tension applied to the muscle and the load in the neural activation less, so the actual like damage to the muscle tissue. I don't know if you want to...

Jay Feldman 38:36
Yeah, yeah. There's, there's a lot of great newer research looking at that. And they're they look at mechanical loading versus the amount of stress and the amount of damage caused. And yes, the way that that can look is like considering excess amounts of volume versus lower volume, maybe higher intensity. But basically, what they're finding is that the mechanical loading is more responsible for what they call myofibrillar hypertrophy, as opposed to the damage and stress creating sarcolemma hypertrophy. And so there is some, in other words, there's some growth in the muscle in both situations. But what they're finding is that the there's a difference in what's actually going on with the protein hypertrophy, like the different types. And basically, in the sarcolemmal form, you become better at handling a lot of volume, and in the myofibrillar form, you become stronger. You become better in terms of taking on the mechanical tension and mechanical loading, which again, comes back to those specific effects and how, I guess, another way of saying it is you can have the myofibril or hypertrophy without the stress. It's independent of the stress and or even despite the stress, and tends to also be responsible for greater amounts of hypertrophy as well compared to the sarcolemma. So that's Yeah, another piece here showing that even within the exercise that you are doing, again, it's it is effects outside of the stress that are, yeah, the specific effects that are responsible for the benefits and not the stressor effects. And then another one, like another i. Way to look at the exercise is by looking at isocaloric exercise, where you have two different types of workouts, for example, like a low, steady state cardio versus, you know, sprints for a short period of time. And they'll take, uh, isocal, you know, they'll do an isocalic study. So both sides are using the same amount of energy, they have the same stressor effect, yet they end up with different results. So they just find different performance in terms of or different effects in terms of strength, or effects on fat loss, things like that, again, independent of the stressor effect. And these are just unique to, in this case, something more like the mechanical loading, the type of mechanical loading, as opposed to, as opposed to the stressor effect. And if anything, normally, the the long steady state cardio is has a greater actual stress from from its stressor effect.

Mike 40:48
Yeah, well, the long, the long distance cardio, too, has been known to cause heart problems and to cause energy changes industry in the vascu, yeah, and to cause, like, the marathon type of things, causing, like, like, severe inflammatory states, and then, like, damage the gut barrier, and then chronically doing that, also causing issues with the heart. So it's just like, that is, that's the stressor effect.

Jay Feldman 41:14
Right, right. And so people in favor of hormesis might say, Oh, well, they just went too far past the hormetic zone, right? But these are, like, in these studies, where they're looking at isocaloric, meaning that should be the same amount of stress for the most part in each case, at least the same stress or effect in each case, there's still differences in effect.

Mike 41:33
Yeah, and you can, you can see it too. You can see the differences in the different type of athletes. And I know everyone's talked like it's kind of like a meme, I guess, at this point, but like a distance runner versus a sprinter versus a power lifter, the power lifter, the Sprinter, the body builder, the I don't know any other type of trap, any other type of like short burst or strength based athlete is going to have a much better body composition and physical appearance. And I would, I would bet money health than the distance runners. Most of the distance runners essentially just look kjex So or like waste. Their bodies have been wasted. And then you also, in the studies, also show damage to their hearts from from long, long distance, long distance of running on a regular basis, like the stress becomes overwhelming.

Jay Feldman 42:23
Yeah, yeah, yeah, you see that in cycling sometimes even more. So yeah. Running joke that we've heard here was people talking about that, but anyway.

Mike 42:35
what that cycling?

Jay Feldman 42:37
just that, like, there's a lot of cyclists that don't look like they're cyclists. Don't look like they're athletes. Don't look like they fit.

Mike 42:44
You see, you do see that all like, I haven't seen it in Amarillo, but where I was in, uh, in Florida, like, there's, like, a lot of people who like to cycle, and it's usually like, older, older guys, and they're just like, you know, they're they like, wear their little tight suits. And it does. They're not in good shape at all, but they're like, biking miles day. It's like, I don't know, at least from and then you go to the to the to the gym with, like, bodybuilding, powerlifting. It's like, I don't, don't do a single ounce of cardio ever, but just like, in great shape, like, and I think a lot of people come, like, come to, like, consult about that too. It's like, Oh, I did all this cardio, I did all this weight loss stuff, but I still don't see my abs, because I get that question a lot. I don't know, a little tangential here, but it that's because you've taken fat off, or you've lost body weight, but you haven't, you've moved into a stress state, and you haven't adjusted the hormonal profile. And the hormonal profile is really what's going to allow you to see your abs, have your muscles look a certain way, and have your body composition be a certain way. And you're not going to get that through just stressing the crap out of yourself. You're going to get that through the specific effects, not the stress effects, the specific effects of eating the right way, sleeping the right way, working out the right way. And that's there's huge differences there. And I think that's what that's where you see like the hormetic approach, or like the calories in, calories out approach, just not making any sense, and people not getting outcomes they want because the perspective is wrong.

Jay Feldman 44:14
Yeah, yeah. And just to add in as well, we're not saying that necessarily, all the people that you find in the gym, even if they have good physiques, that they're healthy either, there can obviously be a ton of issues with that whole industry and the way that health is looked at in those terms. And yeah.

Mike 44:30
Well, they they're but I think they're the people that are looking like amazing even though they're like kind of in bad health, like what they're doing a lot of times, which usually includes anabolic steroids, is indicative of what we're talking about here with where you want the specific effect, rather than the stress effect. So they're like, doing all these things to stress the crap out of themselves, but they're essentially using an anabolic steroid which would give them that specific effect to look a certain way. So. So you're not, and I'm not. I'm not condoning it, but what I'm saying is it's just more evidence for the idea of the specific effect of the exercise, for the hormonal profile. And they're essentially doing it exogenously, not through exercise to, like, look and be and feel certain way. It comes from that hormonal profile effect, the specific effect, and not this, like stress effect this, yeah, yeah.

Jay Feldman 45:26
There are also those antibiotics. There is also help reduce the amount of stress from those stressors as well, so that it helps on the recovery side a lot, which is another huge piece there is that they're getting less stress even from the same stressor. And we'll talk about how you can do that in other ways as well, which is perhaps a better approach, but as you're saying, kind of indicative of like that. That is kind of a representation, potentially, of of that state. Another thing I want to say as well talking about cycling is I had a neighbor who was a cycler and had a heart attack, he lived. But just everyone was very surprised, because he was no, you know, they always saw going out.

Mike 46:06
Well, you hear that all the time, right? You hear that. It's like, oh, so and so, like, they put, they ran all the time, or they were a vegan, and they had a heart, and it's like, and then they had a heart attack. It's like, well, yeah, yeah.

Jay Feldman 46:16
Wasn't even high. It was, you know, 180 150.

Mike 46:22
There's a lot of studies showing that most people with heart attacks don't actually have super high cholesterol. I'm pretty sure.

Jay Feldman 46:27
Yeah, I think it's like just half, about half people have heart attacks don't have high cholesterol.

Mike 46:31
Yeah, it's and again, that's again, it's the perspectives there are the problem. When you look at the research, it makes sense. Yeah, you know, if you're, if you're vegan, you're eating tons of oils, like, Okay, you got a heart attack, okay? Makes sense. Or, like, if you're gonna run high amounts of exercise and then you're gonna have a heart attack, like, like, endurance training and whatnot, you'd be like, Yeah, that makes sense. You did it to yourself. But the mainstream narratives, which I think hormesis moves into this because of the way, because of the narrative itself. It just is like, becomes paradoxical. It's like, there's really no paradox there.

Jay Feldman 47:05
Right, right.So, so moving on to some, to another comparison of some of those stressor versus specific effects in terms of probably the most popular interventions for hormesis being low carb ketogenic diets and fasting. There's a couple of good studies looking specifically at the role of the gut in in these in these states, and how the gut, the just the role of the gut alone, can be responsible for the effects. And of course, if that's the case, then it would have nothing to do with this stress induced and we talked about this before in terms of calorie restriction, the many things there that are responsible for the benefits of calorie restriction, that are not the calorie restriction itself and are not the stress itself. But again, you see the same thing here when it comes to things like fasting, ketogenic and low carb diets. And so I've got a quote here discussing fasting, where they talk about how an extended fasting period, ie gut rest, could also lead to reduced gut permeability, and as a result, to blunted postprandial endotoxemia and to blunted systemic inflammation, which are typically elevated in obesity. So again, here in the study, they're pointing out that one of the main things responsible for the benefits of fasting is reduced gut permeability, less endotoxin, and therefore less inflammation. And of course, that that conglomeration of symptoms or factors is seen in obesity, and then to and then the following one talking about ketogenic diets, where they basically describe here how the gut is responsible for mediating the benefits of ketogenic diets, specifically, the anti seizure effects, is what they're looking at here in epilepsy. Yep. And so what they point out is, or what they say is, that here we show that the gut microbiota is altered by the ketogenic diet and required for protection against acute, electrically induced seizures and spontaneous tonic clonic seizures and two moss mouse models, mice treated with antibiotics or rare germ free are resistant to ketogenic diet mediated seizure protection. Enrichment of and Gnotobiotic co colonization with ketogenic diet associated akermansia and parabacterioids restores seizure protection. Moreover, transplantation of the ketogenic diet gut microbiota and treatment with akermansia and the parabacterioids each confer seizure protection to mice fed a control diet. And then the last thing that they state is that alterations in colonic luminal serum and hippocampal metabolomic profiles correlate with seizure protection, including reductions in systemic gamma glutamylated amino acids and elevated hippocampal GABA to glutamate levels overall, this study reveals that the gut microbiota modulates host metabolism and seizure susceptibility in mice that was quite a quote haha.

Mike 49:58
That word that was a that was a word salad. That's just the all the largest words that we could find in the medical dictionary. We're just gonna put it in our in our papers, so that everybody thinks that we're really smart.

Jay Feldman 50:13
I hope some of that came across like, I hope like the meaning of what was written came across through the the jargon.

Mike 50:19
It was essentially that the that the mice, the no to biotic mice, so the mice that don't have any that are germ free mice, essentially were like they didn't get the protection from seizures with the ketogenic diet, alteration in the microbiome. And then what they're saying was, I guess, the acromancy on parabacterioids, where the bacteria responsible for the benefits seen in the ketogenic diets protecting against epilepsy. So based and basically, if they removed the bacteria, bacterial changes in microbiome, they didn't see the benefits in the ketogenic diet anymore, which essentially eliminates the explanation of the ketones being these, like preferred fuels for the brain, and this and that, and which the ketones being the preferred fuel for the brain, still doesn't explain a hormetic perspective, either, right? Because you don't have to, like, you don't need to be in that hormetic state to reduce the ketones, per se.

Jay Feldman 51:17
Well, you need to be under stress to produce the ketones.

Mike 51:20
Can you use MCT oil, though, couldn't you use MCTs?

Jay Feldman 51:23
Yeah, so unles you're taking something exogenously, that's going to lead directly to ketone production. So, so I guess I'd say in a ketogenic diet, there's definitely stress, like stress induction of ketones. But if you were to, as you're saying, if you were to just introduce the ketones without the ketogenic diet, and use the ketones for for the brain there, then there's no stressor effect, and it's and you would still have the same benefit. So to speak, of ketones in in the in the brain, in so yeah, in an organism that cannot properly oxidize glucose in the brain. So yeah.

Mike 51:58
But they're saying it wasn't even the ketones here that was responsible for the effect. It was the microbial changes in the gut. And we've talked, I talked about acromancy At length, in multiple places, and even in the previous study that I was that I was talking about earlier in this podcast series for the the fasting, the fasting beneficial changes were due to increases in akermensia. The beneficial effects of metformin was due to akermensia. The beneficial effects of Berberine was due to met akermensia. And these are all like, these are all literally, like, hormetic, like, love Childs, I guess, for like, it's like, oh, low dose, low dose Metformin, oh Berberine, oh fasting, ketosis. And that's like, well, perhaps it's not through the hormetic reason that people are getting these benefits. Perhaps it's through that that acromania change. And the thing to keep in mind here is that, again, that, and I'll just reiterate it, but increasing or enriching the gut with acromencia, through the variety of mechanisms, increases the gut barrier strength and also mucus lining, decreasing endotoxin leakage into the bloodstream. And essentially the endotoxin, which we've talked about, ad nauseam at this point, is a key component of pretty much every single, almost every single chronic disease, or even even acute disease state, like sepsis, is literally just overload of gram gram or of bacterial endotoxin and bacteria inside the bloodstream. So it's, yeah, we've we have we've talked so now you have ketosis being through this gut mechanism, the fasting being through the gut mechanism. It's kind of like, and we, which we've both talked about before, previously, and especially so if, if the benefits, if the benefits aren't even from the ketones, then, like, there's not even an argument for the benefits from being from the ketones in the beginning, because you could just give compounds that will create ketones. You don't need to move into a like, a completely depleted glucose state, which is kind of what their argument their argument has been, is like, oh, it's carbohydrates. Are the problems? Like, Well, no, the arguments in the research have been for the ketones having a beneficial effect of the brain, but now there's also arguments saying, Oh no, it's actually the gut microbiome. So either way, the Keto the ketose are ketosis. Hormetic argument is kind of moot, like, it's just not, it's not there.

Jay Feldman 54:26
Right. Yeah, and as you're getting it, which is another specific effect here that you see anytime that you're encouraging fat oxidation. So I think you can see this very clearly in diabetes, a state that's clearly characterized by inefficient glucose metabolism, which is what drives insulin resistance. Talked about that before. In that state, you see a lot of benefits from going low carb, and it's not because of the stress caused as you as we've talked about, a huge portion there is likely due to gut effects, but at the same time, you also have relief from an inability to properly oxidize glucose. Properly oxidized glucose. So if you're constantly running through glycolysis and you have this lactic acid production, or lactate production, you're basically in a lactic acid acidosis type state, and you're not able to produce much energy, and you've got all this oxidative stress, and then you restrict the carbs and just shift toward fat oxidation, that fat oxidation will be better. It'll actually be less stressful than whatever you're going through before, and allow for greater production of energy, even though it's more stressful than in efficient glucose energy production or oxidation, it's less stressful than inefficient glucose oxidation. So again, that's another avenue that you can see a potential specific effect here, in really any state where you've got poor glucose metabolism that is, again, not through stress. In that case, it's actually still relieving stress.

Mike 55:50
Yeah, but it's also, I think it's largely there through gut manipulation as well.

Jay Feldman 55:55
Right, which can cause the inefficient glucose metabolism in the first place from all the endotoxin?

Mike 56:00
Yeah, exactly. So you minimize the endotoxin, and you can help to restore what's going on. And then you're, you're essentially, you're not solving the metabolic problem. You're just removing some of the backlog of substrate, right? Because then you're basically just relying on whatever your liver pumps out from gluconeogenesis to supply which, and that's going to be metered. To some extent, you're going to down regulate those glucose oxidation pathways. And so the other thing too is like, yeah, your proxy markers are going to be improved, for sure, because you're not going to like, the backlog has been removed, but you still have to correct that underlying process, because if you if you then want to introduce carbohydrates again, you still and for some people who didn't have issues with carbohydrates before, now you may have issues with carbohydrates because you are insulin resistant from being on a high fat diet for extended period of time. So there's going to be a sticky period where you're in introducing carbs. Again. You got to get things right, which, which we've seen.

Jay Feldman 56:58
Yeah. And how is that insulin resistance caused? It's exactly through the hormetic pathways, exactly through excessive reactive oxygen species and oxidative stress driving excessive stress hormones that causes that what they consider to be physiological insulin resistance. And it does this through what's called the Randall cycle, but the the NAD NADH ratio, the presence of reactivation species are all pieces of that, quote, cycle, which isn't really a cycle that continue, that leads to continuous fat oxidation, without glucose oxidation, which is basically forcing insulin resistance. It's forcing an inability to produce or to produce energy from from glucose effectively or efficiently. So with all of this in mind, I think it's helpful to create some practical ideas for the opposite, the anti hormetic idea that we want to be, minimizing damage, minimizing stress, maximizing energy. And what this actually can look like in real life, what we would do instead of something like ketosis, and also how it works on on, you know, like how it's, yeah, how it looks in real life. And so I do want to mention one other thing first, on the physiological side. I kind of alluded to this earlier, in terms of the androgenic steroid use and and the ability to deal with stressors is that when you're favoring the production of energy and a low oxidative stress, you also have more energy available to deal with stressors before they cause stress, before they activate those backup pathways, before they start causing oxidative stress. You're increasing that that fuel tank, increasing that adaptation energy that Hans Selye described. So again, this being incredibly valuable in improving your tolerance to things that would normally be stressful. And as you were kind of describing people coming from these states normally, first, what you tend to see, just from practical sense, is someone's moving out of a low carb diet, or moving away from, you know, and sauna and cold intergenesis, whatever else is that as you start moving out of that constant kind of stress state, constant hormetic state, you at first, are not necessarily tolerant To stress. You actually will notice the stress a lot. A lot. You'll notice when you start to dip into the stress hormones, when you feel the adrenaline going those kinds of things, and then later on, that tolerance will build up, and it's the initial thing that's happening is not a reduction in tolerance, but rather a it just becomes more noticeable the effects of the stress, because you're not in that constant stress state. And this kind of goes back to what back to what we were talking about earlier. Where is it really a good thing if you can't notice that you're under a lot of stress, like, if you know when people talk about building tolerance to to stress, through hormesis, through excessive exercise, through cold, thermogenesis, through whatever else, to the point that you're able to handle more of those things without stress? Is that a good. Thing to be, to be in, in such a state that you don't even notice these things that are inherently stressful. So that first step that we tend to see, at least in presentation, is first you then start to notice these things. You start to notice when you're going from not being in a stress state to a stress state. But then later on, you'll end up having more tolerance, be able to go longer between meals, sort of thing, without dipping into stress and things like that.

Mike 1:00:24
Yeah. So when you first come out of this stress state, you're you will notice it. There's, there's always a transition period from these types of things. You got to give it a little time. And over time, it progressively gets better. The, I think the biggest thing that I see with a lot of these states, that's the hardest to correct at least, at least for my clientele, has been like a lot of gut issues coming out of these states and trying to get things back on board as far as digestion goes. I think that's one of the things that suffers the most for a lot of people, is these like nagging, lingering digestive issues, whatever it is. And I think sometimes the low carb diets can even make it worse, because I feel like my digestion was a little worse after I did the low carb and all that type of stuff. No, so there's, there's, it's just, there's going to be some, there's going to be some adjustment period coming out of this you saw. But all in all, what I have seen is, like, especially from low carb, people's labs getting way better, coming out of low carb, even though, like, they still may have some lingering stuff going on, like cholesterol coming down, thyroid panels, improving steroid hormone panels, improving devs. I've seen that quite consistently with people just like, like, one after one after one, like, t3 going up. Total Cholesterol going down, LDL, going down, HDL, LDL, ratio. All that changing just with adding in different carbohydrates from not usually from fruit or well tolerated starches. Uh, usually, a lot of people, I've seen so many people's profiles like the cholesterol is like, out of control, coming out of out of the low carb and it's not to say that the cholesterol is causing heart disease and whatnot, but those are, like text, especially the thyroid panels, textbook symptoms of, like, the metabolic dysfunction that's going on. So.

Jay Feldman 1:02:16
Yeah, yeah, yeah, absolutely. And so to take a step to zoom out before we talk about some specifics of what it looks like to to do things from a bioenergetic or anti hormetic view. The first thing I want to acknowledge is that we cannot entirely avoid stress. It is unavoidable. We are always going to, at some point, have to dip into some some amount of stress. And that's not inherently a bad thing, as we've talked about. The biggest thing that we're trying to that we want to do here is weigh the specific effects versus the stressor effects in the context of wanting to produce the maximum amount of energy possible. And so what this means is, instead of trying to do things that where we're trying to drive stress what we instead want to do is choose the things that have the least amount of stressor effects for the greatest beneficial amount of of specific effects, and again, in terms of energy. So we want to choose the things that have the specific effects that allow for the greatest production of energy with the lowest amount of stressor effects. So again, this does not mean that we're that we need to entirely avoid anything that causes stress, whether that's exercise or hanging out the sun or whatever it is, because if we're doing them, if we're choosing them wisely in terms of balancing the stressor and specific effects, we'll be able to choose them in a way that allows us to still maximize the amount of energy we have available and the energy we're producing and minimizing the stress that they cause. So what that would look like would be just as a as a crude example, instead of doing, you know, 10 miles a day of running, maybe it's doing some some short interval training with sprints, where, again, in these two cases, you're going to, like, in the in the intense sprint situation, you're going to have a lot of benefits due to The specific effects of that sort of exercise, and much less stress compared to long distance running. And so we can apply this same conceptual framework to everything that we're doing, from the types of foods that we're eating to, again, the type of exercise that we do, and on from there. So what this certainly means is that we do not want to be choosing things that we're doing just because they cause stress, so things like low carb ketogenic diets, cold thermogenesis.

Mike 1:04:28
Dosing mercury...

Jay Feldman 1:04:30
Dosing mercury, of course, as well as things like resveratrol. And instead, we want to focus on the things that maximize energy production. We talked through a lot of the details for these things through the first seven or eight episodes of the podcast, so I'd recommend going back and listening through those. But just to kind of list through a few of the most important ones. Of course, we talked about how much digestion is, how important digestion is, and how much something like endotoxin and other toxins from the gut inhibit our ability to produce energy. In other words, they're extremely, extremely. Stressful, or drive a lot of stress and really impairability to produce a lot of energy. So for one, we want to be eating things that are generally easily digestible. Two, we want to do the opposite of the low carb diet, where we're actually getting in enough carbohydrates to prevent dipping into that stress, things like gluconeogenesis to produce more carbs. We would want to also eat things that have minimal amount of toxins, looking at things like anti nutrients and nuts and seeds and leafy greens and things like that that are first off going to disrupt our gut and lead to things like endotoxin production and intestinal permeability, but also will prevent the absorption of nutrients and vitamins and minerals and things that we need in order to be able to produce energy. So some some pretty harmful specific effects there from some of those foods, in addition to their stressor effects. Another point I want to make, which we talked about just a few moments ago, is in terms of the polyunsaturated fats and saturated fats, where the pie and saturated fats are really good at amplifying our oxidative stress and at both, both because they become damaged very easily, and also because they produce various metabolites that amplify inflammation, but then also they largely reduce the efficiency of energy production, leading to much greater amounts of stress for much less energy. So instead of those favoring saturated fats and monounsaturated fats, I would say that those big picture wise, of course, there's a lot of details to drill in, but in terms of the diet, I think are some of the most important things from a anti hormetic perspective.

Mike 1:06:30
Yeah, and obviously carbohydrate oxidation, right, right? Yeah. So carbohydrate oxidation, so eating adequate carbohydrates, this doesn't mean you need to go on a zero fat diet. No one's suggesting that, but just not being on the low carb diet. So you find that there's a certain amount of fat that will work for you, that's fine. I would go with that. And then, you know, you may find we've discussed the different amounts of protein, carbs and fats to try on multiple episodes before, and Jay is tired of hearing me say, go through it again. But adequate protein, adequate carbs, adequate fats, moderating your exercise. So kind of auto, auto, self regulating it, as far as you know, doing just enough for the specific effect, and not really dipping into that point where it's too much. And that's always going to adjust based on what you go, what you have going on in your life. So it's hard to perfectly plan it minute, you know, getting adequate sleep, get meeting all of your micronutrient requirements, calcium, magnesium, all the fat soluble vitamins, saying copper, everything there, and not trying to just get one specific mineral that's the super important one, and all the other ones are bad. No, they all. All of them are all of them are required in certain amounts and certain ratios, whatever it is. And then, you know, sleeping regularly at night. I think another really important one is community and relationships. It's all going to come down to a lot of these basic factors, and then just a lot of so while doing certain things is really important, avoiding a lot of dumb things is also really important, like, like, like, just a lot of some of these hormetic stuff that goes on, like, like, going through cold thermogenesis all the time with, like, going into those, like, negative 500 degree tanks, or whatever it is, on a regular basis. Or, like, I don't know, like, long, like, days on days of fasting, or, like, only eating four days a week, or three days a week, or five days a week, whatever it is.

Jay Feldman 1:08:25
Even the classic 16, eight intermittent fasting.

Mike 1:08:30
Yeah, it will. I only get stipulation to have out that is some I've seen people who've had, like, seriously terrible gut issues like do that for just a short period of time to manage symptoms until things could get situated. But on a long term basis, there's just, like, there's, I think that there's, perhaps it's just me, perhaps, perhaps just my thought process, something. But some things are just just, don't even sound good, right? Like, I've had people come to me like, I'm only, I only eat four days a week. Like, so you don't eat three days like, just like 24 hour fast. It's like those. Those aren't longevity strategies. That's starvation.

Jay Feldman 1:09:08
It's not effective ones. I want to say also so in terms of something like the fasting, if it is beneficial in the short term, that's a situation which I think is common, where you're seeing those stressor effects being more beneficial than the sorry, the specific effects being more beneficial in the stressor effects. But of course, if they were to do it over time, those stressor effects would really accumulate and cause some issues. So yes, it is a short term option. I think in the vast majority of cases, there are better short term options than fasting to help bring gut relief. But I'm sure in some severe cases that can be the case.

Mike 1:09:38
And avoiding like, taking like, low dose metformin and like other obscure drugs and compounds that, yeah, are questionable from their mechanism of actions, or questionable from their effects, or are risky. And I think a lot of in my in my experience of things, a lot of times it's just avoiding a lot of stuff as. All is because the general things to do are kind of for, you know, they're everybody has specific stuff going on, and that's gonna, like, it's hard to give, like, a tailored response here. But as far as, like, the baseline of things, like, it's always going to be the same. Make sure you're eating enough, make sure you're sleeping, make sure you're reaching all of your micronutrients. Relationships are important. Getting some type of movement in the day. It doesn't have to be weightlifting. It could, you know, it depends on what your goals are, if you're, if you're a 50 year old guy, and you just want to be in good health and have some community, you know, you could do some type of martial art, and your dad likes pickleball, or all these like, Whatever, whatever type of community or sport or activity that you enjoy doing, whether it could be hiking, whatever it is like just, just doing that on a regular basis. Fine. You know, the a lot of them are basic recommendations that we've got, that we've gone over ad nauseum. But there's a lot of, like, what we kind of went through. I think the most here is talking about, like, the different situations where, like, you do not want to do these things. So like, stay away from these things as longevity strategy strategies.

Jay Feldman 1:11:06
Yeah, yeah, definitely. So I think those are great points, you know, in terms of being active and looking for movement, for the sake of enjoyment and social interaction, and, you know, things like that, and the way it makes you feel, as opposed to this idea that you just need to burn as many calories as possible. And that the more calories you burn, the better you talked about why that is not a very effective way to look at things like fat loss in the past. So I'll link to those episodes. But yeah, just in general, exposing ourselves to stimulating environments, rich social interaction, things that are not stressful, but have immense benefits. You know, you mentioned fat oxidation not being a problem, or fat intake not being a problem. We don't need to be on a low fat diet. And I did want to clarify again that fat oxidation under a state of low energy demand is fine. You know, muscles at rest don't need much energy. They can produce fat without dry without or produce energy from fat, yeah, oxidized fat without dipping into a stress state. Now, when they don't have a choice but to do that, and then have to activate stress because there's no carbs available for higher energy demands, that's a problem. Or for other areas of your body that can't run on that low energy demand, they have much higher energy demands, whether it's your brain or liver, kidneys, whatever those are situations where you need to you want to have the carbs available to not dip into the stress you mentioned, sleep, like getting adequate sleep. It's funny that some of these things are never talked about in favor of those with hormesis. That you know why? Like that people don't suggest sleep deprivation in a mild way for all of its potential hormetic benefits, or, like, trying to get into really nasty fights with your significant other, like relationships and things, just for the hormetic effects. So yeah, I mean, these are all things. Of course, there's you know, being a little facetious here, but in reality, getting enough sleep is massively beneficial due with specific effects, not due to its stressor effects. Getting the right amount of sleep is not stressful. And the same thing with having, you know, good relationships, minimizing psychological stress, there's not benefits to getting the right amount of psychological stress, meaning, like some substantial amount, you know, same thing with like exposure to toxic substances, you mentioned, mercury, various chemicals and ionizing radiation and things a lot of people talk about non native EMFs. These are not things that are beneficial in low doses. These are things that are beneficial with minimal like, the less the better, right? And so these are things that we want to be minimizing our exposure to, not trying to expose ourselves to some small amount for hormetic benefit, which, again, most people don't talk about now, but back when hormesis was coming about as a as a scientific concept, that's what people were suggesting that that should be done. So yeah, I think you're right. It's more of a of the most important thing is, is not doing things or avoiding the things that are inherently stressful and don't have those beneficial specific effects, and I think that, yeah, beyond that, it's, it's a lot of a lot of other other basic foundational components to health that we've discussed a lot.

Mike 1:14:10
Yeah, but we've gone over numerous times, and we there's resources available for them, on on both of our websites and on all the podcasts. I think it's all free, nothing charge for so those, as far as, like, what you can do currently, that's out there. The hormesis piece is like, what to kind of stay away from right on a regular basis, and do not get get caught up with. And then essentially, it was us breaking down. These are the individual points. And these are, like, the problems with those individual points. And then here's, here's alternative perspectives to look at things through and to consider if before going down any of those, any of those routes,

Jay Feldman 1:14:49
Yep, yeah, absolutely. All right, that's going to wrap up our hormesis series. If you did enjoy it, please leave a like or comment if you're watching on YouTube, and if you're listening, I'll. Where please leave a review or five star rating on iTunes. All of those things really do a lot to help support the podcast and are very much appreciated. To check out the show notes for today's episode, head over to Jay Feldman wellness.com/podcast where you can take a look at the studies and articles and anything else that we referenced throughout today's episode. If you are dealing with any low energy symptoms, maybe this is chronic cravings or hunger, low energy or fatigue, joint pain, weight gain, digestive symptoms, brain fog, poor sleep, hormonal imbalances or various chronic health issues. Then head over to Jay Feldman wellness.com/energy where you can sign up for a free energy balance mini course, where I'll explain how these different symptoms and conditions are really caused by lack of energy, and I'll also walk you through the main things that you can do from a diet and lifestyle perspective to maximize your cellular energy and resolve these symptoms and conditions. So to sign up for that free energy balance mini course, head over to Jay Feldman wellness.com/energy, and with that, I'll see you in the next episode.