The Delicate Balance Between Oxidative Stress And Antioxidants

Most wellness advice tries to stamp out oxidative stress. We make a different case: the right dose of stress is the signal that builds resilience. From the first snowfall chat to a deep dive on electrons, mitochondria, and energy flow, we walk through how redox balance—reduction and oxidation—is the unseen driver of better fitness, metabolism, and healthy aging. Rather than drowning your cells in pharmacologic antioxidant doses, we show why whole foods, intelligent training, and hormetic practices switch on the body’s superior, built-in defenses.

We break down how reactive oxygen species act as messengers that activate NRF2 and tune NF kappa B, leading to stronger antioxidant enzymes like superoxide dismutase, catalase, and glutathione. You’ll hear why studies on high-dose vitamin A, E, and isolated polyphenols have disappointed or even backfired, and how funding bias confuses the supplement hype cycles. We connect these insights to practical levers: balancing training intensity to avoid chronic overreach, using time-restricted eating to spur ketone-driven repair, and introducing sauna, cold exposure, and real daylight to enhance mitochondrial function and recovery.

Food-first takes center stage. We discuss the risks of seed oils and excessive polyunsaturated fats on membrane stability and oxidative load, plus simple swaps toward olive oil, avocado, and nutrient-dense whole foods. Micronutrients like selenium, zinc, and sulfur amino acids matter because they power your endogenous antioxidant systems. The goal isn’t to smother the flame; it’s to keep a steady candle that signals adaptation without tipping into a wildfire. We close with a n=1 approach—listen to energy, sleep, and training feedback—and small experiments that reveal your best balance.

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For video, open access reference papers and PP slide deck go to: www.thehealthedgepodcast.com

Transcript

Snow, Season, And Today’s Theme

SPEAKER_01 0:00

Welcome to the Health Edge, translating the science of self-care. I'm Dr. Mark Pettis, and I'm with my friend, Dr. John Bagnulo. John, good morning, my friend.

SPEAKER_00 0:10

Hey, good morning, Mark. It's great to see you. I know you got snow as well.

SPEAKER_01 0:14

Great to see you. The snow season is here. Yeah, we got about six to eight inches of fresh snow yesterday. And um all the I'm reminded that so much of our local regional economy depends on snow. And so all of our ski areas and uh the cross-country enthusiasts and uh are all celebrating and with the Christmas holiday coming up, it's uh nice for there to be snow on the ground, and hopefully it'll still be there in a few weeks.

SPEAKER_00 0:45

Yeah, hard to say.

Redox 101 And Why Balance Matters

SPEAKER_01 0:47

Yeah, hard to say. Uh so we have what I think is a uh terrific topic for discussion, John. And and there's so much health information out there today that that you know we all know of, and um uh a lot of um uh resonating themes that I find when I look at at some of the uh the sources that I like to go to for podcasts and and real quality, uh credible information. And one of the themes that I don't see discussed a lot in those um traditional and very popular circles is this uh topic of redux, reduction and oxidation, and the extent to which redux pathways systems in human biology, like all biologic systems, are very, very finely tuned. Uh, and that fine-tuning can make all the difference with respect to not having too much oxidative stress, uh, not having too much of reduction and what might be the form of megavitamins and antioxidants, which have become such a um a meme in uh in the supplement world and marketing, and uh and so I I think like all that we talk about, this is a very nuanced topic. And uh we'll go through a little bit of that research. But I'm really glad you brought this to my attention, John, uh, because I haven't thought about it in a while. And um I I think these pathways are things that we can we can influence very significantly. And our our objective today would just be to give the average health edge listener a kind of a 101 overview of what we're talking about with Redux. Um what are our um uh internal pathways that can help with that balance and what we can do to allow those systems to work for us.

Exercise As Beneficial Stress

Antioxidant Hype, Funding, And Evidence

SPEAKER_00 3:00

Yeah, yeah. No, it's it's I I know most of our listeners would would identify with the the notion that we have such a monolithic society, right, in so many ways. We we get a direction, we get an angle, and we just go with it until you know, till the extremes. And I think when you get into this discussion around oxidative stress, kind of neutralizing it, right? Because we know that oxidative stress is associated with aging and some deleterious effects on cellular health and our mitochondria and all these things that we want to like throw a wet blanket on that little fire that we actually need to have burning at a at a low rate. And and I think you know, exercise gives us so many benefits, and I think people appreciate those benefits. But I don't know as though the average person understands where those benefits start with exercise. And it's it's the stress, it's the dose of the stress that you create, it's the dose of the damage that you create to the myofibrils of the muscle. It's all those like low-level damages and oxidative stress, you know, having higher levels of reactive oxygen species as a result of exercise brings about the very favorable changes that we want. And I I don't just I don't think people understand that you're you know, you're actually trying to elicit a physiological response by causing some low-level inflammation, some low-level oxidative stress, some some you know, low-level tissue damage from which you're gonna come back bigger, stronger, more adapted to that type of exercise. And, you know, the the magnitude of the response you get in exercise to a large extent is the result of this U stress, this favorable stress, right, that we're creating. So I, you know, for me it's fascinating, Mark, because you just said it really well. We we're bombarded with, you know, whether it's marketing or whether it's published papers. And sometimes that's a blurry, and and I don't know if everybody appreciates how blurry it has gotten. But when you look at, when you look at the published papers, let's say, on a particular antioxidant, we could use resveratrol as an example, you know, someone is funding that typically, and it's, you know, to a large extent, it's the manufacturers of a resveratrol supplement. And I'm not picking on resveratrol because it's a fascinating molecule. And and don't get me wrong, I mean, I think it it there's certainly benefits to ingesting resveratrol. I think the dose might be the you know, really that the missing component to that conversation, but we could say this about any antioxidant that is manufactured and then sold. It's a huge industry, right? So when you when you look at all the published papers on on different types of antioxidants, if you look closely, you know, they often, you know, they'll often identify the funding, and you you'll see that it's a manufacturer, uh either a supplement manufacturer, a particular, you know, brand name at times. Um and there's look, there's nobody, there's nobody at this point in time, there's nobody funding, you know, for the most part, a study on, you know, looking at the consumption of, you know, let's just say Concorde grapes, right? It's going to be on resveratrol. And so that's where I think the the whole playing field has really become tilted so that we're we're bombarded with marketing on antioxidants, on particular supplements. And often papers are cited as evidence that yes, this antioxidant will have this effect. But they might not share with us all the other papers that either showed no effect or very surprisingly, um surprisingly, you know, effects which would make you question whether or not you want to even take the supplement in the first place. So yeah, it's it's fun. It's a fun topic because it weaves together so many facets of lifestyle, exercise, you know, choosing the right foods on a regular basis. But to your point, Mark, understanding this oxidative, reductive uh process that's always ongoing and how you got to try to maintain balance and not let it get, you know, too far one way or the other. But it's all about, hey, it's all about electrons. This whole, this whole conversation is all about electrons. And I think that will benefit our listeners too, understanding that that's really that's like 90% of energy production, health, um, you know, the health of our mitochondria. You can go in just so many different ways when you start saying, look, it's all about electrons. That's what this conversation really comes down to.

Electrons, Mitochondria, And Energy Flow

SPEAKER_01 7:50

As we will share a few slides uh illustrating that, John, it that's that's great. And it really does kind of bring us back to the to the principle that uh humans are electrical organisms, uh, much as everything in our universe is. Um Nikola Tesla, uh, just sort of inherently over a hundred years ago knew that to understand electricity, the flow of electrons, was to really uh unleash uh a much clearer uh understanding of how our universe works and and certainly how human biology works. And though that may seem like a bit of a leap, uh that's really what we're what we're talking about here. And uh reviewing this topic also made me think of I I believe it was the great psychiatrist Carl Jung that once said, that which doesn't make you stronger, uh that that which that which doesn't kill you will make you stronger. And uh and uh I think what we'll uh just illustrate as we go over these slides is that this uh uh human biology and the minute, tiny, tiny, low levels of molecular signaling uh becomes essential uh in managing the yin and yang of of our of our biology, oxidative stress and reduction, the sort of the response to that stress. And um that uh because something might work in the lab uh uh or be suggested to to correlate epidemiologically, more of that something, as there are many historical examples of, uh, can be really detrimental and quite harmful. And we we've certainly, as we'll touch on, we've seen that with um uh good randomized control studies that it have, for example, have looked at high doses of vitamin A, uh only only to stop the study suggesting that there might be actually a greater prevalence of lung cancer in people at risk who take high doses of vitamin A. We've seen uh that vitamin E in very high doses has had little uh uh uh benefit, if any, at all, and in some examples might have worsened outcomes in cardiovascular disease, where where it was widely studied uh some some time ago. So these are outcomes that surprise the research community, because um, if something works mechanistically, you can demonstrate it maybe uh at a certain dose. Uh it just does not often extrapolate well to human biology, particularly and health, when you get into those more sort of pharmaceutical um doses of what might appear to work really well at a minute dose. And and so it it is a great biologic principle to keep in mind. More is not necessarily better. Um and we've got to be.

When More Antioxidants Backfire

SPEAKER_00 11:18

Yeah, I think that yeah, Mark, what you just said, I mean, the pharmacological, pharmaceutical type dose is again, that's just so unnatural. I mean, that's a that's a word that I know people often take issue with, the word unnatural. But when in the context of a biological system, like what we're talking about here, whether it's redox, you know, reactions at the mitochondria, wherever it is, when you're talking about that type of dose or exposure to an antioxidant, you know, something that's going to donate massive amounts of electrons and completely put out the small flame that you need to kindle positive effects, it's so different than eating a food that would contain modest amounts of whatever, say, antioxidant is we're talking about. And, you know, the first time I ever encountered this, um, I was 25, 26 years old. I was I was doing some graduate work and I was studying blueberries and the effects of blueberries on on human health and in particular women's health. And I was um I was talking with the late James Joseph at the Tufts University Center for Aging, where, you know, Dr. Joseph did he did so much research on blueberries, spinach, walnuts, you name it, all of the foods that in the 80s and 90s, researchers were identifying antioxidants that were really potent, right? They could really quench free radicals, they had the unique ability because of their ring structures to give up electrons easily. And he was finding in animal studies that all of these foods, at you know, like three to five percent of an animal's diet was extending life. It was, you know, the food, we're talking about, you know, typically freeze-dried powders or fresh concentrates, they were, you know, changing, changing things at the cellular level in a favorable way that would offset the aging process in, you know, the lab in the animal. Um, but this was the interesting part. When they took the antioxidant out of the blueberry and they gave the the animals just straight anthocyanins at doses that were similar to what they would have acquired from food from the three to five percent of their diet, or at higher levels, that the animals that they didn't see any benefits in those animals, that they actually died at a younger age than the animals that got the control, that didn't get any antioxidants. So, you know, I think from from early on, I started to question, you know, how much can supplements or how much can these isolated molecules, to your point, administered in more of a pharmaceutical fashion at pharmacological doses, unnatural to what our genetics would have ever encountered. You know, how much can we really it's a gamble. I I honestly I I don't think uh we can predict, um, but I think we can question the not only the efficacy and if they're gonna be able to change things in a in a favorable way for us, I think we can question their safety from what you just shared with us. You know, a few of those studies, and we have some others that we can we can show our listeners that are more specific to exercise and the benefits that you would hope to get from exercise that you don't get when you take a mega dose of a particular antioxidant. So it's just uh, you know, it's an amazing, again, it's it's an amazing topic because of how much it weaves into the discussion.

Endogenous Defenses And NRF2

SPEAKER_01 14:49

Great. I'm gonna pull up some slides, and I apologize for those that are just listening to our uh podcast. But if um if you are interested, the slide deck will be available on our uh website, the healthedgepodcast.com. We do have a a YouTube channel um with the video content for those that want to maybe see the graphics that we're sharing, and I'll do my best uh to describe these. But I'll I'll pull these up, John. And um there the intent here is to just offer kind of a 101 uh definition of of redox, what we're talking about, and then we'll look at we'll look at a few of the studies that we're uh referencing in terms of these principles. But just to start with redox, right? We have reduction uh and oxidation. So this this is sort of the yin and yang of of how we uh donate electrons and the example of reduction uh and how uh you know we we uh uh lose an electron when we confront an oxidative challenge or stressor. So this homeostasis, this back and forth, uh is uh important in human health as a very dynamic equilibrium, right? Essential for all biologic processes and just a few here that we often talk about on the health edge. Energy production, you you reference mitochondria. This is a uh uh a huge um uh organelle around uh energy signaling and redux sensing. Uh, this is where, right, all of the electrons from the food that we consume are ultimately converted to energy. So it's a very active uh redux system. Uh cell signaling, how our cells communicate, our immune response. You know, we might call that inflammation if it's not well regulated. Um and so maintaining this balance between oxidants, and we'll look at this in a little more detail, and antioxidants is critical. And balances in either direction can lead to cell damage, disease, and aging. And that's so important, right, John? You rarely hear anyone talk about the potential risks of pharmacologic dosed antioxidants, and and that's really what we're talking about here.

SPEAKER_00 17:27

Yeah, you rarely hear somebody say, well, you need a little more oxidative stress.

Adaptation Examples: Lactic Acid And Fasting

SPEAKER_01 17:32

Yeah, exactly. And this is uh again a simple schematic. Uh when when molecule A uh loses an electron, that's oxidation. And uh when uh another molecule picks up that electron, it is reduced. It is uh uh a reduction. And so this is really uh flow of electrons. This is uh electricity, which is uh flow of electrons. Uh and certainly there are areas in the body like the mitochondria where this is super active and super important. And just to uh uh kind of reiterate what we've been talking about, uh John, you know, energy production um in the mitochondria is obviously fundamental to human health. And and as we've talked about often, um virtually every chronic complex disease, from uh degenerative neurologic diseases to obesity and and diabetes, insulin resistance, all demonstrate um alterations in mitochondrial reducts. And so this is obviously uh an important area of human biology, um cell signaling and regulation, as as I know you will elaborate on in terms of exercise, um, John. You know, we know that uh in the example of exercise, when you're creating purposely these reactive oxygen species, um that dose will lead to a response. These are these are these free radicals are messengers, and our body senses these messengers uh and and will then turn on the body's response, which attempts to keep that oxidative stress in check. And we talk a lot about these responses, particularly how lifestyle can adversely or positively affect systems like NRF2. These are transcription factors that were that will activate your book of life. It turns on many chapters in our book of life that can help with detoxification, uh preventing that inflammation from going over the top, uh, to uh protecting our DNA. And and so these this is a response to those oxidative and reactive oxygen species signals. And so um this is why uh you know uh a purposeful creation of stress in this example is one that produces many positive effects because you activate these systems. And what always comes up for me, John, uh, when I think about these systems is that we have built into our design pretty much the antidote for anything that modern life can can throw at us. Um these these systems are highly evolved uh in all mammalian um and and many non-mammalian life forms, and they are um beautifully uh um responsive uh uh when the stimuli are adequately triggered. And so part of the part of the challenge for us is we have the software, but modern life and and our and how our lifestyles translate often don't allow that software to activate. So you know, we have these state-of-the-art, right, operating systems. Um, we don't need to upgrade our software, you know, every six months, as you might, with your you know, your your laptop. Um these systems are are so finely tuned, but they require uh uh they require having adequate signaling to enable that.

Modern Mismatch And Micronutrients

SPEAKER_00 21:47

So um, and and you know, Mark, to add to that, I mean, you know, the way you identified, you know, some of the cell signaling here, how it controls the transcription and production of proteins, you know, a lot of those proteins and enzymes have incredible antioxidant, much more so than anything we'd ever eat. Right? So again, it's one of those things where we are so focused on the exogenous source of antioxidants that we don't really appreciate what we can produce endogenously if we allow that stimuli to persist at a low level. And it's you know, it's not just it's not just at that level with the electron component to this and and neutralizing oxidative stress with the enzymes that we can produce. It's also things as simple as lactic acid. I mean, you know, lactic acid, if we constantly expose our tissues to it, we start producing, you know, lactic acid dehydrogenase enzymes and versions of those enzymes that are really um really effective and work very quickly on converting lactic acid back to energy to something we can use. But, you know, the the analogy I always use that's been demonstrated is people that take baking soda to neutralize lactic acid, well, they don't get that adaptation. Um they might get, you know, they might neutralize the lactic acid in that short window, and it can allow them to say, you know, sprint an extra hundred meters or an extra 150 meters. So at the time of competition, it's understood. And you can see the value in that. But in terms of training and helping the body adapt, the baking soda is actually counterproductive because it's preventing the body from experiencing the effect and the stimuli that that lactic acid will produce, not just for skeletal muscle, but for heart muscle. So, you know, that's just another example of a favorable stressor that we're creating. And it's the the amount of that stressor that washes over tissues, ultimately controls, you know, whether it's going to be harmful or it's gonna be beneficial. And it can be very beneficial, just like these reactive oxygen species can. So I love the way you that you, you know, you always go back to the blueprint that we have, right? We've got this amazing blueprint physiologically to adjust, to adapt, and to become stronger versions of ourselves with these levels of U stress, these favorable stressors. So, you know, it's just always keeping that in mind and not trying to override um the amazing blueprint that we have.

Hallmarks Of Aging Through A Redox Lens

SPEAKER_01 24:27

Yeah, that's such a great example, John. I really like that. Uh and another one that that comes up for me uh is you know, when you look at fasting, intermittent fasting, fasting, time-restricted eating, yeah, we know that uh the stress from uh, let's say, food or energy deprivation uh you know leads to right to these adaptive responses producing ketones and how uh you know, historically, and and even today, I think we continue to look at ketones in the example of fasting as you know, dangerous, you know, this is and I'm not suggesting that fasting should be done without without a thoughtful plan and um maybe monitoring for some by a professional, but for the most part, you're activating systems that that are alive and well in us and have been for hundreds of thousands of years. And so here you see ketones as a responsor, uh as a response to the stress of a fasted state that unleashes right this whole host of benefits. And when one can begin to leverage low-level stress as a way of activating the software that's alive and well in them, but maybe dormant, um uh that's that's where the magic begins to occur. And um, this next slide, John, um uh and and the articles from which these slides have been uh pulled, I'll also have on our uh website uh the open source articles that are available. Uh uh, but this again, you you mentioned, John, that you know, our our uh antioxidants can uh come from our endogenous internal systems, and and the real geeks that listen to us hear about these uh powerful antioxidant systems like superoxide dismutase and catalase and glutathione, uh really important um endogenous systems. Uh and we know that that oxidants, those prooxidants, those things that cause oxidative stress are often just natural metabolic byproducts uh which then stimulate these endogenous systems. And and one of the great challenges in modern life, you know, we often talk about the the uh sort of gene environment mismatch, the the extent that modern life now confronts us with oxidative stresses that no human perhaps before us has experienced from the processed, ultra-processed standard American diet to the sheer volume of pollutants and you know, smoke and ozone and sedentary states, and right, these are incomplete lists, right? Uh non-native light sources, things that we talk about all the time. So part of the challenge in modern life is the oxidative stressors are greater than what historically we have been adapted to adequately uh manage and regulate. Uh and this is where our endogenous systems, even when they're working overtime for us, uh, can't always keep pace. And and it's that it's that mismatch that ultimately may lead to what we would call a disease, like type 2 diabetes or Parkinson's or Alzheimer's or cardiovascular disease. And so um this has relevance for all aspects of lifespan, disease risk, certainly quality of life or or health span.

SPEAKER_00 28:29

And so many of those endogenous antioxidants are nutrient-dependent. So you may have the stimuli, you may have the stress, the reactive oxygen species that you're generating from the mitochondria when you run, when you train. But even with the stimuli, either you don't have the sulfur-containing amino acids like cysteine and methionine to help generate some of these, or you don't have the zinc, let's say, to produce the superoxide dismutase, the selenium to produce the glutathione peroxidase. So that's where micronutrient deficiencies can also prevent us from having that endogenous antioxidant production or response that would be ideal, as you said, to keep up with kind of the modern load here and some of that allopathic uh reactive oxygen species load.

Practical Levers: Fats, Training, Heat, Cold, Light

SPEAKER_01 29:17

Yeah, that's a really great point, John, right? These systems require adequate substrate in order to uh to function in an effective way, and maybe more so now than ever, just given the burden of oxidative stress that that we confront. Uh and this is just um, again, these graphics, I I apologize for those that can't see these, but this is just an example that we touched on of how reactive oxygen species, regardless of the sources for them, are messengers. And in this graphic, uh the messengers activate the Transcription factors that we talked about, like NRF2, they might alter the expression of NF kappa B, right? A kind of a pro-inflammatory transcription factor, which you want turned on in response to an injury or a pathogen, like uh, you know, resistant staph aureus. This is where you know um NF kappa B becomes a lifesaver. Uh but when 24-7, uh day after day, week after week, uh these systems are skewed uh and and poorly regulated, um, you know, once we get into sort of chronic inflammatory states, uh, you know, we know that that's a kind of a passport to aging. So this it's remarkable, right? How the small molecules that um uh you know get above top secret access to our cell nucleus turns on these transcription proteins, which are uh can sense that higher reactive oxygen uh reduct state, and and and then they produce the proteins, right, that that you would ideally want to reconcile that um that challenge. And here we with exercise, John, and I'm gonna I'm gonna let you uh run with this, but um um and I'll make sure this paper gets uploaded, but all of the benefits of exercise, right, can be traced to the reactive oxygen uh response um to that that level of stress uh in ways that you know these pharmacologic doses of supplements uh are not going to be able to reproduce.

SPEAKER_00 31:59

Yeah.

unknown 32:00

Yeah.

N=1, Intuition, And What’s Next

SPEAKER_00 32:00

I mean the mitochondria, again, they're front and center in this conversation. But you know, if we looked at the fundamental unit of a muscle or a sarcomere, we could start to get into some other areas as well in terms of microfiber changes or damage with resistance training. But at the end of the day, you're challenging a muscle to either produce more energy, you know, again, albeit it's dependent upon oxygen and blood flow. So you that's where the cardiopulmonary component comes into, let's say, aerobic responses or training. But at the end of the day, you're you're asking a muscle to extract more oxygen from the capillaries that are around that. And but the mitochondria are what's going to ultimately generate that energy. And mitochondria, like that's where the flame burns the hottest when it comes to reactive oxygen species and generating them. So when we're when we're producing massive amounts of free radicals, because we're asking the mitochondria to produce so much energy, and there's just so much electron transport or exchange taking place there, the mitochondria adapts. And you'll see that mitochondria that are trained, let's say, in an athlete or in a person that has embarked on a training program, their mitochondria are more resistant to the oxidative stress associated with that energy production. Now, that takes place over time, but every bout of training results in those mitochondria becoming a little more resistant to oxidative stress. Now, how does that equate to better health? Well, we might exercise for an hour a day. We might exercise for three or four hours a day. It really depends on a person's lifestyle or everything that goes into that. But the other, let's say, 23 to 20 hours of the day, you are in a positive redux state. So you have less oxidative stress, right? You have things tipped in your favor. You survive the bout of training, you adapt, and then you reap the benefits of that for the next cycle. Um and that's, you know, I think a big part of the story is that we're causing low-level stress with exercise. But the stress has so many advantages because downstream from that and for a bigger window of time, we're going to be in a better place in terms of our ability to resist some of that damage. Um, you know, that so not to oversimplify it, but that's a you know, that's really a big part of this. And if we blunt, if we blunt that stress, right, if we prevent those free radicals from spending the minute amount of time around that mitochondrial membrane, if we blunt it too fast, we never get that response. And that's why we don't, we we see in some of the studies, we can talk about these that have been done with resveratol is the one that I know off the top of my head. I think vitamin C, and you talked about vitamin E as well, um, specific to exercise, that those athletes that take the mega doses, or we could call them more pharmacological dose, never, never um do I want our listeners to think I'm suggesting we shouldn't eat vegetables and and fruits or use curry in our cooking. Or I mean, we we get like very significant amounts of antioxidants from those types of foods as well as from the coffee that we drink. You know, we're getting antioxidants, hopefully, if our diet is, you know, is constructed appropriately, we we get antioxidants on a consistent basis throughout the day that help offset some of this tide of reactive oxygen species. So we're trying to we're trying to take care of some of that fire, but we don't want to put it out completely. And so I want to make sure I'm really clear when I say it that way. Um in with exercise, athletes who take a mega dose of antioxidants, they blunt that the the favorable response. Um, you know, so yeah, it's not just about like longevity and it's really also if we could look at it, the very short-term effects of how you may prevent a favorable adaptation to a particular type of exercise because of just not enough, again, not enough oxidative stress at a low level calling for for favorable changes.

SPEAKER_01 36:28

Yeah, that's that's great, John. Uh and a common example to really share that that uh that teaching point around uh just uh a few more quick slides and then we'll we'll wrap this up, John. Uh and really to kind of emphasize uh a point that you were just making, the when you look at those uh, you know, there are many dietary antioxidants that we hear about all the time. And when you obtain those in the packages that nature has produced us with, which by the way, often have multi you know, a multitude of these ingredients. So uh, you know, when you're getting a uh a nutrient-dense uh vegetable, you're getting uh often multiple antioxidants as opposed to sort of pulling one out of that of that plant and and then you know super concentrating it and then taking it in an encapsulated form. But I I like this because when you when you look at typical sources of these well described uh antioxidants, in nature they tend to occur in much lower doses. Uh this is milligrams per hundred gram of of food consumed, compared to what you see in these more pharmacologic doses of um uh sort of antioxidant extracts, if you will, which continue to probably be one of the more popular over-the-counter supplements that are um you know purchased by by people. And then and then lastly, and uh this is kind of a uh a summary slide from a very recent uh paper uh pulling some of this together, how right, the the this balance uh is so uh um intricately integrated with every aspect of of human biology, and and many of these now known to be hallmarks of aging and quality of life. And and we've talked about some of these from mitochondrial function and how cells regulate uh themselves, including cell death, uh, what we call apoptosis. And there's a lot of interesting research now looking at senescent cells, cells that are aging, but they're just they're not taking themselves out of circulation uh in a timely fashion. And so the process of programmed cell death, which is important for human health, as these cells become more dysfunctional, becomes disrupted. Every level of, you know, we we've talked uh many podcasts about insulin resistance being one of the true drivers of all chronic complex diseases, inflammation. These are really the accelerants of uh aging, poor quality of life, intestinal barrier function, right? Leaky guts. We don't I don't think typically, at least in the in the clinical world, we think of these as being so tightly connected to these redux systems. And then from you know, aging as we've talked about to degenerative neurologic diseases, cardiovascular diseases, um, and then you know, DNA. We've talked a lot in prior uh podcasts about epigenetics, uh, you know, the ability for DNA to repair itself in response to oxidative stress, uh and um and and the very active ways in which a holistic, healthy lifestyle can optimize those systems so that we become less vulnerable to uh DNA damage that might ultimately translate uh into a disease state, or the epigenetics, the the expression of our book of life, which, as we've talked about, has many possible expressions. Uh our our book of life is is hardly a fixed trajectory over which we we blame our genes and and say our prayers, right? Not a very effective strategy for embracing life. Uh and then lastly, we we talk a lot about protein structure and how you know once the structure of a protein changes, everything about the function of that system will become impaired. And so these these systems are so um uh important in maintaining this uh homeostasis, this uh regulation. And uh uh if if if you were going to summarize this, John, in terms of uh and we've touched on some of these things uh over the over this discussion, but uh from a lifestyle perspective, um and again, this you know just sounds like um stuff we talk about all the time because it's the same playbook. Um how how how might this uh science guide uh in a practical way uh how you would help someone, John, struggling with their health?

SPEAKER_00 42:08

Yeah. I I think it's good to look at the sources of oxidative stress in one's life. Uh and you can look at this in a lot of different ways, but don't look at the oxidative stress that's generated by exercise as being the primary cause of an imbalance that you may have, right? I mean, I I you know I like to look at things like the amount of polyunsaturated fat that maybe we're ingesting inadvertently through a lot of what might be, you know, foods with some good virtues, some good characteristics. You know, we could talk about, you know, different types of nuts and seeds, and then we can get to areas that, you know, I think people should be really vigilant and cautious around, would be like seed oils, right? If you're consuming, if you're consuming like sunflower, safflower oil, corn oil, canola oil, and all these polyunsaturated rich oils, then you're making your mitochondria essentially out of a very flammable type of fatty acid that's gonna generate massive quantities of reactive oxygen species when it's washed with with the with what you generate in in the mitochondria and energy production, right? So, you know, I look at that, for instance, as being a lifestyle uh a lifestyle component, the types of fats we choose and ultimately that we build our organelles, our mitochondria and our phospholipid bilayer out of. You know, I look at that as being a major determinant in the amount of oxidative stress that we're going to experience. And it's gonna really have an effect on the aging process, whether it's neurological, whether it's cardiovascular. I mean, there's some really interesting papers out there on what happens when we become too polyunsaturated fat uh comprised, right, from all those fats. You know, like there's an area where you can take more control over reactive oxygen species and not let that candle, which you need, don't let that candle become a brush fire or a wildfire and it's burning out of control. But let the candle burn. Let don't put the candle out because you're gonna need that. You need that little bit of it's gonna really catalyze, it's gonna, it's gonna drive very favorable effects in the body. So keep the candle burning. Don't put that out and prevent the brush fire with some lifestyle characteristics that are gonna have a far, far uh more favorable effect widespread, which would be, you know, the types of fats you eat, stress reduction, right? Whether that's through meditation, um, practicing gratitude, that's gonna keep your oxidative stress levels lower. You know, find that balance of exercise where, you know, you're you're in the right intensity. So you're not always zoned for asking too much of, like, let's say, a cardiopulmonary response, you're getting too much cardiac stretch, you're starting to get calcium leaking out of the cardiac tissue. That's when you've, that's when it's excessive. You know, all the studies on exercise, and you and I have talked about this, Mark, show that, you know, people who walk or run somewhere between 30 and 35 miles a week, they seem to have a better overall trajectory of health than people who run 50 or 70 miles a week. Is it too much stress? You know, I mean, I think that's where we can go there uh pretty quickly when you start to look at some of the very interesting studies, albeit a handful, that have been done by guys like James O'Keefe, you know, who's uh I think an awesome, awesome cardiologist because he asks those those questions about what's too much of a stressor on the heart and what are the effects of too many polyunsaturated fats, specifically when they're incorporated into cardiac tissue. Um, so we can go in those directions for very, I think, very attainable lifestyle changes. Find balance with your exercise, eat less polyunsaturated fat, right? And get your antioxidants from things like, you know, well-made coffee and from having berries with your yogurt or from eating more, you know, spices like curry when you cook. You know, that that's where I think you create that beautiful mix as opposed to, you know, putting some of that stuff aside and taking pills with X, Y, or Z amounts of a particular antioxidant.

SPEAKER_01 46:23

Yeah, that's great. And it and it really does come back to that blocking and and tackling um the the um and to that amazing list, uh, you know, time restricted eating, you know, 10-hour window, intermittent fasting, uh uh not unlike exercise, though perhaps not of the same magnitude of effect, right? We we do know that as a stress state, fasting will turn on these reduction uh uh systems, regenerative and and repair systems. And so that can be a periodic way uh to get that effect. Um I'm always intrigued by the sauna research, yeah. How time and saunas um and and for those that that like the polarity, you know, the cold plunge, uh the sauna experience, those extremes are stressors, right, on human biology. But when the dose is right, you the benefits are unbelievable. You're again you're turning on these systems.

SPEAKER_00 47:34

So sauna that's an awesome example that because of the heat shock proteins that you generate with that exposure, that that's an awesome example.

SPEAKER_01 47:43

And and we know that it it can mimic many of the same mechanisms, um, health mechanisms as exercise, right? Uh so I I do think when we um look at relatively simple cold exposure, some heat exposure, um right, nutrient-dense foods, move m movement. You know, we know that light and certainly full spectrum light and infrared light in particular, that um comes from the sunshine is a major source of electron flow in in mitochondria and and a great source of energy production. So, again, nothing new here in terms of what we might recommend, but um tying it to these mechanisms hopefully for those um really interested in in these topics can appreciate why it is that these things are so important and why uh what what might seem to be great in a low dose and a high dose um will not will often not have the the intuitive outcome that that one would would predict. And that's the beauty of human biology. And I think that's why the the n equals one that we talk about is so important, John. Uh so much of the research, I think, will fall short in and really um helping uh individuals um translate things into their own lives because that you know the the the designs are set up for sort of black and white kinds of outcomes. You know, you don't see a lot of the the nuance and subtlety that you might see when you make a change in your life, like like cutting out processed vegetable oils or sugar or carbohydrate dense grain-based, you know, flour. And then seeing how you respond to that will be uh the best indicator of where your redux balance is at. Uh you know, you don't have to measure your redux balance uh uh you know to realize uh that something you're doing is either bringing you closer to where you would like to be, or maybe taking you further away from where you'd like to be. So it um our instincts are so sharp when when we create enough uh stillness to allow them to reveal uh whether the path we're on is serving us well or maybe not serving us too well. Um and so that's yeah, this is um there's uh that beautiful sort of uh intuitive sixth sense, right? That spiritual dimension to this, John, that's so important. Um just right in this material scientific reductionist world that we're in, which uh sometimes I think is taking us further away from those uh high finely tuned instinctive um experiences and knowledge that we've acquired.

SPEAKER_00 51:00

Yeah, well said, really well said. I think a lot of times people are being told what to do instead of feeling what's right. And I, you know, I think that with so much of the lifestyle discussion, that's what it comes down to.

SPEAKER_01 51:14

Definitely. Well, good discussion, John. Rich, and um uh I love this and what a joy to be able to uh dive in. Um we will uh we're gonna be looking at a paper that I think will be of real interest uh to folks, uh John, that um uh raises the question of whether is coffee, if you have atrial fibrillation, which is one of the more common heart uh dysrhythmias, uh, is is drinking coffee uh bad for you? And uh that's certainly been, I think, the the clinical meme. We'll take a look at some more recent research challenging that clinical meme. And uh I think um for the coffee lover, this will just be another bit of good news. So I look forward to sharing that next week.

SPEAKER_00 52:04

As do I. Love you, brother.

SPEAKER_01 52:06

Love you too, John. You uh embrace the snow and uh keep uh keep those hormetic effects coming in your life. It it it benefits us all. Uh and I'm grateful for that. And uh, we'll see everyone next week.