Jay Feldman:
 Could a low carb or carnivore diet be the cause of your oxalate problems? We'll be answering that question in today's episode of the Energy Balance Podcast, a podcast where we explore health and nutrition from the bioenergetic view and teach you how to maximize your cellular energy to maximize your health.

In today's episode is part three of our oxalate series, and in this episode we'll be discussing the idea that your kidneys can only clear 50 milligrams of oxalate per day, and whether this has any validity, we'll also discuss whether citrate is effective for clearing oxalates, the impact of low carb and high protein diets on oxalate production and clearance, and how glucose fructose, and insulin affect oxalate production.

As always, to check out these show notes we're linked to the studies, articles, and anything else that we referenced throughout today's episode. Head over to jay feldman wellness.com/podcast and with let's. Alright, so let's talk a little bit about the clearance of oxalates. As we've discussed, we can't metabolically break oxalates down, so once they're produced or once we get them [00:01:00] from our diet, we have to clear them out through the kidneys.

And we've talked about the fact that excessive oxalates beyond our capacity for clearance or, for producing excessive amounts, it does have some negative effects. But also we've been comparing and contrasting a lot of what you hear about oxalates and, this excessive focus on all of the oxalates and food versus what's being produced and the fact that most people are glossing over not recognizing the impact and importance of the metabolic state, especially at the liver and how that impacts oxalate production.

We talked a lot about those things in these last couple episodes, the first two parts of the series, and something that we often hear is that there's a limit to the amount of oxalate that the kidneys can excrete. And we've heard this from especially Sally Norton and some other people who follow her work, that limit is 50 milligrams a day.

And that beyond that, if there's more than 50 milligrams of oxalate that goes beyond the capacity of the kidney to clear it. And then we're going to get deposition of calcium oxalate crystals in the kidney or elsewhere. And so we wanted to touch on that a little bit. For [00:02:00] one, we've talked about a number of things that affect oxalate production and the liver and how much oxalate we might absorb from the diet.

But, it's important to talk about what will affect, how, how well the oxalate is cleared from the kidney and whether the calcium oxalate crystals stay as crystals, whether they could get cleared. So there's a number of things there, but the first thing we want to touch on is just this 50 milligram a day number being the limit for clearance from the kidney.

And the first thing to mention here is I've not seen any evidence at all suggesting that in effect, all the evidence looking at the clearance of oxalates beyond 50 milligrams shows that. Not only is it possible, but it happens to a dramatic extent. And it's really well known that this happens. In people who have primary hyper hyperoxaluria, their urinary excretions are far higher than 50 milligrams.

They're often higher than a hundred milligrams a day. Now, of course, that's not a good thing. We don't want to be exposed internally to massive amounts of oxalate. So not saying there's not a cost there, but the idea that there's this limit at 50 and then, and [00:03:00] anything above that is, is where you start to get an issue from what I've seen, has no basis at all.

And so we'll go through a couple studies here demonstrating that. But is there anything you wanna mention first on that point, Mike? 

Mike Fave:
I just wanna put this in the context, 'cause this goes with the carnivore diet stuff that we're gonna get to later in this episode where the idea is that we have to drastically limit, eliminate or minimize oxalates from the diet as much as possible, which would be further justification for a carnivore diet.

'cause our actual ability to eliminate the ox, the oxalates is minimal. And since we can't metabolize them and you, if you have a hard time excreting them, then basically they store in your tissues and they can store in your tissues for years from your first peanut butter sandwich. I quote from Sally Norton on a podcast. And, but what we're the point here? And just to put this into perspective with the carnivore.

There's a lot of things that affect oxalate absorption from the diet. So I just want to put that out there. Again, calcium intake, magnesium intake type of oxalate present [00:04:00] drastically changes how much you actually absorb and the absorption rates can be really low. If you're at a thousand to 1800 milligrams of calcium per day, or you're magne, you have a, you add supplemental magnesium in the form of maybe like 400 milligrams split in two doses across the day.

You can drastically minimi, minimize intake plus if you shift, if you lower your sources and shift the sources that are not very high in solu oxalates, then you're not gonna have to worry about the absorption of it. So first things first, we're not gonna absorb that much if the diet is set up appropriately, which those things may be hard to do to some extent on a carnivore diet unless you supplement.

And then the next thing that we see here is that the, or what we're getting to here is that the kidney can excrete the oxalates. And you're gonna show this, the study for us today, and you've already, you highlighted this. And so what that means is that the idea that we have to drastically minimize all the oxalate based foods in our diet to the point that it semi justifies a carnivore diet, I think is unfounded, given that the [00:05:00] kidney can excrete quite a bit and absorption is very limited.

So I wanna set that up here. And this is why we're diving into the kinetics and the metabolism or excretion of oxalate at the kidney here. 'cause basically it's the idea is that, oh, you're just accumulating oxalate in your tissues. All of these years, and then you have to like heavily avoid oxalates to get them out.

And I think that what we're going to show, what we're gonna set the stage for here is that's not really the reality of the, or it seems unlikely that is the reality of the circumstance because absorption's not high and based in a lot of factors and we can excrete a decent amount of oxalate on a regular basis.

So I think in the context of carnivore, this is extremely important to set the context, to set things up with, to set the stage here. 

Jay Feldman: Yeah. Yeah, absolutely. Those are great points to consider. And we'll dig into that in a bit more detail. And for now we'll just look at the capacity for the clearance of oxalate from the kidney as a starting place.

And so we're going to look at a couple of studies where the body's introduced to large amounts of oxalates and whether the kidney is actually limited at that 50 milligram mark. So in this first study and the amount of oxalates, I believe was unclear 'cause this was a unique study where they're doing intravenous oxalate injection.

This is a study titled Renal Elimination Kinetics and Plasma Half-Life of Oxalate in Man. And again, this is the next one that we'll get into is looking at massive doses of oxalate, but in this one it gives us an idea of how the clearance. Occurs in the kidney. And so what they state is that the urinary recovery of intravenously injected oxalate was 97.2%, indicating that oxalate is excreted exclusively by the kidney.

The decline of oxalate plasma concentrations followed first order kinetics. So what that means is that the amount of oxalate that's cleared is directly proportional to the amount that that the kidney's basically exposed to the amount that's in the plasma the concentration of oxalate that's in the blood or that was introduced via the IV injected oxalate.

So they didn't find that with this injection there was any limit where it got saturated and there was no there was no longer any further excretion of oxalates. And we see that as well in this study where they used really large doses of oxalates. So I'll just share this one as well since it dovetails right in.

And this is a study titled Dietary Oxalate Loads and Renal Oxalate Handling. And in this study they used doses of two, four, and eight millimoles of oxalate, which is the equivalent of a hundred seventy five, three hundred fifty, and 700 milligrams of oxalate. So this is massive. When we were looking at studies where they set up, a high oxalate diet, it was 250 milligrams.

So here we're talking about nearly three times that in the highest dose and what they basically found was that the rate of oxalate clearance increased with each dose. There was no saturation limit. It wasn't like, it hit a certain point and there was no increased clearance seen in the blood, or sorry in the urine.

There wasn't any max concentration that was hit or anything like that. It continued to increase with the amount of oxalate exposure. And they [00:08:00] comment on that in this quote where they state oxalate is rapidly absorbed and cleared by the kidney by filtration and secretion following an oral oxalate load.

Renal oxalate secretion has a significant role in the renal handling of an oral oxalate load. There's no evidence of acute renal injury or oxidative stress with oral oxalate loads in these experimental conditions, which is pretty notable as well, considering the massive introduction of oxalate here that there was no damage or oxidative stress.

Obviously not like permanent damage, but even signs of an issue. Obviously we're not saying that we wanna go on a 700 milligram a day oxalate diet forever, but it's wasn't acutely an issue here. And as they pointed out, and you see it in the graphs of the study and everything, that there was consistently increased levels of oxalated excretion with each dose.And they look at that as like a permanent basis. 

Mike Fave: Another thing too that's interesting here, if we tie into some of the previous, the episodes that we talked about, where antioxidant status of the tissue is gonna determine whether you actually get that vascular injury. So if you have healthy people who have health like healthy ox antioxidant status, their and their kidneys are functioning well, they'll actually probably be able to excrete the oxalate without any significant issue.

And obviously, again, like this is not saying yeah, go ahead, have a spinach smoothie right now it's just saying that the threshold for the problem is potentially larger than what we're being told. That's the general idea. And the other thing I wanna point out too is that in the previous study that you mentioned, Jay, where they injected intravenous oxalate, they said that the excretion or the urinary recovery was 97.2%, plus or minus 1.4%.

So it could have been up to nine, almost 99% recovery from in, into the urine for of the injected oxalate. And the other thing I wanna mention here is that it is known that there is some secretion of oxalates into the GI tract. So the intestine can get rid of a portion of oxalate as well. So may the large point part is coming from the kidney, but you also get some leaving into the intestine.

So it looks like the body does have mechanisms by which it can actually get rid of oxalates to, to a decent degree without necessarily causing mass injury. Again, this is not a call to say like, all right, just go out, load up on oxalates. But it's a call to say like, how much of the oxalates are actually the problem.

How much of your dietary oxalate or things like this are the issue overall? And can it be, we already talked about mechanisms that they can be, that they can be minimized, at least from the dietary side. And we've discussed some of the metabolic issues. So I think that here what we'd see is this idea that we're just, I think this in general would say that on average in a healthy person.

That the idea that you're just storing tons of oxalates in your tissues is, I think, a little bit questionable because we can see that we can excrete a large portion of the oxalate loads that we're being exposed to on a regular basis. And in the context of other episodes we discussed, you can actually you actually won't absorb a mass amount of de oxalates that you have inside your, from your diet if you have like even a one gram of calcium a day, which really isn't that much calcium overall.

So these are important pieces to take in. The amount that we'd get in a diet probably isn't gonna be that high. 'cause it's just by many factors depending, and it depends on how your diet's set up. And then on top of that, you can excrete what is taken in. So again, like this is starting to put a little bit of a doubt in the, you're just starting to store oxalates across your entire life from your first peanut butter sandwich or whatever the deal is, 

Jay Feldman: right?

Absolutely. And there's a number of other things that affect our capacity for clearing oxalates. That we'll dig into. One of them is the function of the kidneys, of course, and specifically the state of the mitochondria in the kidneys and oxidative stress at the kidneys. We talked about this in terms of effects of the liver and the contribution to oxalate production in the last episode, but it also affects the clearance at the kidneys.

And also we did touch on an on a study in the last episode talking about how oxalates cause more damage at the kidneys when they're when there's a lack of antioxidants. So that's worth noting as well. Now, I do wanna mention, of course, that finding the right diet can have a massive impact on oxalate issues.

And when it comes to creating a diet to optimize metabolic function and reverse or prevent oxalate issues, there's a lot of conflicting information out there, and that's why I've created the Energy Balance Food Guide to help you determine exactly what to eat to optimally support your metabolism and help you lose weight, improve your digestion, get amazing sleep, boost your energy, and so much more.

Energy Balanced Food Guide is a one page infographic that organizes foods on a spectrum based on how effectively they support your metabolism. And it also has a separate spectrum that adjust the scale for you in the case that you're dealing with various digestive issues, which can also contribute to oxalate problems.

The Energy Balanced Food Guide makes it extremely easy to get started with the bioenergetic approach to optimizing your health. So head over to j felman wellness.com/guide to download your free energy balance food guide. All right, so that brings us to the mitochondrial function and oxidative stress at the kidneys, which makes huge differences.

I was saying for calcium clearance and also the deposition of calcium oxalate crystals and the possible damage that they can cause. Mike, do you want to go ahead and share this study detailing that 

Mike Fave: is here? Mitochondrial dysfunction and Kidney stone disease is the title of this paper. What they say is, interestingly, kidney stone disease, nephrolithiasis, or UIs, has been shown to be associated either directly or indirectly with mitochondrial dysfunction.

Previous studies have shown that the pathogenic process of kidney stone disease are associated with oxidative stress condition. There's increasing evidence demonstrating that the tissue injury induced by oxidative stress enhances retention of the causative crystals, especially calcium oxalate inside renal tubules and or kidney interstitium, the parenchyma.

That is one of the crucial steps for kidney stone formation. So essentially what has to happen is the kidney state is going to, to some extent, dictate the stone formation inside the tissue, inside the kidney, inside the tubes that where the blood flows through so that the kidney can actually filter out the blood.

And basically if you have a healthy kidney, if you have a kidney that has adequate antioxidant status, which we already showed in the previous episode, what you find is that the ability to form stones. Particularly calcium oxalate stones is actually drastically decreased. So you have another factor, another pillar here that if your kidneys are functioning well, if kidney health is going and you have adequate antioxidant status, adequate metabolic function, adequate mitochondrial function, then what winds up happening is the damaging effects of calcium oxalate can be drastically minimized.

So not only can you have, you don't have, you can manage how much is coming in from your gut. You can also, you are able to excrete a large portion of the oxalate. And then if your kidneys are healthy, there's a good chance that you can drastically minimize the damage to the kidney with adequate oxidative antioxidant status and mitochondrial function.

And another thing I'd point out here, and this is an extrapolation of my end to be fair, but I would assume that you would see similar things with the vasculature and with other tissues. So if you have healthy tissues, if you have healthy vasculature, the ability of calcium moxley to actually damage that vascular surface.

I think we could be drastically minimized. And the reason I'm saying this, 'cause when you listen to some of the podcasts where, for example, when like Sally Norton is talking about oxalates, there's this idea that, oh, you're just gonna eat the oxalates and like it's just gonna go in and they're just gonna cause massive oxidative stress and they're gonna damage your kidneys and then they're gonna damage your vasculature and they're the cause of everyone's or maybe not everyone's problems, but a lot of people are just getting damaged by ox oxygens all the time and they're storing in your tissues.

And it's maybe not the absorption's probably not that high depending on the dietary context. Then your kidneys can excrete them. So you're probably not gonna see them there for very long. And then if you have a healthy antioxidant status, kidneys are functioning well and the vasculature is healthy, then you're probably not gonna get that much stone formation and damage overall.

So there's a lot of fat. Plus we, there's, we'll get into this, but what's the citrate content of the blood and in of the urine, that's gonna change whether you get stone formation and crystallization as well. So there's a variety of components impacting this beyond just like whether you're having dark chocolate or not.

And I think that's important to point out so that I can eat my dark chocolate in peace. 

Jay Feldman: That's a great point. And yes, also, especially considering, not only the benefits of something like dark chocolate, but potatoes and tons of other foods that have a ton of benefits nutritionally. And yeah, so of course definitely an important one.

And that we don't want to disturb your chocolate eating habit. So with that in mind, let's talk a bit about citrate and citric acid and the impact on calcium oxalate crystals and clearance through the kidney. So a couple things to note. In general, citrate will help to bind with free calcium, which leaves less calcium available to bind with the oxalates, which can help make the oxalates more soluble.

We talked about this in the gut, where if you have oxalates that are more soluble, they're absorbed more easily, and obviously that's not ideal. We want them to be insoluble in the gut, but when we're, when they're in the body, they get cleared more easily if  they're in the soluble form and instead, so we would prefer, sodium oxalate, potassium oxalate instead of calcium oxalate.

Since the calcium oxalate is what tends to cause the crystal formation and causes some issues, but citrate really impressively not only binds with free calcium and prevents it from binding with oxalate, but also has some pretty notable benefits in terms of dissolving the calcium oxalate crystals, which is.

Pretty notable as well. Now, in general, does it, it's worth noting citrate, 'cause it almost sounds random, like you don't really hear citrate talked about very much other than with oxalates. But I just wanted to highlight that in general, citrate is really important for mineral regulations throughout our human physiology and just biology in general.

It helps to prevent excessive crystallization of minerals. So you, we see this in the bone as an example where 6% of the bone weight is actually just citrate. And if you have a lack of citrate there, it actually causes the [00:18:00] bone to be too hard, which then makes it brittle and can make it be susceptible to to fractures and things like that.

So having citrate there maintains some flexibility, prevents success of crystallization. And in addition to all that, it also helps reduce the calcification of soft tissues, of tissues that we don't want to have calcium. So in general, citrate is very important when we're talking about. Mineral maintenance in the body, like maintaining minerals in the right state, and especially calcium in the right state throughout the body.

And that of course comes into play here. Mike, is there anything you wanna mention before we dig into these studies? 

Mike Fave: I just wanted to add here that potassium citrates actually used for people with kidney stones and potentially with hyperoxaluria as a way to prevent stone formation at the kidney because you're basically are supplying a decent amount of citrate without necessarily providing the calcium that would allow for precipitation and to help minimize that stone formation so that's another supplement that somebody could potentially use.

And it's al also an example of something that can be helpful to actually or an example of how citrate can be helpful to prevent the crystallization of oxalate inside the body with calcium or something like this. And this is also why Sally Norton met recommends lemon juice, but there's even a study in PubMed talking about using like orange juice. Bioenergetic to help man to help manage cal calcium oxalate kidney stones, 

Jay Feldman: right? And you might be told to, not consume orange juice because it has some oxalate in there and it has some vitamin C in there, which is a precursor to oxalate. But, and we'll talk about this especially in the last part of this series.

And so with that, let's dig into these couple of studies looking at some of the details of these benefits of citrate and how it has these effects on the calcium oxalate crystals. And so this first study is titled Citrate Non Phosphate can Dissolve Calcium oxalate monohydrate crystals, and detach these crystals from renal tubular cells.

And they state the results showed that citrate not phosphate had significant dissolution effect on calcium oxalate monohydrate crystals as demonstrated by a significant reduction of crystal size. A 37% decrease. Crystal number, approximately 53% decrease in total crystal mass, approximately 72% decrease compared to blank and negative controls.

Moreover, citrate could detach up to 85% of the adherent calcium oxalate monohydrate crystals from renal tubular cell surface. So obviously some, part of this can sound may be a little complicated, but obviously we're seeing some massive numbers here. Large percentage decreases in terms of the calcium oxalate crystals being detached and decreasing in terms of mass and size and number.

So overall something that's really effective at the kidneys for helping to reduce calcium oxalate crystal issues. And so this next study continues on along these same lines and describes this in a bit more detail. The study is titled A non-classical view on calcium oxalate precipitation and the role of citrate.

And they state here we show that citrate interacts with all early stage calcium oxalate species. Poly nuclear stable complexes and amorphous precursors, inhibiting cal calcium ox oxalate nucleation by colloidal stabilization of poly nuclear stable complexes and amorphous calcium oxalate. An interesting paper, basically digging into the details of just direct citrate interaction with the crystals and basically preventing their formation and helping to dissolve those crystals.

Mike Fave: So essentially the takeaway here is that if you have orange juice with some magnesium glycinate and maybe some calcium carbonate, not only can you impair the oxalate absorption significantly, you can also prevent any oxalate that's absorbed to some extent from actually forming crystals altogether. So you have another mechanism here, while the kidney's excreting them in larger amounts than 50 milligrams per day.

Jay Feldman: Exactly. And of course, we produce citrate, endogenously from any like major substrate, glucose and fatty acids can lead to increased citrate production. And that can be utilized as well. But one of the other big factors is the regulation of the citrate, and especially at the kidney whether there's, and in, in the bloodstream too, what's going to regulate and determine whether there's enough citrate kind of passing through.

And so we'll get to that in a moment. But first it's worth talking about bicarbonate as another factor, similar to citrate in terms of something that can help with stone formation and the clearance of calcium oxalate. Do you wanna go ahead and st share this study, Mike? 

Mike Fave: Sure. So the study we have here is titled Current Dietary and Medical Prevention of Renal Calcium Oxalate Stones, and they say Sodium bicarbonate, which is also known as baking soda, has been identified as being able to inhibit stone formation through the alkalization of urine.

Pan Hiro etal found that after the administration of capsule, the sodium bicarbonate is 60 milli equivalents per day. For three days, there was a significant increase in urine, calcium oxalate and urine phosphate. So basically after they gave people the sodium bicarbonate, they saw that people actually excreting the calcium oxalate, and then also phosphate into the urine.

So you have multiple strategies here where citrate and bicarb alkaline substances can have multiple mechanisms by which they actually are helping to increase the excretion of oxalates from the body in the urine. 'cause again, the major site, as we already outlined, is gonna be at the kidney. So we're just, what we're showing is one, you can excrete quite a bit of oxalate on a regular basis, which is great.

It was great news. And then two, there's things that you can use if you are dealing with oxalate issues to actually minimize the stone formation. And some of those things include bicarbonate or sodium bicarb. And then, or it could be cal potentially if it's bicarbonate that's having the effect potentially maybe a calcium carbonate is an option.

Because then the calcium binds up the oxalic acid inside the digestive tract to prevent absorption while also providing a source of bicarb into the blood, such as the bicarb can then help to alkalize the urine and pa help you pass the stones on top of having adequate amounts of citrate present, which again, you can get from, you could take potassium citrate or you can just have some lemon juice.

Or orange juice or things like this that have a decent amount of these organic acids, particularly citrate that can help to inhibit stone formation altogether. So we have now of like just putting the pieces of the puzzle together. We can impair absorption of oxalates. Absorption's already not that high, then we will excrete with our kidneys.

And then on top of that, if our cells and body are healthy, it's, we're gonna have le like a good antioxidant status, good metabolic function, we're less likely to be damaged by the oxalates that are present. And then we can even prevent the crystallization and formation of stones of the oxalates in the bloodstream and also the kidneys using citrate and having adequate bicarbon board.

So a diet that's replete in vitamins and minerals, and then your a healthy body which should be able to actually manage oxalate. And a lot again, like that's in the front face of, not a lot of it's even gonna be absorbed if you have a diet replete in things like calcium and magnesium. So just multiple strategies here where you can actually minimize the negative impacts of oxalates without necessarily going on like a zero oxalate diet.

Jay Feldman: Exactly. And just to come back to a couple of the effects here of the bicarb or calcium carbonate, again, presumably would have a similar effect. But when you have the excretion of more bicarbonate, it makes the urine a bit more basic, not. Actually basic, it still tends to be, below seven pH but at least more on the basic side, which allows for calcium oxalate to become more soluble.

So it helps to clear out the calcium oxalate through that mechanism. It also allows for more citrate excretion, which as we were talking about citrate helps to bind with the calcium and helps to clear it out as well from the kidney. So the, that's a couple of the mechanisms through which the bicarbonate is helpful.

And what that brings us to, which is worth touching on briefly, is general pH balance. And we did have a couple of episodes talking about this in the past, especially in relation to carbon dioxide and so link back to those. But this is important as we're getting at because it affects the solubility of calcium oxalate into urine, which helps to clear it.

It also affects the balance of citrate, which helps to clear the calcium oxalate as well.  And it will come into play when we talk about low carb diets here in a minute, which can sometimes, give the sneak peek that they can interfere with. Optimal pH balance and potentially cause increased calcium oxalate retention and reduced clearance as a result.

So in general, when it comes to the pH balance, we generally want to have a slightly more basic blood pH. And this is something that happens naturally as a byproduct of good functional mitochondrial metabolism. Where if our cells are producing a lot of CO2, especially from glucose metabolism, 'cause fat metabolism produces 50% less CO2 if it's happening at the same rate as glucose, but even less so when you consider that glucose is metabolized at a faster rate, that carbon dioxide that gets produced inside the mitochondria, then leave the mitochondria and the cell as carbonic acid and that carbonic acid binds with calcium and sodium and pulls those outside the cell.

And then when that CO2 leads the body through the lungs, as we breathe it out, we have more calcium and sodium in  the blood, which is better for the cells. You don't want cells that are loaded with calcium and sodium. It's like an cytotoxic state, but also results in having a slightly basic blood pH.

Now this is going to be important because the kidneys are then always managing the blood acid-based balance. And so if we're having a slightly more basic blood pH, it allows for proper function at the kidneys, which we'll get to if the blood instead is more acidic. If we're not having this good metabolic state, we're not pulling the calcium and sodium out from the tissues then the kidneys will respond to that.

They'll adapt to that by retaining more bicarbonate and retaining more citrate in order to maintain a slightly more basic blood pH. And this will then lead to those basically the opposite of what happens when you have, or when you take citrate or when you take bicarbonate, which is the clearance of oxalate.

More solubility of calcium oxalate and more clearance of calcium as well. So when the blood is slightly more acidic, you have basically impaired clearance at the kidneys. When the blood is slightly more basic then you don't have that issue there and you actually have proper clearance through the kidneys.

And in general, on the urine side, as I was saying, we generally want it to be on the basic side, but it's still going to be slightly acidic. And so what they found is that for calcium stone formers, the optimal pH level of the urine is six to 6.5. Any lower than that. And the calcium oxalate is not as soluble and you won't be able to clear it.

But any higher than that, you start to get issues with phosphate where the phosphate the kidney start to retain phosphate and then you can get calcium phosphate stones. Plus we don't wanna be having excess phosphate or phosphorus. That would be the broad overview when it comes to the relationship with blood pH.

And that's gonna come into play in a moment here when we talk about low carp diets. 

Mike Fave: I think the important thing here that you touched on, at least from my perspective, like one of the most important things is that the, if you are oxidizing primarily fatty acids and you decrease the amount of CO2 you have, that's gonna change the  blood alkalinity.

And then that can create a circumstance where you may be more likely to precipitate the calcium oxalate stones and things like this. Because again, you're, because the blood pH has been shifted. And then on top of that, you have effects potentially on blood pH from other components like driving gluconeogenesis ammonia production and things like this.

And also urinary pH that could be shifted through these components. So I think having a this is further pushing towards the idea that having adequate carbohydrate intake to make sure that you are producing adequate amounts of CO2 beyond, just beyond just, the bore haldane effects where you're basically allowing for better tissue oxygenation with more local CO2 production, you're actually getting a better blood pH with the adequate amount of CO2 production, which can help to maintain minerals in their proper forms throughout the body.

So this would be another like perspective here to shift to not necessarily push for the a keto diet or a carnivore diet because you wouldn't have adequate carbohydrates to maintain this. You would've a lower CO2 production [00:30:00] overall at the cellular level because of fatty acid oxidation, which would prevent all these effects that you just mentioned, Jay, with the pulling of the sodium and the calcium into the blood with the carbonic acid from the CO2 production at the cell.

Jay Feldman: Yeah, absolutely. Great points. And as you're saying, we're talking about fatty acid oxidation, favoring that, that's going to come into play here when it comes to low carb diets. Is there anything else you want to add in terms of kidney clearance of oxalates before we talk about the different mechanisms and relationships between oxalates and low carb diets?

Mike Fave: I think the big thing just to before we jump into the low carb diets here, just to set the stage for, is because when we get into low carb diets, we have this idea of the oxalate dumping, right? And so what we want to talk about here is oxalate dumping assumes that you actually will be storing the oxalates that you eat.

At least this theory assumes you'll be storing the oxalates that you eat and over the course of your lifetime, whatever the deal is. And then when you go on this carnivore, low  carb diet, usually carnivore to a large extent, and you don't really have a high amount of oxalates coming in on a regular basis.

And what winds up happening is you just start releasing them from your tissues. But from the beginning here, what we see is that in our first episode, we talked about oxalate absorption is not really that great and on average. And then on top of that, the, if you have certain things in your diet, oxalate, absorption's gonna be even worse.

And in here what we just talked about is oxalates can be excreted pretty easily by a well-functioning kidney. And on top of that, what we just talked about as well, is that if you are metabolizing and you have adequate amounts of things like citrate and adequate amounts of bicarb inside your blood, and also maybe you have adequate calcium coming into the diet, you're gonna prevent the crystallization in stone formation, which is gonna allow for easier passage of oxalates into your urine.

And then on top of this, the other thing to put in perspective here is if the body's state health state is relatively good, antioxidant status is good, metabolic me metabolism is functioning well, then you're gonna be less likely to get stone and crystal deposition at the tissues as well. So basically what we're seeing here is that I think the chance that you have high amounts of oxalate stored in your tissues on the low carb diet that then gets triggered.

When you move into the low, when you move into the low car or carnivore diet that creates all these symptoms, I think the idea that you're even storing the crystals is potentially tenuous for a large amount of people. For the vast majority of people, if you have a primary HOK hyperoxaluria or some other thing like this, or you maybe even juicing spinach for like years on end, we could maybe have a different story.

But I'd say for the vast con, the vast majority of people, the context is probably indicative of not actually having massive amounts of stored oxalates present in tissues, even if you were on a relatively higher oxalate diet. 'cause a lot of these other factors would have to be accounted for. So you would, if you wanted to determine if this was the problem before you went in, you'd have to say, okay, what about this, and this.

To then determine if you actually have this high oxalate load. And so now we're gonna, we'll talk about all the dumping and things like this that happen on the diet, is that actually a thing? But the idea that you're even storing, I think is questionable, which like makes the foundation of the dumping idea questionable.

And then we'll even talk about how the dumping itself is potentially questionable. So I wanted to give the preface here because these components are really important to consider in the context of the oxalate dumping on these low carb diets. 

Jay Feldman: Yeah, absolutely. And there's a number of possible explanations as well, some of which have nothing to do with oxalates.

When it comes to potential symptoms of oxalate issues or oxalate dumping that are pointed to, there's all sorts of other things that could potentially be causing those symptoms. And we know the. Havoc that shifting into a low carb diet can cause in terms of increased stress hormones, and of course the underlying metabolic state stress that the [00:34:00] liver stress, that the kidneys as we'll discuss.

And so if you're dealing with, trouble sleeping or joint pain during that time, there's so many other factors that could be going on that had nothing to do with oxalates. And yeah. So that's something to consider as well. Again, as you're noting it's not a mechanism or like physiological yeah.

Physiological mechanism or like occurrence that's really described anywhere in the literature. It's just an idea that people are using to characterize their state, but there's a lot of other things that I think could be much more likely that's worth considering. 

Mike Fave: Yeah. And will, the thing about this too is so if we can rule out the fact that, which we largely, I think in a lot of contexts we can rule out that there's just like all these stored oxalates inside the body, which we just did, right? 'cause we could show they could be eliminated and we show absorption's not great. So it's like, where are we getting all these stores of oxalates?

And then the next thing that we talk about is like on a carnivore or low carb diet, you don't have them coming in from the diet typically, unless you're like low carb, paleo, keto, eating tons of spinach. But say you're carnivore, right? Which is the main place where you see this. You don't actually have much oxalates coming in 'cause there's no real oxalates and steaks or many of the animal foods.

So you don't have it coming in, but you do have people getting some symptoms. Now some of those symptoms may be caused by other things, which is what you just alluded to, Jay. But then the other piece is maybe some people are having oxalate symptoms, right? Maybe they do have oxalate formation of tissue causing rashes or causing kidney stones or things on these diets.

But the question would then be if the oxalates were already present and stored in the tissues. Why wasn't there symptoms before? Why weren't we seeing the people have these same problems beforehand and then when they, all of a sudden they get released by this low oxalate diet, now they have the problems that timeline, that perspective doesn't make sense.

'cause even if the oxalates aren't in crystal form, we talked about in our first episode that the oxalic  acid itself drives in inflammation, lip peroxidation and damage to the cellular structures and things like this. So you would, if you were already loaded up on oxalates, you would already have these symptoms to a, to the same degree, if not worse.

And when you started dumping them and clearing them through the kidneys, and if anything, like what you would see specifically with oxalate dumping is a worsening potentially of kidney stones because you're dumping it into the kidneys, but they're showing symptoms across the whole body and ascribing it towards oxalate dumping.

So it's unlikely the oxalates are massively accumulating in people's tissues. And then on for the vast majority of cases. And then on top of that, if they did indeed accumulate in tissues, you would probably already have very significant symptoms that were the same, if not worse, than the symptoms you develop when you come onto this diet, this low carb diet.

And then, so it's like that it the hypothesis fundamentally doesn't make too much sense. Like when you start to break things down in this fashion. And that's why we laid out all the metabolic ways this can change. And we're gonna dig into this because I think it's, and I think we agree on this, that what's most likely happens is change in metabolism drives the oxalate dumping syn symptoms, which some may be ascribed to oxalate and others are probably described to other effects of changing metabolism that where people on carnivore and low carb diets are getting these symptoms.

So I would, that's the, I think that's a, that's the context I wanna provide when we go through the rest of these pieces here, because that's like the big thing that you see in a little, oh I'm dumping oxalates, or I need to go on a carnivore diet to just dump the oxalates. So that would, yeah, I wanted to set that up before we jump in.

Jay Feldman: And not to mention as you're, as we're going to get into, there is the possibility that oxalates are involved here, but it might just be increased endogenous production and impaired clearance of oxalates. And again if the notion is that this is supposed to be a diet, like if the idea is that you've shifted to a better diet, which should be lowering oxidative stress, lowering lipid peroxidation, all of those things, those are all of the things that not only lead to  oxalate production.

So you should hypothetically have much less, but also allow for proper clearance of those oxalates. So if you're getting oxalate symptoms, that those two things don't align because you should be able to really effectively clear oxalates if. You're in a generally good metabolic state without excessive oxidative stress and all of that, as we just talked about when it comes to kidney clearance and mitochondrial dysfunction there, and we've talked about it prior with lipid oxidation and antioxidants, protecting against the effects of oxalates.

If you shifted to a better diet, you should be having fewer oxalate symptoms, not more, 

Mike Fave: and you wouldn't have a long time course and a fluctuating time course with oxalates, right? Because how much would you actually have stored in your tissues to be releasing and what, why would the time course be fluctuating over time?

These types of things I don't think are like well explained by the theory. So something to keep in mind is it is a theory. We're just like, we're just questioning the specific theory. It's not a shot at Sally or anybody else who's making the theory is about the theory itself. And then on top of  that, it's like there's some holes with the theory.

And the question is, why is this happening? And that's a very important question because if it's just your dumping oxalates, then you can argue that's a potentially a good thing. But if it's actually because you're increasing endogenous production of oxalates when you're on this diet, then that's actually a bad thing and potentially worse.

So that's why it's very important to okay, we have a theory. Is this the reality or is there other explanations? And if the other explanations are opposite, then you need to really be careful of what you're like, what you're doing with this hypothesis is oh, I'm just dumping all the oli that I stored up.

Or, oh, I'm actually increasing my endogenous production of oxalates pretty significantly to the point that I drive symptoms while I'm on my, on this diet, while I'm thinking that I'm depleting myself oxalates, I'm actually worsening it in the long run potentially, or the symptoms are caused by something else and I'm ascribing it to oxalates.

So we really wanna be clear on what this is, that we're not even saying that we know the exact theory or the exact reason why people  are getting this. We're just saying that the original theory is problematic. But for multiple reasons, especially in light of all the research that we just brought to, we just discussed on oxalates.

And then on top of that, there's a variety of other theories that could explain this, that are counter to the discussion of the of the, you're just storing oxalates, like this initial theory. And if that's the case, then that is a huge problem because people are doing, are going on carnivore diets to some extent to avoid oxalates and avoid these problems.

But if endogenous synthesis is ramping up to create problems, now we have a huge, now we have a huge discrepancy that would need to be rectified. So that's something that's I think really important for anybody who's doing these diets to try to lower their oxalate load or something like this to be clear on what is actually happening so you can make sure you're actually going for the effect that you're shooting for instead of being enga engaging in something that could be potentially making you worse.

And you're the theory that you're thinking is going on isn't actually what's going on. 

Jay Feldman: Yeah. Yeah. Absolutely. And, I did wanna highlight  two other things, which we're gonna dig into each of these three now. But in addition to increased endogenous oxalate production occurring in the low carb diet, there's also the potential for increased oxalate absorption and reduced oxalate clearance.

And so those things together could be causing oxalate issues rather than it being a good thing, as you're saying, where you're just clearing oxalates and this is great and let's keep it going. Yeah, an important distinction and let's dig into some of the potential evidence there that points in that direction.

And so the first one being in terms of oxalate absorption. And so first thing I want to touch on, and we've touched on this, in the first episode, which is that the less oxalate we consume, the greater proportion we absorb. So the difference between consuming a very low oxalate and a very high oxalate diet isn't that big or anywhere near as big as you would think when it comes to looking at the actual milligrams of oxalate absorbed.

And so we looked at this study earlier as titled. Or it's titled contribution of dietary oxalate to urinary oxalate excretion. And they have this figure where they show that with a very low oxalate diet of 10 milligrams, 55.4% gets absorbed. Whereas on the very high 250 milligram diet, 5.8% was absorbed.

And we did see other studies showing lower percentages with higher calcium intake. So in this case, sure we might have a very low oxalate diet, but we would've much greater absorption. So in this case, assuming all else equal, the difference between the 10 milligram per 10 milligram oxalate diet versus the 250 milligram oxalate diet, when you consider absorption, there's only a difference of around nine milligrams.

'cause it's five and a half milligrams absorbed on the low oxalate diet, and 14 and a half absorbed on the high oxalate diet. So yes, you've drastically lowered your oxalate intake, but because you've absorbed so much more percentage wise, proportion wise, it might only have reduced your oxalate exposure in that regard by about nine milligrams.

Let's take into account a couple other things that often happen on these low carb diets. One of them is low calcium intake. Typically, there's very little calcium source in this diet. Typically, dairy is not included, but obviously there's different  variations of low carb and all of that. But it's worth noting that when it comes to dairy butter and gh, those aren't going to have any calcium and, sources.

And when it comes to, sometimes people think like bone broth would be a good source of calcium, but it's actually not. You don't actually when you create broth, it doesn't actually pull the calcium out from the bone. So you're not getting really any calcium from your diet here unless you're including calcium rich sources of dairy or leafy greens that have a considerable amount of calcium.

And so the vast majority of people on these low carb diets and obviously we see this all the time, are consuming very low amounts of calcium. And we talked about this earlier, how dramatically that increases oxalate absorption. So those are two major reasons why you could see. Not that much different amount of oxalate coming in from the diet, which again, also comes into question in terms of this oxalate dumping.

It's one thing if you were like, before you were getting 50 milligrams a day of oxalate being absorbed through the gut and now you're getting three. Yes. Maybe that could point in that direction. Again, I think there's other reasons that point away from it. But ALS  also, that's probably not the case.

The difference in actual oxalate coming into the body from the gut is probably not that big considering those two points. One other point I wanna mention here, and then I'll let you touch on the fat digestion piece, Mike is that when we have a lack of calcium and when we have a high phosphorus intake, which when you're eating a lot of meat, you're going to have a lot of phosphorus intake as well, which is typical on low carbon keto diets.

It then leads to increased parathyroid hormone production, which also leads to increased 1 25 dye hydroxy Vitamin D production. And we talked about this in that first oxalate episode, but this also increases oxalate absorption. So we have a third reason here why you're going to see increased oxalate absorption, even from the smaller amount that's coming out of the diet.

Mike Fave: The other thing I wanna point out with this and I'll get into the fat digestion. So a couple pieces. First thing, if you think you're getting a bunch of calcium and you're taking in a bunch of bone broth to solve this problem, you're actually taking in a bunch of hydroxyproline, which we talked about is a good source for endogenous oxalate synthesis.

So that's one thing, especially in the context of a carnivore diet and how it changed  metabolism. But we'll jump into that into the next section. So I don't wanna get too far ahead. But the other thing I wanna point out is the oxalate dumping hypothesis says that if you have a little bit of oxalate, like a food that has a little bit of oxalate, it will actually help to minimize your oxalate symptoms.

Now, I don't know if this is actually the case, and maybe it is. I haven't tested it out myself 'cause I haven't had oxalate dumping symptoms even when I was low-carb. However, what I will say is that say you have just a small amount, like a square or a small square of dark chocolate or something like this, and.

You assume the absorption, say the absorption of the oxalate does increase quite a bit, right? The amount of oxalate that you're gonna take in from a SM square of dark chocolate is not gonna be that large. And the absorption is gonna be like, even if it's slightly increased from the carnivore diet, it's still gonna be relatively low.

And so then the question is like how much are you actually increasing the serum oxalate levels when you taking this very small amount of oxalate? And is that is that really a threshold enough versus your endogenous synthesis to actually change the amount of oxalate that you're seeing going, like for your tissues especially?

'cause again, like if endogenous synthesis is drastically ramping up, which we're gonna talk about here, I think it's doubtful that adding an extra even five. Milligrams of oxalate coming in from your diet when you have however much being produced from your body in this state, is actually gonna massively change the signaling of that thing.

'cause again, absorption is not that high and the recommendation is not to take in a massive amount of oxalate. It's to take in a small amount of oxalate, which again puts. Puts the oxalate dumping hypothesis situation on puts it a little bit in question as far as if you just don't have oxalates and your body says, Hey, we're gonna just stop dump, we're gonna start dumping all these oxalates and get free free the tissues of them.

And then if you have a little bit, that tells your body, oh, you can't dump them anymore. I feel like that hypothesis with these mechanisms in mind doesn't really play out very well. It doesn't really hold, its, it, its salt here holds its weight here. With these factors in mind, the rate of the,  how much oxalates absorbed on a regular basis and how much somebody's actually taking in as far as their little bit of oxalate to try to reverse the process.

And again, it's so say you have 50 milligrams of production per day. It's okay, so you add three or you have five. Is that really that much? A percentage of the total that's gonna make a massive shift in the signaling. Those are things we need to, I'm not saying I even know that answer. I'm just saying I think it's less likely that would be the case and we would actually have to see that play out instead of just like having this theory and not having it actually tested or proven.

So again, like that's another question that I have or another te a pillar of this theory that I'm like, yeah, I don't know if that really holds that much water for me, as well as the like storing in tissues and dumping. So it's another piece I wanted to add, but the last thing I wanted to say here is that if you are on a carnivore diet or a, like a really high fat.

Diet, like a keto diet, and you are having issues digesting all the fat, you're dumping more fat into your colon on a regular basis. What's gonna wind up happening is that fat is gonna mix with calcium [00:48:00] inside the intestine form calcium salts, which is gonna impair your ability to actually bind that calcium to the oxalate in the intestine and then and minimizes absorption.

So it's another way that you could actually maybe enhance the absorption of oxalates a bit on a diet. But again, with minimal amount of oxalates coming in on the diet, it's probably less of a concern. But it is a reason why some of these types of diets could potentially worsen the, or enhance the absorption of the oxalates overall.

'cause the lack of calcium, the shift in PTH signaling and potentially fat maldigestion depending on the individual's context overall. But I would say, I would still say with that oxalate, total oxalate intake on a carnivore diet is gonna be like barely anything. So the most of the oxalate has to come.

From endogenous sources on a regular basis until somebody proves that these people are just completely overloaded with oxalates and they're just dumping them, I would say it's we'll get into to endogenous. It seems like it's mostly endogenous. 

Jay Feldman: Yeah. There's a number of  reasons why endogenous production would be increased.

And as you were saying, it was an interesting point to consider, which is that if, even if things are functioning normally and you're producing, let's say 25 milligrams of oxalate and you were to eat something that just had a few milligrams, that you're not really moving the needle there. Why would that cause some sudden change in oxalate metabolism or clearance from the tissues and all of that?

Yeah, an interesting point and yeah. So the first consideration here is just despite a much lower oxalate intake, we would have dramatically 10 plus times, probably even as much as 20 times higher oxalate absorption. So the amount of absorption from the gut, the total amount of oxalate coming in from the diet might not be as big as is thought considering the massive change in oxalate absorption.

But as you've been getting at, I think the bigger factor here, or at least the a factor that's bigger. I also think clearance is a big one, but bigger factor here would be oxalate production. And there's a number of reasons why you might see increased oxalate production on a low carb and especially carnivore diet.

One that you touched on  is hydroxyproline intake. So as we talked about before, hydroxyproline is a precursor to oxalate. And normally it's a pretty small one, but there are studies that show when you increase the amount of hydroxyproline consumed, it does increase oxalate production and clearance. And obviously if you're eating a ton more muscle meat, especially ground meat meats that have more connective tissue, which are generally beneficial, we're not saying that you should avoid gelatin, oralus tissue or anything like that.

But especially in a state like this, that's going to be a contributing factor here where you're increasing the precursor, one of the main precursors to your own oxalate production. So that would be the first point here to consider. 

Mike Fave: And there's a study in humans using gelatin to increase glyoxal and oxalate excretion and glycol excretion in humans' urine.

So it, if you have a circumstance where you're taking it a bunch more precursor, like a carnivore diet, people could be between two and 400 grams of protein a day and maybe higher depending on what they're doing. I have, the reason I know is I have clients who've done carnivore diets and I've seen their diets with listed out on  chronometer, and I've seen their protein intakes.

And basically if you have that high of a protein intake from animal sources and you're doing bone broth and gelatin and collagen and things that are recommended in these spheres, you're gonna have a high hydroxyproline intake. And if you have that on top of an increased production at the tissue, at the liver because of the change in metabolism, which we'll get into, then you could probably see an enhanced production of gly, oxalate and oxalate in that circumstance.

So that's something I think is important. So we've seen this, there's human studies showing this with people taking in 10, 20, 30 grams of gelatin. You see an increase in oxalate excretion. 

Jay Feldman: Yeah. And again, if everything's functioning well, not a major concern, but it certainly adds on here. Which brings us to a couple of other factors that would likely be increasing the amount of oxalate produced endogenously.

The first one being that methyl glyoxal has been shown to increase on low carb diets. There's studies showing this on an Atkins style diet where there's dramatic increases in methyl glyoxal. And the reason for this is because one of the  ketones that's produced is called acetone, and it's a direct precursor to methyl glyoxal.

And as we talked about in the last episode, one of the main enzymes, or one of the more important enzymes here to reduce gly oxalate production, which is one of the main precursors to oxalate, is gly oxalate, which converts glyoxal to glycosate instead of gly oxalate. And methylene gly or methyl glyoxal compete for, with glyoxal for glyoxal activity, they both use that same enzyme.

And so when you have increased methyl glyoxal using that enzyme, it leaves less available to convert the glyoxal into glycol. And so that can be another potential driver of oxalate production in terms of increasing the amount of gly oxalate that's available to be converted to oxalate. 

Mike Fave: Yeah. Yeah. I don't have too much to add to that besides the fact that it's just interesting seeing that ages, like people ascribe ages to carbohydrate.

But on a keto diet, the ketone production process drastically increases the age, the advanced glycation end products through methyl glyoxal. And basically you're just saying that the methyl glyoxal here is gonna impair the ability of glyoxal to be converted into glycol. So it gets shifted towards gly oxalate, which can shift it further with the glyoxal can be converted further into oxalate.

So you're just changing metabolism towards oxalate. 

Jay Feldman: Exactly. And so those are two, two factors here. But I would say the largest one would be the increase in gluconeogenesis and increase in glucagon that occurs on a low carb diet. We talked a little bit about this in the last episode. Mike, do you wanna dig into this study that we talked about?

We'll just kinda review. There's no need to actually really share any quotes from the study. So we talked about it last time, but there was a couple of clear mechanisms that they described that increase oxalate production when gluconeogenesis is going on under the influence of glucagon.

Mike Fave: Yeah. So basically what we saw is that the main enzyme that can take gly oxalate, which is the major precursor to oxalate and convert it to glycine, is a GXT one. And essentially what happens is if [00:54:00] you, the a gxt one enzyme requires pyruvate and alanine to function appropriately. And when you push the gluconeogenesis, what happens is you actually deplete.

Your alanine and your pyruvate levels. And what that does is it impairs the ag XT one's function so that you can't then convert the gly oxalate into glycine, and you get stuck with gly oxalate and the gly oxalate. It's like, all right I'm not gonna a glycine, so I might as well go over to oxalate.

And so then you get a higher amount of oxalate through there. And then on top of that, the gluconeogenesis depletes when it depletes pyruvate, which is a substrate for lactase dehydrogenase, lactase de dehydrogenase, the enzyme gets a little bit lonely. And it starts to say, all right if I don't have my pyruvate, I guess we're just gonna have to get some gly oxalate.

And so it gets glyoxal, and then it can take the oxalate and turn it into oxalate. So basically you're setting the stage here. Where you can have an increase in the production of oxalate by driving gluconeogenesis heavily. And why is this important on a cardboard diet? 'cause you have a high protein, like zero carbohydrate diet to some extent are very low carbohydrate diet.

The same thing with keto, although the keto would arguably be less problematic from this standpoint because keto tends to control protein levels to avoid excessive gluconeogenesis. Whereas the carnivore diet, like it's just gluconeogenesis, to the lay the out, no, no hold bars, like it's just gluconeogenesis to the max.

However you set up the diet, have your steak, whatever the deal is, which would make this worse because you have very high protein intake, you're driving gluconeogenesis and then you're shifting the metabolism in this direction. And imagine like you have a lot of hydroxyproline and a lot of gluconeogenesis going on.

So even if the hydroxyproline can increases things a percentage, but then you're increasing the conversion. Like now you have a percentage mult, like on a percentage increase. In these states. So I think it the reason why you may see small amounts individually versus when you see maybe a larger increase to the point that it gives somebody  symptoms when you have multiples.

'cause there's potentially some synergism here where you have an increased precursor with increased pre conversion towards oxley, which is okay, now you're really pushing the envelope. 

Jay Feldman: Yeah, absolutely. And those things together leading to potentially massive increases in oxalate, especially early on.

So if this, the idea is that this oxalate dumping is something that you notice, especially early on, that's when you're going to have the greatest increases in glucagon, adrenalin, and cortisol. The greatest increases in gluconeogenesis, 'cause your body is still using a lot of carbohydrate and is shifting into using more fat and ketones.

Now, even in a chronic basis on a low carb keto diet, you'll still have elevated glucagon and gluconeogenesis compared to a carbohydrate. Including diet. So you will still have increases in these mechanisms on a carnivore type diet. You're going to have even more increases in these mechanisms because of further reliance on gluconeogenesis from protein to produce glucose.

And you tend to use a lot more glucose from the protein that's being consumed on a carnivore diet. So you'd have this to an even greater extent. And then there's a couple other mechanisms they touch on in that paper. We went over it in that last study. But yeah, just worth mentioning on one hand because you have a depletion in pyruvate and lactate since they're being used to be as precursors for glucose.

That increases the lactate dehydrogenase activity, as you said, in terms of converting the glyoxal to oxalate. But then you also have the fact that lactate interferes with or reduces the activity of glyco eight oxidase, which con converts glycol into gly oxalate. But when lactate is reduced, that frees up that enzyme and increases the conversion of glycol to glyoxal, which then of course will increase further to oxalate.

So a couple of different, three different mechanisms really that can be responsible for an increase in oxalate production just from the excess glucagon and gluconeogenesis, which brings us to some other effects of protein intake in terms of ate production and the clearance from the kidney Considering.

Just, and again, this is not gonna apply as much  to restrict keto diet, which is of course lower on protein. But when we're talking about a carnivore based diet where there's especially higher protein, there are some extra concerns here in terms of oxalates. So that brings us to one of the next possible drivers of increased oxalate production on a carnivore diet especially, or on a low carb diet where a lot of protein is consumed.

And that is the amount of protein intake. And there can be a couple reasons for this. Most of which center around excess protein driving gluconeogenesis as we discussed. And also the fact that the protein tends to contain higher amounts of hydroxyproline, which of course can be a precursor to, to oxalate.

And so there are a couple studies supporting this. I will say the research here, there is some, it does conflict a little bit. There are a number of studies also suggesting that protein intake, in reasonable amounts doesn't actually increase oxalate production. And of course we would agree with that, but I think instead this research just points again, to further support that excess amounts of protein intake can be an issue in terms of [00:59:00] oxalate production and can be an issue in terms of kidney function too, which is also something that we've discussed in the past.

But we'll just start out here. By digging into this first study, which is titled Relationship of Protein Intake to Urinary Oxalate and Glycol Excretion, and they state on cell selected diets, no correlation was detected between protein intake and urinary oxalate or glycol excretion. However, on controlled protein diets, females excreted 20% more oxalate on a high protein diet.

This was 1.8 grams of protein per kilogram of body weight compared to a low protein diet of 0.6 grams per kilogram of body weight. No difference was observed in males glycol eight excretion was significantly higher on the high protein diet compared to the low protein diet in both sexes. And so what that does tell us what the higher glycol excretion is, that if the protein were increased a little higher for the men, perhaps we would've started to see some increase in oxalate production as well.

Again, this is, these aren't, this is not an excessively high protein diet. 1.8 grams per kilogram  and 20% more oxalate isn't a. Necessarily excessive either. And this again, doesn't mean that if you consume that amount of protein, you'll automatically have increased oxalate excretion. But again, it does just point to something that we wanna consider, which is the excess protein intake that especially happens on, low carb diets where somebody is not particularly focused on being in a ketogenic state, especially the carnivore type diets which could drive excess oxalate production.

Mike Fave: Yeah, I think for me, when I see this, the biggest takeaway is the, when you put this into the full contextual picture of a carnivore diet or a diet such as a carnivore diet, you have this circumstance. We have a really high protein intake, or most likely have an exceptionally high protein intake. On top of a very low carbohydrate intake, which we've discussed and we'll get into further as ways to actually upregulate oxalate production.

And so the increased protein intake, plus the increased gluconeogenesis, plus the higher hydroxyproline content, especially if you have a collagen or a gelatin present and then potentially adjustments to calcium intake and things like this, and maybe citrate intake, I think leads to a circumstance where you're just pushing the entire needle over towards the oxalate production side, towards the endogenous oxalate production side.

So I think this is just another, brick in the wall showing that okay, in this context where we have low carbohydrate intake, really high protein intake on the carnivore diet, the upregulated gluconeogenesis, the lack of calcium intake, potentially lack of citrate intake, these components driving the system towards that oxalate production.

And so I think it's, in normal circumstances, probably not an issue. But with this full conglomeration of components put together, likely shifting the needle towards a higher oxalate production and on somebody who has a predisposition towards having oxalate issues. I think this is where you can see the precipitation of the oxalate dumping, or you see the people on these cardboard diets getting these oxalate symptoms.

I think it is related to the, a variety of these factors coming together. So it's not  the one thing by itself, it's the multiple pieces synergizing to create that effect. 

Jay Feldman: Yeah, absolutely. And again, the assumption here built in would be that especially if that protein is coming at the cost of carbohydrate intake, you're going to see this to an even greater extent.

Mike, do you wanna go ahead and share this study where they discussed that? 

Mike Fave: Sure. So the next study that we have here is titled Effect of Low Carbohydrate, high Protein Diets on acid-based balance, stone forming Propensity and Calcium Metabolism. What they say, or the quote from this paper says, consumption of a low carb high protein diet for six weeks delivers a marked acid load to the kidney.

Increase the, increases the risk for stone formation, decreases estimated calcium balance, and may increase the risk for bone loss. So basically, when you take individuals and you put them on a lower carbohydrate, high protein feeding, they did this for six week, what they saw was that the amount of acid, so that there's, it's not just like pure acid, but different components that would increase the acidity of the blood is increased.

And then that decreases alkalinity, which adjusts the acid-based balance of the kidney, which will increase the risk for the formation of kidney stones. Arguably those could be oxalate kidney stones. Then you also have decreased calcium balance overall in this diet, likely because number one, less calcium is probably coming in based on the food selection.

And then number two, because you have a higher amount of acid load from the amino acids from the protein. And then essentially they say, we're saying this could be an increased risk for bone loss. Maybe it, it's probably not just because of the protein intake that this occurred, but maybe how the diet was set up overall.

So another circumstance where you're seeing that if you lower the carb and then you have the higher protein intake, you shift towards a higher protein intake, you are increasing the propensity towards stone formation, which in conjunction with the other factors that we discussed, the gluconeogenesis, the change in oxidative state, the change in thymine status, citrate intake, things like this on top is on top of the increased hydroxyproline intake can further push pe an individual who's running a very low carbohydrate high protein diet towards oxalate production.

Jay Feldman:  Yeah, exactly. And as we discussed in terms of acid-based balance, it's not just the acidity of the proteins, but also especially on a low carb diet, we have the shift toward fatty acid oxidation, meaning less CO2 production, and that being a major driver of the acidic state as well. And then you also have the byproducts of excess protein consumption like ammonia.

And also on a low carb diet, especially if the ketones product, the ketone production and ketones themselves are acidic too. So a number of different factors there that could all contribute to increased oxalate production at the liver. And then we'll also talk about the potential impact of what's going on at the kidneys.

But that brings us to something else that's worth highlighting here, which is the importance of glucose and carbohydrate as well as insulin for oxidative stress. And there are some, again, despite what's often being told that what we are often told, or many of you are often told, which is that increased carbohydrate consumption drives oxidative stress.

The reality is that glucose and insulin especially, are  incredibly important for opposing oxidative stress. And there's a number of different mechanisms here that we're just going to broadly touch on and all cite, the studies in the show notes as always. But, getting into the details is a little bit outside the scope.

Of this episode, but the short of it is that glucose is a primary driver through what's called a pentose phosphate pathway. And that pathway helps to regenerate N-A-D-P-H and reduced glutathione which are necessary for basically antioxidant effects. And you see basically a tag team going on with insulin, where insulin has direct effects on glutathione production and direct effects in terms of increasing glyoxal release expression.

And so we talked about this, in the last episode when we discussed some of the different enzymes that are involved in oxalate production at the liver, and also the influence of oxidate of stress, which has been shown to increase oxalate production. And so glucose and insulin here help to directly oppose that oxidative stress and help to reduce oxalate production.

And they help with, as I mentioned, the glyoxal enzyme where insulin has a direct effect  there which will help reduce glyoxal production. And then it also helps with glyoxal reductase activity. And so in that regard and that's again, more independent but, or a more independent mechanism as opposed to, or indirect mechanism I should say.

Whereas the insulin affecting galal is direct. But between the regenerated N-A-D-P-H and the reduced glutathione, those help support the oxalate reductase activity. And that helps to also lower glyoxal. So we have a couple of important mechanisms here by which if you are avoiding carbohydrates and you're avoiding insulin, you'll actually have potentially increased oxidative stress.

And that can also be a mechanism that would drive increased oxalate production. 

Mike Fave: Yeah, I think other things to add here that would be important to consider as well. Is that the oxidation of glucose in the mitochondria also produces less reactive oxygen species, of course. So not only is glucose running through the pento phosphate pathway increasing the amount of glutathione that we have, which is the master antioxidant in the body,  it's also decreasing ROS production by shifting what's going on inside the electron transport chain in complex one, complex two, and co-enzyme q.

So there's multiple mechanisms, whereas optimal or adequate glucose oxidation is allowing for decreased oxidative stress overall. And I think the other thing just to, I wanted to clear up really quick here based on what you said, Jay, but the insulin increasing gly oxalate expression allows us to take the gly oxalate and turn it into glycol instead of having it go towards oxalate.

So it's actually shifting, having the car iry present is shifting glyoxal away from oxalate and towards glycol. So the. You have this. And the glutathione is also important 'cause it's involved directly in these processes. So we need to have adequate antioxidant status by producing glutathione. And we also don't want to have a high oxidative burden that will use up glutathione.

So having adequate carbohydrate and oxidizing that carbohydrate appropriately allows us to minimize the oxidative stress production. So we [01:08:00] don't have to use up as much glutathione and allows us to produce more glutathione. So we have a net higher level of glutathione, which is needed to take gly oxalate and convert it to glycol through the gly oxalate en glyoxal enzyme.

So there's multiple steps here where adequate GT glucose oxidation is actually improving the ability of us to take oxalate away from oxalate to, to not turn it into that oxalate. So is another thing, another circumstance we're seeing you, the carbohydrate is actually beneficial here. And I just wanna make a brief mention here that.

'cause people are gonna say glucose causes the ages anyway. And we were already talking about glyoxal. But it's not that glucose causes these problems. It's that impaired mitochondrial and energetic production or function at the cell leads to a backlog of glucose that then leads to the formation of advanced glycation end products.

So the problem isn't the carbohydrate by itself, the problem is the mitochondrial dysfunction and then the downstream of, or I guess up the, depending on how you look at the picture, the upstream, downstream effects of that or see the effects.  The consequences of that then lead to the, then lead to issues with advanced glycation end products.

But it's not glucose by itself, it's the dysfunction that caused the issue. You should be able to oxidize the glucose all the way through. And that's what we're looking for. 'cause ultimately that is the optimal circumstance. That is the ideal circumstance is the glucose oxidizing fruit through allowing for the decreased r os in the mitochondria re restoring or not using up our glutathione.

The glucose being used in a pentose phosphate pathway produce any DPH to recycle glutathione. And that all helps in the context of oxalate, helps us to shift the glyoxal away from oxalate towards the glycol so that we can, we don't have a lot of oxalate going into the system on top of all the other benefits that we've talked about with adequate glucose oxidation in this circumstance.

So it's like it all fits together in one nice picture when you start to see these different shifts or you start to see the different I guess broad swaths or trends with having adequate amount of glucose and oxidizing effectively versus not. 

Jay Feldman:  Yep. Absolutely. And so that brings us to the impact of a low carb diet on oxalate clearance.

And there's a handful of things to a handful of things to consider here. For one, as we discussed, mitochondrial function in the kidneys themselves is directly related to the ability to clear out excess oxalate. And and we discussed the impact of oxidative stress in that situation as well.

And so with that in mind, the general shift, as you discussed, the general shift from glucose oxidation toward fatty acid oxidation involves an increase in reactive oxygen species production. We've discussed this many times before and so I'll link to some studies and articles going through the kind of biochemistry there and how that actually plays out.

But the important consideration here being that can drive mitochondrial dysfunction at the kidneys and therefore can contribute to some issues in terms of clearance there. So that's one consideration. But it there are a couple of other really important ones. Mike. I dunno if you want to touch on anything first before we dig into  those.

Mike Fave: This tape, this tails in what you're mentioning with metabolic issues and oxidative stress tapers indirectly to what I was just saying. So basically saying if you drive fatty acid oxidation, which you would have to drive on a low carbohydrate diet, then you'll lead to impairments in in, or you'll lead to increase oxidative stress in different tissues like the kidney, which could then create problems in terms of handling oxalate.

'cause as we talked about, the oxidative state of the kidney in previous episodes is important for the kidney to be able to protect itself against the lodging of crystals inside the kidney. What's an endothelial layer? So we basically don't want to, we wanna make sure that kidneys are functioning tip top shape and driving excess fatty acid oxidation would be, an or a negative effect of that or have a negative effect on that.

Jay Feldman: Yeah. Yeah, exactly. Yeah. And there are a couple of other factors here that I think are often overlooked when it comes to low carb diet that can cause issues here. One of them is citrate. So we talked a bit earlier about citrate, helping with calcium and calcium oxalate clearance as well having direct effects there in the kidney.

And while we can produce some citrate, in most cases, there's a pretty significant amount being consumed in the diet. Generally it's pointed to the stat that's often pointed to is about four grams a day. But when you look at the sources of that citrate, none of those are typically included on very low carb, keto or carnivore diets.

And this includes typically citrus fruits as some of the main sources, lemon, lime, oranges on from there. And some other fruits as well. A number of different fruits, pineapple cherries, berries all have considerable amounts of citrate. And then there's some in dairy as well. And typically these are foods that are omitted on low carb diets.

And so that lack of citrate intake could also be huge factor in terms of maybe contributing to symptoms with, similar amounts of oxalate exposure. But then. Not being able to clear those oxalates as well and potentially leading to more deposition and therefore more kidney be issues without enough citrate consumption.

Mike Fave: Yeah, and it, there's actually, there's a paper talking about using orange juice to help with kidney stones because the citrate content of the orange juice helps in, we've talked about this, helps actually minimize the formation of the kidney stones. It helps to prevent the crystallization of something like calcium oxalate.

So between like orange juice, having adequate calcium in the diet, those things alone could go a long way in helping to minimize the formation of oxalate here. So just, and these are relatively easy strategies to incorporate and again, like you didn't even have to do juice if you're concerned about juice.

Just having citrus fruit in and of itself would be a benefit on top of having the adequate calcium and magnesium intake. 

Jay Feldman: Yeah, exactly. And we'll talk through some specific strategies there later on, but obviously a simple one here as you're saying is just make sure you're getting enough citrate. And then the last thing to discuss here it's worth mentioning is the impact on general pH balance.

And so this was something that was touched on in that low carb diet. Basically talking about a shift toward a more acidic state. And we discussed this where one of the most important factors for maintaining proper [01:14:00] pH balance in the blood is carbon dioxide production at the tissues. And so when we're on a low carb diet, and our tissues have generally shifted from utilizing carbohydrates for fuel to utilizing fats as a fuel, there's a dramatic shift in carbon dioxide production where between the two different metabolic states, if you were running through them at the same rate, you would get 50% less carbon dioxide production.

From fatty acid metabolism. And that's not considering the difference in rate between oxidation of the two because you have a higher ROS to a TP ratio and a higher FA DH two NADH ratio from fat oxidation. That also slows the rate of respiration. So you're gonna typically have even lower amounts of carbon dioxide production.

And that carbon dioxide production helps to clear out the, basically to, to bring more bicarbonate into the into the blood and basically lead to a more basic state in the blood alongside bringing the calcium and sodium out from the tissues and into the blood. And so generally when you're shifting into a state of fatty acid oxidation, you're going to see more acidity in the blood, which then causes a couple of effects at the kidneys, as we talked about, where there's less retention of citrate and therefore.

Or excuse me, there's more retention in citrate and less clearance, which then leads to less clearance of calcium, less clearance of oxalate and calcium oxalate. 

Mike Fave: Not only does oxidizing fatty acids and producing less CO2 increase the acid load in the blood, if you have a high protein intake on top of that, with an increase ammonia production, re production from the amino acids like you would see on a carnivore diet, you also can add, you can also adjust the pH further.

That may lead to a circumstance. We have the, again, that higher acid load in the kidney, as we saw in the previous study, that then increases the risk of stone formation. So we have, again, like multiple pieces to the picture here, where a change in substrate or fuel utilization from carbs to fats, and then also having a higher protein intake, which you would typically see on something like a carnivore diet.

Where we typically see the dumping leads to circumstances where you can shift the pH of the blood. Into a context that allows for more stone formation. So this is, again, multiple pieces here by changing metabolism endogenously with the different dietary stuff where you can actually increase, number one, the production of oxalate.

And then number two, the increased association of oxalate with calcium to create m calcium oxalate crystals that can drive stone formation. And the, some of the symptoms that we see inside the carnivore diet with people with having oxalate dumping. 

Jay Feldman: Yeah, absolutely. And then one more point to mention here is that typically on these low carb diets, there's a significantly increased consumption of phosphorus, especially relative to calcium, potassium, and magnesium.

And all of those things also contribute to typically more acidity in the urine. And again, when the, as we mentioned earlier, when the urine is more acidic, that leads to less soluble calcium oxalate. So you can't clear out that calcium oxalate as effectively. So a number of  different factors here.

Kind of all pointing in that same direction. That can lead to some, some notable concern when it comes to oxalate issues on a low carb diet and the potential for a low carb diet to exacerbate them potentially despite a decreased calcium intake. Alright, with that, we'll wrap up there and in the next episode we'll be focusing more on a number of things.

But the main one will be what to do dietarily in order to prevent or reverse oxalate issues and how you can construct a bioenergetic diet that is more oxalate conscious if you need to. And also whether the standard kind of quote unquote bioenergetic diet is concerning from an oxalate standpoint.

So we'll dig into all of that in the next episode. But before that, Mike, can you share with the listeners where they can find more of your work? 

Mike Fave: Sure. They can find me here, obviously on the Energy Balance Podcast. Then they can find me on my YouTube channel, which is Mike fave YouTube. And then they can also find me on my website, mike fave.com.

Jay Feldman: Yeah, it's perfect. And as always, if you guys enjoyed today's episode, please leave a like or comment if  you're watching on YouTube. If you're listening elsewhere, please leave a review or five star rating. All of those things do a lot to help support the podcast and are very much appreciated. As always, to check out the show notes where I'll link to the studies articles on anything else that we referenced throughout today's episode, head over to jayfeldmanwellness.com/podcast.

And if you're looking to optimize, support your metabolism, lose weight, improve your digestion, get amazing sleep, rebalance your hormones, boost your energy, and so much more with clear action steps and strategies along with personalized guidance from me that head over to jay feldmanwellness.com/solution where you can find all of the information for the Energy Balance Solution program.

This program includes customized health coaching, a video library with a ton of videos on topics like regulating blood sugar, losing weight without destroying your metabolism, getting amazing restorative sleep, rebalancing your hormones and tons more. It also includes resources like a sample meal plan, supplement guide recipe book, and on from there as well as a private  community.

So head over to jayfeldmanwellness.com/solution to check out all the details and with that see you in the next episode.