Uric Acid, The Hidden Metabolic Signal

A quiet lab number is telling a loud story about modern health. We dig into uric acid as a powerful signal of metabolic strain, connecting the dots between rising sugar intake, sodium overload, dehydration, and that stubborn fatigue and weight gain so many of us feel. Drawing on pioneering research from Richard Johnson and Robert Lustig, we break down how fructose doesn’t just sweeten food; it drains cellular energy, elevates uric acid, and flips an ancient “fat switch” designed for survival. In an era of constant abundance, that switch can stay stuck on, pushing us toward fat storage, brain fog, and cardiometabolic risk.

We question old myths that blame purines and meat for gout while the real drivers—added sugar, processed carbs, and poor hydration—slip by. You’ll hear how high sodium and stress can trigger the body to make fructose internally, layering more uric acid on top of what the diet provides. We also explore the role of acid-base balance, showing why mineral-rich plants and a meaningful alkaline load help kidneys and gut excrete uric acid more effectively. This is practical metabolic literacy: not a lecture on restriction, but a roadmap for rebuilding resilience with smart choices.

Expect clear, actionable steps: test uric acid even without gout; slash added sugars and sweet drinks; hydrate to lower osmolality; train both aerobically and with resistance to revive mitochondria; and rebalance meals with leafy greens, herbs, and root vegetables alongside quality protein. If you’re ready for a deeper reset, strategic low-carb or ketogenic phases can accelerate liver fat loss and insulin sensitivity. We close with mindset: trade judgment for curiosity, and treat each meal and walk as a new lever. If this helps clarify your next step, follow the show, share it with a friend who needs a nudge, and leave a review to help others find these tools.

For slide deck and open source references: www.thehealthedgepodcast.com

Transcript

Setting The Stage: Uric Acid

SPEAKER_01 0:00

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

SPEAKER_00 0:09

Good morning, Mark. And hey, an advanced Happy New Year.

The Metabolic Risk Signal

SPEAKER_01 0:12

Happy New Year to you. We're recording this on New Year's Eve. And uh 2026 is uh bound to be another eventful year and more science, more insights, and undoubtedly a lot more fun topics to discuss as we look ahead, John. But always a joy to connect. And we have another great topic today that I think is uh become more um popular in the sort of wellness functional integrative health circles, John, around uric acid and the importance of uric acid as an uh an epidemiologic trend where we see great increases in uric acid. We appreciate it as a biomarker for metabolic health and all that uh encompasses metabolic health from insulin resistance to hypertension to gout and to all chronic complex diseases, uh, where uh clearly high uric acid uh is a biomarker that uh suggests great risk. And um, and and of course, like like most of the things we discuss, we can look at the changes and trends in the standard American diet and sort of the modern lifestyle as major drivers of these trends. And and then perhaps most importantly, there are so many things that a person can do to better manage uh uric acid and as a consequence improve their metabolic health, their health span or quality of life. And I think we will see more research uh and the longevity and aging uh literature as well in terms of accelerated aging. So it's it's a great topic, John. Um I do want to, if it's okay, John, uh, bring to the to our listeners' attention. You've got a great um Substack uh blog.

SPEAKER_00 2:19

Oh yeah.

SPEAKER_01 2:21

I I which I was recently looking at your overview of this topic, which is just superb, John. Thanks. Um in writing uh that which you do so beautifully well in your teaching. And not, you know, in my experience, uh not a lot of folks can translate in that way. So thank you.

SPEAKER_00 2:42

I appreciate that, Mark. I I really enjoy it. And you know, so much of this uh so much of this is the culmination of working with you for for so many years. So thank you. Right back at you.

SPEAKER_01 2:54

Great stuff. And if people are looking for a really fine, objective, well uh studied subject review, um please check out John's um Substack. Uh and I think it's just John Bagnoula, right?

SPEAKER_00 3:10

If they're on Substack, yeah, that sounds that sounds right. I think so.

SPEAKER_01 3:14

That's an easy one to remember. I'm gonna pull up some slides, John, that we've put together here uh that can help guide this discussion. And again, I apologize for those who are listening and unable to see these, but what um I'll make sure these are on our uh website. And uh hopefully you're seeing that okay, John. Yeah.

SPEAKER_00 3:39

Perfect.

Evolution’s Fat Switch Explained

SPEAKER_01 3:40

And uh I'll so I'll have the slide deck available on our website. And this, of course, can be seen on our YouTube channel as well. And just some uh high-level bullet points as we go through this. Um uh uric acid is rising. These are blood levels of uric acid dramatically in America and around the world, and that trends very uh significantly with what you see epidemiologically in terms of insulin resistance, metabolic syndrome as characterized by insulin resistance, hypertension, large waistlines with visceral fat and fatty liver. Um we're appreciating this more in degenerative neurologic diseases, in particular Alzheimer's, which is getting a lot of interest. Uh mental health, many people don't realize that uh poor metabolic health is highly associated with major depression, bipolar disease, um, post-traumatic stress, uh, OCD. Uh this this, I think, is an enormous area of opportunity when you look at um sort of metabolic uh psychiatry, if you will. And we know that quality of life, of course, uh and aging can be accelerated in uh disrupted metabolic health where uric acid is often very, very high. And as we'll point out, this is another, I think, great example, John, of the importance of looking at the epidemic of chronic complex diseases uh as a consequence of these growing gene environment mismatches. There was a time where having a high uric acid might have been uh an evolutionary advantage. Um and uh um in in a modern context um that that is less the case. And and as we'll point out, uh you begin to see the usual suspects, right, John? Uh it's the high sugar intake, high glycemic carbs, you know, processed carbs, these carbohydrate dense grains, um, fructose, largely from sugar, uh but also from from you know, fructose uh syrup and high fructose concentrated sweeteners, um, alcohol, and uh and in just a huge topic that that we were talking about uh offline and one that we'll dive into a bit more uh in the near future is um uh inability to alkalinize uh the you know the the the metabolic environment as a consequence of the standard American diet. Um and then as we alluded to, there are just many, many things that we can do to improve this, and we will close with that.

SPEAKER_00 6:35

It seemed like a good uh Yeah. I mean, the point, Mark, that you raised here is that this is a many ways, even though hyperuricemia having you know a uric acid level greater than seven um millimoles here per liter, even though that might not be looked at by many healthcare providers as a disease or a condition, when you look at the effects of it, like you just pointed out and how it's tied into insulin resistance and really the metabolic syndrome, you would say it's a pandemic given the prevalence of this now globally. I mean, the the numbers are really just unbelievable. And what I think make those numbers even more profound in terms of the rates of of this as an issue, you know, having high uric acid levels, you know, what I think really stands out is that most people who have hyperuricemia, they're asymptomatic, other than the metabolic issues, right? Which everything gets blamed on, well, your blood sugar levels are okay, we're gonna, you know, we're gonna focus on carbohydrate management, which is a big part of this, don't get me wrong, but that's not that's not it. That's not the only thing that can really correct hyperuricemia. It's how can you help a patient excrete more of this acid? How can you help them with the metabolism of it? And can you make even better choices within the carbohydrate world? We know certain carbohydrates are, you know, you pointed those out. It's not about counting carbs with hyperuricemia. That that might get you part of the way there, but it's about certain types of carbohydrates, especially when they're presented to the liver in combination with other things, like whether it's alcohol or polyunsaturated fat. So I think it's a really fascinating story that it's a global issue. And like you said, it really really illustrates, it really illustrates how you could say this about you more than anybody, could say this about the renal system. We could say this about the hepatobiliary or the liver in general. In a lot of ways, it's like the canary in the coal mine, right? These certain these these organ systems, they give us signs that there's an imbalance. They give us signs that the body is compensating around the clock for that discord between how our ancestors ate and how we ate. For what we're genetically, we have this blueprint to metabolize certain foods in levels, and sometimes those go awry and it prepares us for, like, you know, like you said earlier, a three-week shortage of food. So we're gonna store, right? We're gonna store fat at an accelerated rate. But when we live in the world we do now, the liver can't compensate for some of these imbalances around the clock without their without us taking its toll. And I think uric acid really tells us tells us that story. So I yeah, I think it's a great way to start. I mean, look at the global rates, look at all the imbalances that the liver is faced with and and how it has to adapt to, you know, to the point of fructose. You know, fructose isn't like glucose in terms of what the liver can do with it. It has to, it has to add a phosphorus molecule to it. So when it does that, it's generating uric acid in that situation alone. And then if you already have a high acid burden on the body, it becomes even more difficult to excrete that acid. So it's a it's a fascinating topic. Um, and I yeah, I I love that intro you provided. That's great, giving us the background of that and showing the uh, you know, all the different contributing factors to this.

Fructose, Mitochondria, And Energy Drain

SPEAKER_01 10:16

And we will, we will, uh, this is uh an article that um is a very nice review uh published last year that looks at the sort of global um epidemic of high uric acid and the implication of that. I'll make this, it's an open source article. I'll make this available on our uh healthedgepodcast.com uh website. And some of the slides that we're going to share here, I just wanted to bring this up to our listeners, uh, John, uh, is some research done by, in my view, one of the really fine uh researcher clinicians in the US, Dr. Richard Johnson, who's a nephrologist. He's at the University of Colorado, and uh bridges the lab to the bedside, the bench to the bedside in ways that very few uh uh physicians can these days. And um, I think his work is um uh innovative and uh just I would even say revolutionary. Uh anyone who wants a good review of this um can find it. In his last book, Nature Wants Us to Be Fat, uh, and we'll look we'll look very briefly at that mechanism. Uh what he in a prior book referred to as the the fat switch. Uh and uh that that switch unfortunately is on for most humans that that live on this planet at this time. And from that that article that we just shared, uh this is just a look at the um number of articles uh uh looking at uric acid and the extent to which hyperuricemia has become epidemic uh around the world. And we won't get into the detail of what's on this slide, but there's um historically there have been medications available to lower uric acid, but very, I think, limited insight in terms of what the drivers of this epidemic actually are. And uh, you know, for the nephrologist, this is a fun slide. For most people, this is probably going to give you know cause a migraine. Uh but but the the high-level point of this is that we have systems that that ordinarily allow us to balance um uric acid levels, the amount we produce in our bodies uh and the extent to which we can excrete what we produce uh when that production becomes excessive. And we we know that about a third of uric acid is excreted in our intestinal tract, uh, and about two-thirds are excreted by the kidneys. And this these are just various proteins that enable that excretion in the gut and in the kidneys. And uh the importance of this is that this is a very sophisticated system that allows us to generally handle high uric acid production. Some people might have uh, you know, a genetic predisposition because these systems aren't working quite as well. Uh, but like many complex modern metabolic disorders, this is largely a lifestyle issue. Uh, and and these are medications that have been around a long time. I've prescribed these often that can enhance excretion in the kidney. Uh and many people might also be familiar with allopurinol, uh, which inhibits uh the production of uric acid. So there are good pharmacologic approaches, uh, but you know, who wants to have to rely on that if they can otherwise get to the root cause and mitigate uh that production excretion imbalance? And uh this for me, I think, is one of the one of the fundamental uh aspects for for people to think about, John, and that's this um uh mutation, this uricase that um um you know humans have have lost the uh function of this enzyme, this this protein uricase, which ordinarily breaks down uric acid, you know, preventing those levels from getting too high. And um I'll let you comment on this, John, but but what what we know is that uric acid probably uh for many species had a survival uh uh advantage. Um and and when uric acid was high in times of food scarcity, it really promoted fat storage. This is the fat switch that Richard Johnson referred to. Uh it at times of deprivation uh as uric acid went up and and and often fructose from available fruits uh was was around, uh that mammal could consume it, um uh it would store more fat uh in anticipation of a long winter of deprivation, and that was a survival advantage. But you know, in modern life, uh that that genetic adaptation now becomes maladaptive uh because that um period of deprivation, you know, sort of saving for a rainy day. Uh that rainy day doesn't exist anymore. We just have calories that are abundant, uh, generally of poor quality and readily available.

SPEAKER_00 16:21

Yeah, absolutely. I mean, you have that example in terms of survival because of the effects of elevated uric acid, really promoting more fat deposition and storage. But also, you know, there's examples of where mammals can hibernate because they you know gorge on fructose-rich fruits, right, in the in the autumn or the fall before a long winter, and they're able to, you know, kind of store massive amounts of body fat and then go into that hibernation state. So it's uh it's a metabolic switch, uh, like like many hormones are. And this isn't a hormone as an enzyme, though, but it's a it's a metabolic switch that I think really depicts the the effects of chronic fructose consumption when you when you look at the role that it plays in that, what we do, right? What we do with the with the carbohydrates we eat. I think that's you know, that's a big part of it, really. It's just uh, and I think fructose is high on the radar because of what we know about it. And it's unfortunate because I think for the average person, if they know anything about uric acid or they know anything about gout, they've learned, unfortunately, that it's all about purines and purine metabolism, and you should stay away from things like hard cheeses and sardines. But let's be clear of the you know 25 million people in North America that have hyperuricemia, sardines and hard cheeses are not responsible, right? You could say that high purine uh alcoholic beverages like beer, for instance, could be a contributing factor, but fructose should take center stage. So, right, it can it can become the perfect storm. Um, and then if you put like a high purine load on top of it, yeah, it's only gonna get worse. But to learn that gout, which, you know, again, this is we're going back 50 or 60 years, to learn that gout is a is a disease of excess animal protein is just really misleading. And I think that's what that's what's been portrayed, right? Um, you know, we don't yeah.

Beyond Purines: Rethinking Gout

SPEAKER_01 18:31

Yeah, that that's what I and most of my colleagues have been saying and continue to say for the last few generations, uh, John. It's a very uh uh parochial view of what's really going on. And and when you look at this story, this sort of fat switch story, and again, just I'm just gonna read this, you know, the evolutionary importance of uricase in humans uh centers on its role in that purine metabolism. Purine is like what's in DNA, so um animal uh protein sources are are much higher in in sort of DNA purine content. And uh uh when we lost that uricase uh um activity through evolution, these higher uric acid levels provided a survival edge because it induced insulin resistance, it induced metabolic syndrome for that anticipated seasonal environmental challenge and uh um food scarcity was you you could navigate that by virtue of this metabolic signaling um by enhancing fat storage from largely from fructose because those were the available food sources. Uh now this contributes to obesity, GAT, um it it this Thrifty gene adaptation, right? This being genetically predisposed to store for the rainy day now has become a huge driver of metabolic syndrome and poor health because that rainy day doesn't exist, right? This this thrift trait now has led to fat synthesis year-round. And we know that, as you just pointed out, John, this is really more an issue of sugar, which is the greatest source of fructose in our diet. And what otherwise was a survival edge has now become maladaptive. And this thrifty gene hypothesis, if for those who are interested in the sort of the history of this, it's interesting. This is some of the original uh research. Uh, and the um Dr. James Neal conceived this concept of the thrifty gene in his study of indigenous uh tribes around the world in South America. And so uh it's it's important to keep this in mind. Our modern environments are not well suited to the um uh evolutionary biologic mandate that is alive and well in our in our DNA, in our book of book of life. And so uh this energy storage, right, which we would now call fat, obesity, visceral fat, um these higher uric acid levels just make uh fat storage um more easy and the ability to burn fat much more uh challenging. And we know that other things contribute to this as well, uh particularly um uh the stress, um, which is sort of epidemic in our environment. And uh again, uric acid, which has benefits, um, exerts those benefits when levels are much lower than what we typically see. So, like so much in human biology, right, John? Um not like uric acid is bad, it's a matter of the homeostasis, the balance of production and excretion, uh, which once disrupted, those benefits tend to be lost.

SPEAKER_00 22:22

Yeah, I like that you point out the fact that uric acid does have antioxidant properties. So it, you know, it's again, it's the dose that makes the poison, right? Exactly. It's the dose. And I think modest amounts can, you know, can really offer the body benefits. But when you cross that threshold, it starts to really, again, uh for the modern human, for the modern human, uh, you know, having a uric acid level of four or four point five, it's you know, there there might be some upside to that as opposed to having it at a one or a one point five. But when you cross that that seven, things really start to go downhill fast. And and fruit in in evolution, you I like how you mentioned cooling temperatures around the globe. You know, the ice age brought about the need for a lot of these mechanisms, and I think that's about the time the enzyme disappears.

Sodium, Dehydration, And Endogenous Fructose

SPEAKER_01 23:10

Exactly. Uh, when you start losing fructose in your environment, because you know, fruit-producing um plants can no longer produce uh that's sort of the genius of our metal of our ability to adapt as organisms. Uh uh, and this is just another sort of graphic, uh, a few slides that um from Dr. Richard Johnson. Uh, you know, less fruit available and in during these ice ages, the last of which was probably 10,000, 11,000 uh BC. Um, this Uricase mutation then allows humans to store more fat, to more likely survive these long winter seasons of deprivation. And so um it's a really nice graphical representation of that. And um and fructose is, you know, as you pointed out, John, I think this is really the point of emphasis. Um does appear to be the primary trigger, and again, a lot of this comes from Dr. Johnson, um uh Robert Lustig out at UCSF. Uh, you know, there have been some really great clinical researchers here that have shed light on the devastating effects of sugar and and by extension fructose from sugar in our modern food supplies. And and so fructose, and you pointed this out, John, at the outset, unlike glucose helps produce energy, fructose actually depletes energy because of its requirement of phosphate. So it it withdraws from the energy uh savings account. Uh one can quickly get depletion of one's savings account. Uh and we know that this has very significant effects on the mitochondria. This this um mitochondrial function becomes impaired, and as uric acid goes up, you see more oxidative stress within the mitochondria. And as we we always talk about, John, I think mitochondrial uh disruption uh you know may be one of the great um bullseyes on the target of complex disease. And so you see these mechanisms very much tying to Alzheimer's, to degenerative neurologic diseases, type 2 diabetes as a mitochondrial disease, cardiovascular disease, congestive heart failure, um chronic pain, right? And on and on that list goes. So the the mechanisms here are are really um fascinating and very much aligned with those models. And and then, of course, you know, when one is depleting their energy, the body's well designed to become more hungry. Uh, it'll lower, you know, your metabolic rate will drop because your body wants to conserve. Uh and so uh it's it's really hard to override these signals. If you're trying to lose weight and you're consuming a lot of sugar, fructose, and you know, you're chronically stressed, uh, you know, not not moving very much, uh, all of those ways of more effectively adapting um become lost, and one finds themselves on this slippery slide. And it's you know, as we well know, uh really hard to get off that slippery slide unless you begin to think differently about what's really going on.

SPEAKER_00 26:55

Yeah, and I mean if you look at these four mechanisms uh involved, you know, just to add you mentioned Robert Lustig, who I know, you know, again, and I love Richard Johnson's work. I appreciate you you know highlighting those books and sharing that with me earlier this year. Um but you know, Lustig has found that when you get beyond somewhere for an average adult, when you get beyond 25 grams of fructose for the day, these things start to they start to happen. So you start to shunt energy production away from the mitochondria. So we start burning less fat when you cross that threshold of 25 grams of fructose. So we we start to get more anabolic overall as an organism, right? Storage, prepare for the shortage. And to your point, you know, mitochondrial health and the mitochondrial ability to contribute the majority of our energy, that's central. I mean, that's central to this conversation. And so I just think that that quantity is so boy, in today's foods with today's food choices that most people make, 25 grams happens at a meal, not at a day. Yeah.

Acid Load, Alkaline Balance, And Kidneys

SPEAKER_01 28:15

That's that's such a great point, John, and I and I laugh because uh you've been saying this for as long as I've known you, um, which is many, many, many years, and and yet it's still not uh mainstream thinking uh for the most part. Um when you when you look at this, right, Milo Connor, pretty much all that we've we've touched on, this is a bit just a bit of a summary, but you you see very significant oxidative stress, right, diminished energy production. I mean, who out there uh isn't tired, uh doesn't have the doesn't have the uh energy to really thrive during the day, just completing activities of daily living, let alone uh creating, exercising, um, you know, playing with your kids and grandkids, uh, you know, fatty liver, uh, which as we've talked about in prior recordings, is an epidemic. Uh 25, 30 percent. You we're seeing it in young children. And then, of course, inflammation, you know, one of the great drivers of aging and all diseases, these are all linked, right? It it's a it's a it's a uh the perfect storm. And then, of course, the brain effects, I think, can't be uh can't be overstated, John. Uh even today, um, mental health disease is like a separate bucket, this sort of elusive black box of things that we call depression and bipolar disease, uh OCD, uh it it these I think Many of which are metabolic. These are metabolic disorders. And and I think these are fields that need dramatic transformation in terms of the paradigms that guide how they think and ultimately how one responds. A serotonin uptake inhibitor, worthy though it may be for some people who are in free from a band-aid, um, and is in no way addressing really what's actually going on. Um and this is another sort of summary slide um um from uh Ishimoto's uh research um several years ago, again, just showing that this fructose, and again, largely from sugar, and I think that's you know, we can't overemphasize that sugar is the greatest source of fructose in the American diet. And and when you add uh fruits that are now available year-round that historically were only available seasonally, we talk about eating locally and seasonally, and uh you can get um you know hybridized sugar fructose-rich fruits now that are more abundant and readily available than ever. Uh, obviously high fructose corn syrup, but but but the metabolic storm, the mitochondrial effects, you know, poor oral health, um, leptin resistance, right, fructose as it depletes energy, uh, you don't have the the satiety signal will not work under those circumstances. Because once your brain perceives insufficient energy, uh, even if you're getting more than abundant calories from empty nutritional food sources, uh, your leptin will not work. You will be hungry all the time, you will not move much. Um, Robert Ludwig, another great researcher at the Brigham and Women's, done a lot of this work in children. He's a pediatric uh endocrinologist at the Brigham and Women's Hospital. These guys, in my view, are um uh heroes in this realm of research and bringing the research, applying it, translating it in a way that very much disrupts what has been the um consensus thinking about calories in, calories out. Doesn't matter what the quality of that calorie is.

SPEAKER_00 32:24

It's amazing that still persists, though, isn't it? Yeah. I mean, to me, that's incredible. That's that's like believing the world is flat. It's it's the same, it's at the same level for me.

SPEAKER_01 32:36

Exactly. No question. And and you see just how how uh painfully difficult it is to to change consensus thinking. That's a whole other sort of psychological uh uh phenomenon, and it and it it unintentionally or maybe intentionally hurts a lot of people because it it and I have to say, you know, I've been steeped in academia, as I know you have, John, through the years. Sure academia is is will be one of the more uh uh refractory institutions to change. And um I sadly one cannot look to those expert institutional opinions as uh reflecting what what might be the vanguard um uh science. And uh that you know that's a discussion for another.

SPEAKER_00 33:32

I bet it is, yeah.

SPEAKER_01 33:34

But again, we know these will all contribute to the fat switch, right? Fructose from sugar, from these high glycemic carbs. Um Richard Johnson's research, which I think is particularly um um interesting, in that it adds this additional sort of uh uh contributor, and that is um sodium and dehydration, uh, the extent to which many people just get too much sodium in the in the processed standard American diet, uh, often not enough water. Uh and it's that that higher concentration of sodium uh that, or osmolality, that concentration of the blood, the blood osmolality that uh actually enhances uh fructose production. Um and and so you know, hydration becomes very important in this equation. And then we touch briefly on um alcohol and uh umami, these these savory meats and shellfish, uh beer, you know, those are those can certainly activate uric acid production. Um I would say alcohol is really important just in general from an epidemiologic and health perspective. But as you pointed out, John, these these foods rich in purines are hardly the main issue. It's when you're consuming those in the in the absence of uh more alkaline uh foods and and you know greens and more more sort of plant-based, you know, non-grain uh foods.

Mental Health As Metabolic Health

SPEAKER_00 35:13

Yeah, and that's that's beautiful, Mark, that you weave that in because all of these things can essentially be buffered to some extent by providing the body with more potassium, more calcium, more magnesium, which in chemistry is you're giving the body a greater load of alkaline, right? Alkaline potential substances, things that the body can essentially buffer out not only uric acid, but other acid loads, right? And then it helps compensate for whether it's the high sodium content of the diet, you're able to eliminate that much more freely. You're able to mobilize fluid, thereby, you know, reducing its effect on blood pressure, but at the same time, you're able to clear or excrete more of this uric acid. And so, you know, what I love that you just said is that our ancestors had that alkaline load. It was built in because they weren't eating grains on top of the animal protein. We need the animal protein, we need the nutrients in the animal protein, we need the quality of that protein to maintain lean body mass. And surprising to many, we actually need that animal protein to maintain good bone density. But we need that in conjunction with a much more pH balanced overall diet, right? And we don't get that because people now rely on grains and animal protein, sometimes far, far greater acid loads from the grains and all the cereal products in their diet than the animal protein, which people are again surprised to hear that. They don't realize that the net acid load placed on the body, and we can talk about this in much greater detail later, but it becomes the perfect storm because unlike the Yanamomo that you saw uh Dr. Neil studying in one of your earlier slides, and unlike the, you know, the the new you know, Papua New Guinea, the Highlanders there who are on a chronic, very, very low renal acid load because of all the root vegetables on top of the greens that they're consuming. You know, we're we're having all of this fructose and all of this high sodium loads, we're having that on top of a very, very high potential renal acid load, unlike anything human physiology has ever had to deal with over the course of our history. And so the fructose on top of that, the uric acid on top of that, it's just insurmountable, right? And it's it's it's amazing to me, and I think you could say the same with your your unbelievable background and uh you know, in in renal, in all of the ways that the renal system compensates for the human body's misgivings here. I to me, Mark, what's what's fascinating about this, it's amazing that people are able to walk around and be as functional as they are and in a decent state of health, given all of these discords with our metabolic capacity for some of these things, right? So to think that someone can have you know 50, 60, 75 grams of fructose on top of an acid-loaded diet, right? And to have all of that placed on the liver and on the kidneys and yet still have minimal symptoms other than metabolic syndrome, it's remarkable. And and and I'm saying this in in complete sincerity, it's remarkable that people are as functional as they are given everything their body is challenged with.

SPEAKER_01 38:52

Yeah, hard to uh overstate that, John. Um that yeah, that is a that is a uh profound example of the the human's ability to adapt to a certain point, right? And until you until the proverbial, you know, House of Cards.

SPEAKER_00 39:10

Yeah, House of Cards comes down.

SPEAKER_01 39:12

In the last two minutes, I know you have another commitment, John. Um again, uh it's important to emphasize, and as Dr. Johnson has done in his research and others, researches we've commented on, that while most of the of the fructose we get is external, we do have endogenous sources. Uh glucose can be converted to fructose. Uh this is called the you know the polyol pathway. Uh and as we talked about, excess salt, um, chronic stress, ischemia, you know, people with congestive heart failure or circulatory issues that simply cannot deliver enough oxygen, chronic obstructive lung disease. This will enhance. The internal conversion of glucose to fructose. And if you are on a high glycemic standard American diet, as we've talked about, in addition to these other contributors, you will make fructose on top of what you're consuming. So it really is the perfect storm. And of course, the modern consequences of this we've we've talked about. And this is the really the last slide, John, of just things that people can be thinking about in a way that they can mitigate these metabolic disruptors. And the first advice would be get your uric acid tested, John, because I'm amazed, as I know you are, that much like insulin or a HOMA score, physicians are not inclined to measure a uric acid unless you have symptoms of gout. Or unless maybe you're a kidney stone former as uric acid is in kidney stone. So again, it's that it's that Western model where until you're sick and have a symptom where the red light goes off, there'll be very little interest in tracking a biomarker that has great significance for, as you mentioned, um people who are largely asymptomatic.

SPEAKER_00 41:29

It's not expensive, right, Mark?

Practical Levers To Lower Uric Acid

SPEAKER_01 41:31

No, you're it probably less than$20 to get a uric acid. So it shouldn't be opposition. And again, um, you know, these are just strategies to turn off the switch. And we we've touched on all of these. So by way of reviewing, just trying to obviously limit sugar and these high glycemic um dietary sources, um hydration, obviously very important. Umitochondrial health, and we talk about this all the time. So regular aerobic and resistance activity, you know, sunlight, all of those things. Uh certainly moderating carb to the extent of very low carb ketogenic diets have been shown to be profoundly and rapidly effective in uh reversing these metabolic disruptions. And then, as we'll talk about in the near future, um focusing more on these high alkaline food sources, which are uh ancient ancestors so commonly consumed, uh high in potassium, high in magnesium, high in calcium. Uh, you know, nature has provided us with the with the uh uh the sources uh that we need to um to thrive. And and so um I'll I will stop there, John, and let you close with some comments.

SPEAKER_00 43:06

Yeah, I mean it's a you know I think it's an easy uh it's a real easy component of someone's food choices to to target for some of your greater metabolic returns to get healthier here in 2026. If there's, you know, I I and I don't like to always take the the lens of restriction, avoidance. I I and I know you and I talk about this. Like if if we focus on like make just make sure we get more protein at every meal, you know, I I would say the same thing about what you just mentioned. Let's focus on getting more alkaline-loaded foods. The first time, you know, at first people need to understand what those are, and maybe you and I can talk soon about that um to help them identify those. But there should be some some some good information online for people to look at that. But going back to one of the most important things, even though it's it's good to focus on what we need more of, because that's what our ancestors did as well. They need to they needed to be nourished, and so they chose foods that offered the most nourishment. Um I would say that targeting fructose and saying, you know what, I might not be ready for a ketogenic diet, I might not be ready for a low-carb diet. Because some people, you know, for one reason or another, Mark, I, you know, and I know you found this as well, they're not quite there yet. Uh, and maybe they don't need to be, but the one thing that everybody can do is they can target fructose, they can target added sugars, refined carbohydrates, and still eat a modest amount of carbohydrates from good foods like sweet potatoes and root vegetables, and even potatoes have value at the end of the day compared to, you know, so much of the of the food supply now is 30 to 40 percent refined sugar by weight. And I just think it's you know, it's one of the easiest things for people to target. And for the next year ahead, like really support your health by cutting those things out or reducing them as dramatically as you can and replace them with the foods that our ancestors ate, which are rich in one or more nutrients. And again, I I pick on the white potato a lot because it it has minimal value compared to so many things. But at least it gives you 300 milligrams of potassium, right? At least it's it's not a burden on all of your system. It can raise your blood sugar level, sure. Um, but it's so much better than the carbohydrates that people are you know eating four or five times a day.

SPEAKER_01 45:26

Yeah, that this is a great way to sort of wind down 2025 and to uh uh shine some light on um possibility as as people look to 2026. Uh our lives are about possibility, and um it's it it's important to um uh bring those mindsets into these more sort of scientific um attributes that that we focus on. Uh it's you know, don't forget to love yourself, uh don't don't forget to hang the judgment on the door, love who you are, be forgiving, and see each meal, each step, right? Each new moment is a new opportunity. And that's really uh I I love that the mindset that you inject into that concluding statement there, John. So always a pleasure. Great topic, great discussion.

SPEAKER_00 46:28

I love you, brother. Thanks so much.

SPEAKER_01 46:30

Love you as well, John. Uh happy new year to you, happy new year to our uh our health edge community. Uh check out our website, healthedgepodcast.com. Our podcast is on all the usual sort of media outlets. We do have a YouTube channel uh for those that uh like the visual and want to see these graphics. And again, the PowerPoint will be available on our website. So uh be well, everyone.

SPEAKER_00 46:57

Happy New Year.