Neal: Hi, this is Neal from Growlies and I'm here with Daniel Orrego from KetoPet and Paws For Change. Now, you're also involved with-- Is it epigenetics? What's it called?

Daniel: Yes. Epigenix Foundation.

Neal: Epigenix Foundation. Thank you very much. Now, you have been involved in a lot of things to do with health around cancer and diet. That's why your work intrigues me so much. Tell me a little bit about you and how you even got into that, Daniel?

Daniel: Sure. My trajectory towards this space was really a little bit oblique. What I mean by that is, well, I did study the sciences in college. I ended up taking a hard date version from that and going into tech and spend a lot of time as a network engineer in the niche industry which was the travel technology industry.

I really only had occasion to come back into this, to the research field, by virtue of connecting with Ron Penna who is a CEO of Quest Nutrition. Him and I spent many many years together looking at the intersection of metabolism disease, specifically, how nutritional protocols impact both disease acquisition and disease management. That was the genesis of that. Of course that work has continued since that time.

Neal: Awesome. Then the Epigenix was the first thing you did and then you got into KetoPet, is that correct?

Daniel: Indeed. Well, it was almost concurrently. Really KetoPet was about trying to validate what we understood anecdotally in human trials. In other words, what we could know about case studies and small cohort trials regarding mainly brain cancer and breast cancer and how nutritional ketosis could impact those disease profiles.

What we also understood in rats studies where the use of exogenous ketones or calorie-restricted or carbohydrate-restricted diets impacted the mice in those studies and their ability to either delay disease acquisition or lengthen survival times.

The reason why we wanted to work with dogs was really twofold. One was because we love dogs [chuckle]. It wasn't difficult to go down that path. The other is because as far as a model goes, dogs are much better approximation of the human than a mouse is.

We could see disease appear in ways that were much much much closer to tumor models that you would observe in humans. Oftentimes, the tumor models that you observe in rats are induced or they're a result of genetic aberration and posed on the mice which doesn't really reflect how disease is acquired to humans.

That was really the start of it. Epigenix Foundation was really the non-profit that we wrapped around KetoPet because we realized was that the results we were getting from working with dogs, not only translated to humans but really translated across scientific modalities and across species.

We need a larger umbrella to capture everything that we were doing particularly because we took an interest in looking at novel disease markers as a way to assess cancer effectively at stage zero, which there's not a lot of people playing in that field. It was something that really piqued our interest because cancer is such a difficult, difficult disease to manage once you get past stage one.

Our thought I was, "Hey, look, if we can play the game of detecting cancer prior to the formation of a solid tumor, now, we've increased their opportunity to manage the disease effectively." That was really and truly what Epigenix Foundation was all about and continues to be about this day.

Neal: Awesome. Okay. You said an awful lot there. I just need to unpack a little bit for our people. [crosstalk] Some of the terms and some of the history they may not understand. I guess, let's talk about history. Real briefly, if we talk about humans and dogs and we go back to pre-agricultural era, lets' say between 7,000 and 10,000 years, which in the lifetime of our genome is not actually that long.

Because we can track the human genome back one-and-a-half million years before we were something resembling the modern human and then the dog we can track it back to the wolf about what? 40,000 years ago or so, something like that. During those times, it's theorized that we would probably have been in ketosis most of our lives. Do you agree with that?

Daniel: Yes. Well, I think that's something that observationally and deductively it's not a hard place to land at that conclusion, and here's why. Food insecurity, food scarcity or outright lack of food was a common occurrence in both the human and canine experience. I don't think it's controversial to accept that.

Neal: [crosstalk] The story that their animals have feed in famine?

Daniel: Precisely. Going through intervals of ketosis was a normal metabolic transition. In fact, when you look, it's so interesting because now-- In fact some of the best work on this is being done at the Applied Science & Performance Institute in Tampa, Florida.

Dr. Lowery and his colleague Dr. Jacob are doing a great work at looking at the performance effects of being in ketosis both cognitively and physically. There's actually some physical performance effects that go along with that.

For anyone who hasn't just eaten just for a while, let alone staved off consumption of energy for a period of time sufficient to induce ketosis, notices an up-regulation and energy notices an up-regulation and mental acuity. As an adaptive response to lack of energy, being in nutritional ketosis was something that actually aided its survival from both dogs and humans.

If your brain gets a little sharper when you don't eat, that might improve your chances of actually acquiring food. I think this is something that for anthropologists and evolutionary biologist, none of these topics are particularly controversial.

I think in fact what is controversial because it's only in the most recent epoch of human history, maybe the last 80, 90 years or so, that it's even possible for a portion of the population, mainly in Western countries, to never been in ketosis. That is controversial from an evolutionary standpoint.

In other words, that would constitute an evolutionary aberration in the modern epoch. In other words, the ability to Netflix and chill and eat the hot pocket and frozen pizza throughout the day is a modern phenomenon.

That was never a circumstance that humans could indulge in with any regularity even in the very, very recent past and of course in areas of the world where there's

tremendous poverty, food insecurity and food scarcity persists and hence the interval of going in and out of ketosis is still part of those population's experience. Yes.

Neal: You went with intermittent fasting, is what you're hinting at there. Do we see benefits from the short-term ketosis of intermittent fasting in animals, in studies?

Daniel: To a degree, and one has to be really careful about this. Probably the guy having the best conversation on this specific topic is Dr. Peter Thiel who has not only done a lot at looking at this, but has done an excellent job of collating and distilling the research and teasing out where we can have a high level of confidence in saying, yes, there is a benefit.

The studies that have yet to be done in this domain consists around comparative analysis of windows of time where one is not consuming. What is the benefit of eight hours and what is the criteria for managing that, and how do you compare that against 16, 18, 24, 36, et cetera, et cetera.

No one's put a fine, fine point on that yet, so it's hard to say what we know a lot about or what the metabolic responses are. To a degree, we know what the performance benefits are. For example, and this isn't new work, it's a little bit older work, maybe 10, 15 years old now. Dr. Jeff Volek has done 50 or 100 miles [crosstalk].

Neal: [croostalk] Daniel, sorry. We just lost you there for a second. As soon as you said the doctor's name--

Daniel: Sorry.

Neal: It's all good. It's the life. Welcome to the modern internet and cell phone, ultimately. It's funny. The thing that the phone does the worst is actually be a phone. [laughs] You were just saying, and I don't need to disrupt your train of thought, you mentioned the doctor's name and then we lost you completely. Could you just repeat …?

Daniel: Yes, I'll repeat. No problem. Dr. Jeff Volek, he's done the best work at looking at the performance effects of ketosis on ultramarathoners. These are the gals and guys that run 50 or 100 miles. What he found is that being in ketosis totally changed their training interval and so far that there was less injury, there was less inflammation, there was a greater ability to extend the training window in preparation for events.

What's also curious though is to look at what the nutritional protocols were during the event. These guys were certainly not in ketosis. Why? Because they had a tacit understanding that burning sugar during a performance interval is a huge performance benefit or performance enhancement. There's where things start to get really interesting, which is the conversation gets more nuanced because it's easy to say sugar is bad or carbohydrate is bad, but is it?

Neal: …

Daniel: Right. It's what are you doing with it and how are you doing it, right? Probably the best example or best mental model for this is you take two horses, one in the pasture, one in the wild. They're both eating the same grass. Grass has a tremendous amount of sugar in it. The horse in the pasture goes to founder. The horse in the wild doesn't. Why?

Well, one simple way of looking at that is that the horse in the wild is constantly facing predator threat which means they're constantly moving as they're eating. The horse in the pasture faces no predator threat. They just stand there all day eating. There's a huge difference in metabolic turnover even though both horses are extensively eating more or less the same things.

I think there's an energy consumption, nutrient partitioning, energy turnover, coefficient there that one has to look at when assessing the value of high glycemic carbohydrate as part of a nutritional program, particularly when performance is involved. These topics do tend to get somewhat layered, if you will.

Neal: Yes, and they're complex. You hinted at one of the real true benefits of a ketogenic approach to diet which is inflammation. It's considered an anti-inflammatory diet and most of our modern diseases are related to inflammation.

Daniel: Yes, and that's probably where we have the strongest body of data both in rat and human models looking at inflammatory markers like interleukin-6, high sensitivity C-reactive protein, homocysteine. You start looking at these body inflammatory markers and you start to realize that if you plot a curve from a high glycemic nutritional program and you start to transition to a lower carbohydrate calorie-controlled and perhaps even ketogenic diet, you see just the bottom drop out of those markers.

That is something that has been so consistently measured both formally and anecdotally. I look at those types of blood panels in myself all the time in both directions. I look at how can I make these markers go up, what are the things that can do that, and then how can I subsequently make them ....

You can pretty much tune your response to food inputs along those lines which is actually an interesting way of looking at nutrition because a lot of times the classic question is, well, what should I eat? What should I eat? Should I eat a Mediterranean diet? Should I eat a paleo diet? What should I eat?

What I like to do is invert the model. What I mean by that is first ask, what is the metabolic outcome that I wish to achieve? In other words, do I want to make my insulin go up, do I want to make insulin go down, do I want to induce inflammation, there may be very legitimate reasons to do that particularly to stimulate adaptive response, or do I want to keep my insulin steady?

Once you've determined that, then you select the distribution of macronutrients and total caloric density pursuant to that metabolic outcome. Finally, yes, you can select foods, but the window of foods that you would select dramatically decreases as a result of answering those first two questions.

Neal: Right, so have a goal?

Daniel: You're right. Yes. Have a goal. What's the outcome? What are you trying to get to? Then, finally, yes, pick foods that comport with that pursuit.

Neal: Right. A lot of people nowadays, we see an abundance or really a terrible tragedy of diabetes in our communities in both dogs and humans. They know keto as diabetic ketoacidosis. Can you explain the difference between a ketogenic diet and diabetic ketoacidosis which is your life at risk?

Daniel: Yes, indeed. The great news is it's very simple to understand what the differences are by just measuring glucose and ketones. With diabetic ketoacidosis, which is incredibly serious, if that's happening, bad things are ostensibly transpiring. One can understand that by seeing a high glucose number and a high ketone number. What would that look like? Will be glucose higher than 150 and ketones at 6 to 11 millimolar. That's ketoacidosis.

Ketosis is an entirely different metabolic profile.You would see blood sugars of 82 milligrams per deciliter and ketones 0.9, 1.2 millimolar. You see what I mean? Not only is it not the same thing. Measurably, you're looking at a totally different scale and relationship between serum glucose and ketone levels, between the two. That's, because they sound similar, ketosis and ketoacidosis, oftentimes are conflated as the same thing, but measurably, they couldn't be more disparate really and truly.

Neal: Then I know for a fact that somebody who goes to my store is going to watch this video and they're going to say, "I really, really wish I could do keto with my dog, but he's had pancreatitis in the past." Is it possible and how would you approach a ketogenic diet for a dog who's had pancreatitis and the owner believes that that dogs never supposed to eat fat again? That's [crosstalk], right? We see that in the store all the time.

Daniel: Right. First of all, pancreatitis in canines is incredibly serious. To take it seriously in your approach to addressing nutrition is the correct point of departure. The first step would be to take a measure. There's I believe it's a PLI test that you can take that will determine with specificity if the dog currently has pancreatitis, even low-grade. That's very, very important.

Once you have a measure, whatever that measure says, the first step that can be taken, which is a very simple one, is to begin to decrement carbohydrate from whatever the nutritional program is. Sometimes, that's easier said than done. What I mean by that is the easy part is to understand what it takes to lower carbohydrates. For example, if a dog is receiving a kibble of some sort of a Royal Canin or an Ol' Roy just feeding less accomplishes that. That's the easy part.

The hard part is people feeding their dog less. Oftentimes, pet parents are reticent to do that. That's the easy part. The requirement to get a dog into nutritional ketosis can be achieved, actually, without a ketogenic diet. What I mean by that is either controlling calories sufficiently on a daily basis or controlling calories through interval.

In other words, feeding on one day and not feeding on another can do two things. One is begin to ameliorate any acute pancreatitis symptoms, it can have that effect definitely, and it can slowly bring the dog's metabolism closer to a state of ketosis, even if they're not quite producing a high amount of ketones. Then what's also phenomenal about dogs is their metabolism is so fast.

Anyways, even dogs who have endured some nutritional abuse over time. Even without dramatically increasing fats and lowering protein and carb, dogs will oftentimes go into nutritional ketosis just by controlling calories and carbohydrates sufficiently. There's a spectrum for that. Every dog is different. What the great news is just even very subtle changes in nutrition can have profound effects that are very favorable for the doggie.

Neal: Let's talk about fat because fat is a key part of the calories in a true ketogenic diet. It's through fat that they get the majority of their calories in a ketogenic diet. What are the fats you would want to see in a dog's ketogenic diet? Let's talk about an average, medium-sized, let's say 50-pound animal. Are we talking like a quarter pound of butter a day? How much are we talking about? Coconut oil? Are we talking about olive oil? How much on an average 50-pound dog would I have to use?

Daniel: You bring out a phenomenal topic because one of the things that maybe it's not counter-intuitive, but maybe there's less emphasis or focus on it, is that for a dog or for that matter even a human, the requirement to add fat to induce nutritional ketosis is almost zero. What I mean by that is if you look at-- This is something that sometimes people forget. In fact, with dogs it's almost reflexive that you don't have to do that.

What I mean by that is if you look at the ketogenic ratios that are talked about in clinical practice, what I mean by that is I talked about for addressing refractory epilepsy and pediatric medicine. They talk about the 4:1, the 3:1, the 2:1, 1:1, et cetera. What is a 4:1 ketogenic ratio actually represent? What it's saying is for every 4 grams of fat delivered, correspondingly 1 gram of protein plus carbohydrate is delivered.

That boils down to about 90% of caloric density coming from fat. That's a 4:1 ratio. A 3:1 ratio is 87% of calories coming from fat. A 2:1 ratio is 82% of calories coming from fat. A 1:1 ratio is 69% of calories coming from fat. The reality is a 2:1, 3:1, 4:1 is ostensibly the same thing.

You get a pretty big fat calories break at 1:1, but even that you don't really need for either a dog or a human to go into ketosis. You can do a 0.5:1 ketogenic ratio, which is about 53% of calories coming from fat. Provided that you control overall calories sufficiently, both the dog and the human can go right into nutritional ketosis. That makes things incredibly easy when it comes to feeding your dog. Why?

Because if you go to the store and you buy a 9 to 10 ground beef, guess what? That's right around the 0.5:1 ketogenic ratio. The requirement more butter, add MCT oil or add ghee is simply not there. The only time that conversation becomes really relevant and important, and in fact should be focused, is if one is attempting to use a nutritional intervention like ketogenic diet to triage disease.

Then all of a sudden, then now you're having a very serious conversation about 4:1 and 3:1 for acute periods of time. As far as feeding a ketogenic diet everyday, just buying 80/20 beef that's right around between 1:1 and a 2:1 ketogenic depending on how much fat.

Neal: Most of the veggie-free mixes I have are generally right around there and that should be ketogenic diet essentially for a dog?

Daniel: That's exactly right. The great news is no one has to take any of this on faith when you can just simply feed those foods and measure glucose and ketones and you'll see. In dogs, what you really see is glucose tends to go down pretty dramatically. Dogs can run around in the low 60s and have all the energy in the world. Oftentimes, you don't see super high ketones and that's likely result of high utilization.

In other words, the dog maybe in ketosis but they're not expressing high ketones because what you're measuring in the pipe, so to speak, in other words in blood draws, ketones are low because they're being utilized in tissues. You don't see free ketones present in a blood measurement, but that doesn't mean they're in ketosis particularly when you observe the blood sugars can be so low and you have the dog has all the energy in the world.

Neal: Let's say I have a breed that's prone to cancer. There's many of them, your goldens, your breeds. There are a whole bunch of breeds now that are prone to cancer. Just to clarify for listeners, dogs get cancer more than every other mammal on the planet. They're great example of what we're doing wrong with diet.

If I have a dog who's 50 pounds and he's eating 450 gram food a day, and I'm just trying to be proactive in regards to giving him a diet that has some anti-inflammatory properties. I choose a ketogenic approach. What I'm hearing is, just basically using a low-carb, low sweetener, so no carrots, no root vegetable, primarily greens, things of that nature as their diet, and maybe supplementing with some oils or stuff like that, I'm doing what I need to do.

Daniel: Yes. What you're describing is an approximation probably the closest approximation you can get to what a dog might experience in the wild. They're carnivores, so they'll kill something but they'll also eat something that's already been killed. There's no cooked food unless you consider natural fermentation of the meat source in the sun to be cooked, so to speak.

They'll eat rotten carcass, they'll eat something fresh that they kill that the amounts of carbohydrate that they will consume in annual period, it will be less than 10% of the overall consumption food. It'll probably a carbohydrate source that's highly fibrous. If they're eating the viscera of say a rabbit, they might get some partially digested fibers. Nothing like a high glycemic rendered kibble. It's not even comparison at that point.

Maybe that's the way to think about these things, is to consider, "Hey, what's the closest approximation that I can get within a certain level of convenience and economic consideration to what a dog might experience in a while?" Right there that eliminates all bagged and canned foods. That goes out and you're left with any number of fresh food choices at that point.

Neal: I'm totally onboard with you. In that scenario, I got a dog, I'm trying to practice an anti-inflammatory diet. I'm doing all the things I think up is right. Where do you exogenous or dietary ketones come into play, or do they at all?

Daniel: These are elective choices. One of the things to keep in mind is that, in fact, maybe with very few exceptions, what's being sold as exogenous ketones doesn't quite meet that standard. These are picky considerations but they're interesting, so we can talk about them. What I mean by that beta-hydroxybutyrate is actually not a ketone, it's a carboxylic acid, and must be converted into body to a ketone.

Those conversions happen in different ways depending on which isomers you're using. There's some good science around determining which ones are most bio identical or most convertible into acetone and acetoacetate. The best work on this has been done by Dr. Angela Poff and Dom D'agostino, and Dr. Kessle and the whole crew there in Tampa.

What they've seen is that in a disease model, the introduction of exogenous ketones, even BHB ketones can have an impact both in vitro and in vivo on cancer cell lines. Now, is it chemotactic? No. What I mean by that is doesn't behave in a way that kills cancer? No it doesn't. What it can do is act as a competitive inhibitor to tumor metabolism.

If you look at those papers, you can see, yes, there's something there. As a lifestyle supplement, exogenous ketones may have a role to play when it comes to cognitive performance. It may have a role to play when it comes to controlling certain metabolic effects.

As a supplement that might make sense to give everyday, it's tough to have a high level of confidence that we know that that should be the case. The reason I say that is because with most of your BHB products, they're delivered bound to a mineral, magnesium, potassium, calcium, salt, et cetera. To get a clinically significant doses, the amount of salt that one would have to take in to get that payload of BHB is enormous.

The lab synthesized versions, the 1,3-Butanediol, the ketone diaster. Yes, one can acquire those. The ketone diaster is probably the best. One, because it's a combination of the native acetone and the CO acetate. A, they're extremely expensive, and B, they all taste like jet fuel. The practical side of truly delivering clinically effective dosages in compounds that are essentially lab synthesized and have actually been used in studies, the ability to do that is approaching zero.

Most of the supplements that are on the market, while they may have a performance benefit, and they may have a role to play as part of a lifestyle for getting peak performance or something like that is a normative inclusion in a nutritional program is tough to see where those fit. It doesn't mean that somebody won't figure that out. It's right now it's tough to have a high degree of confidence that, yes, this is something that a person should be taking every day, simply because the data hasn't quite been supportive of that so far.

Neal: Right. If I have a dog who's in an early stage, stage one cancer, they've been diagnosed, and I've fed kibble all my life and I'm looking to try something new and walk into a store like mine, of which there thankfully are more and more every year, because we don't just kibble.

They walk into a store like mine and they're trying to do this kind of thing. What simple advice would you offer? The first advice I offer is don't panic and do work with your cancer doctor, your oncologist, but the diet is their responsibility. The cancer treatment is the oncologists responsibility. What advice would you offer to those people?

Daniel: Frankly, I think you've nailed it. I think where a lot of people struggle I see this a lot is, and maybe you've experienced this yourself, "My dog has cancer. Oh my god, this is a setback. This is bad." "Now, how do you know that?" "Well, my vet told me." "Okay, well, how does the vet know that?" "I don't know." "Well, did they do a biopsy? "No. There's some indication in a blood panel that may indicate. I don't know." "Well, how did they know?" "That's what they said."

Oftentimes, the pet parent has received a diagnosis but doesn't truly understand from whence that came. Now, sometimes they have a little bit more information. Let's say, "Yep, they did a pathology and it says it's spindle cell carcinoma." "Okay, well, that's specific. Do you have the pathology report? Can we look at what the stage and grade of cancer is, what the mitotic index is, what the margins and cell differentiation?"

"No, I don't have that." "Okay. What was recommended?" "Well, I'm supposed to do chemo and radiation." Okay. Presumably, right? "What is the Delta on a Kaplan-Meier curve between survivorship with no treatment and survivorship with treatment?" "I don't know."

Neal: Yes, that's how … right?

Daniel: Right, yes. Oftentimes, what I find is that there's such a paucity of information. When I say information, I just mean facts about the disease itself, specific facts, and the correspondence between those facts and any given decision that a pet parent may want to make on behalf of their dog.

One of the things that oftentimes is greatly lacking is whole-body CT imaging of the dog, because it may be the case that a surgery has recommended, and so, "My dog's old, I don't want to give the-- I don't want the dog to have surgery." That could be in fact, the correct decision, particularly if there's been metastasis and the tumor load is large.

Iif you had whole-body imaging and it showed that this was an isolated tumor, at least at that time, and no metastasis, and that the prospect of a surgery achieving clean margins is high because you can tell that by imaging. Then all of a sudden now, the decision may be very different when it comes to making a choice about surgery.

For me, it's oftentimes before anything else happens, let's collect facts. Now there are challenges to this, not the least of which is economic. CT imaging is expensive. It could be a couple thousand dollars just to acquire an image. Doing more comprehensive histopathology is expensive. Doing blood panels that tell you more is expensive.

Oftentimes, there's an economic barrier to doing these things. Presuming that that's not there, presuming that the people are willing to incur those expenses, and oftentimes they are, they just don't know that those are options, it's really tough to make a recommendation.

Obviously, reflexively improving an animal's diet in any way shape or form is a step forward. It never hurts to make changes to nutrition which move the animal forward. That it will necessarily correspond to addressing disease is very difficult to know without having facts about the disease which tells you something.

For example, if you have a whole-body CT scan and you see that there's been tremendous metastatic progression from the spleen to all over the body, well, that's the stage three, stage four cancer. You have to prepare yourself to understand what that means, which is the likelihood of survival is very low. Now, if you have those facts at your disposal, that's may inform you about whether or not you may want to make dietary changes for the dog, particularly if that dog is effectively going into hospice at that time.

These are the route considerations, but I think you have it right that working with the oncologist working with the veterinary professional constitutes an important first step. Anything that you do to make improvements in other domains is completely within the control of the pet parent, for sure.

Neal: Certainly, I find when I talked to Dr. Ian Billinghurst, he wrote a book recently called Pointing The Bone At Cancer and he strictly points saying it's a dietary disease and not strictly, there's some cancers that he's very clear that they are created through genetic, bad breeding over generations and so on. That primarily cancer is a dietary disease, and that we have a medical system that doesn't care about diet and a diet system that doesn't care about medicine. That's why I say the diet is your responsibility, the cancer if for doctors.

Daniel: Yes. I think it also-- You're sort of developing a conversation, which I think is important at a meta-level, which is, look, the relationship between patient and medical professional is and must be, frankly, pursuant to success hopefully, collaborative. It must be collaborative.

There must be a back and forth, and there must be a consensus to work together, and most importantly, to troubleshoot. Medical professionals know this, particularly oncologists, whether it's a small animal veterinary oncologist or an oncologist that works with human patients. They know the limits of the medicine that they can deliver.

They're acutely aware of it. They face it every day. Hopefully, the relationship between patient and doctor can be one of exploration, of discovery, of troubleshooting, and of exploratory thought, all on behalf of the patient. Particularly, if it's a dog, the dog doesn't have much say. It's the humans who are advocating on that dog's behalf that have the say.

Neal: Now, we've been talking a lot about diet. We've been talking a lot about ketogenics. We've been talking about a lot about cancer. What are other some of the simple benefits you've seen from dogs going on to an anti-inflammatory diet?

Daniel: Well, the thing that always just impresses me, I should say, makes an impression on me is the change in body composition. This is something that it's visible. You could just see it. I see this all the time where I live in, in Los Angeles.

There's a dog park on every corner. I take my dogs to the dog park. You could just see the physical differences between my dogs and most dogs. Most dogs are obese. My dogs look like bodybuilders. They're ripped all the time. This is the feedback that humans love to do.

Transformation Tuesdays, say, "This is what I look like at the start of the year, but now I've made improvements to my physique. Look at me now. You can see that there's some improvement." I see now people starting to do those with their dog. "Here's my dog. He is a little bit of a Chunky Monkey dog, but now look, I've made some alterations to his nutrition. Look how lean and trim the dog is."

Dogs in the wild, if you look at them, they look like Olympic athletes. They're lean, they're muscular. You can see the separation in the muscles. You can see the striations in the muscles when they run. You could also see that if you take a dog skin and you pinch it, and it's squishy, that's not necessarily fat, oftentimes that's water.

That water is there because of a preponderance of carbohydrate. Just the physical changes in the dogs, the brightness in the eye, the energy levels. I think those are the things that people respond to most favorably. The thing is these dogs metabolisms are so phenomenal, you don't have to wait three months. You just have to wait three weeks and you see it. I think that has the most profound impact.

The other thing that people, and I get calls about this like, "Hey, did I mess up my dog?" "What do you mean did I mess up?" "Well, they're not pooping as much. Did I hurt them?" "No." The volume of stool by definition decreases once you pull out those high glycemic carbohydrates. A lot of times, the reason also dogs have a high volume of stool is because there's cellulose in a lot of dog foods put in as …

Neal: …

Daniel: Yes, exactly. Those changes are to be expected even though for sometimes people they're shock by it. It went from this huge thing to just these little pellets, but that's about right.

Neal: I mean they're facultative carnivores. Then when we feed them a carbohydrate diet, and they have very little amylase and almost no, or that their pancreas makes. They can't really actually digest anything. They're getting the nutrition from what is sprayed on from the vitamin pack that was imported from Asia.

Daniel: Yes. That's a challenge. In fact, you're speaking to something that's worth considering particularly when it comes to micronutrient because that's a big part of the landscape of discussion. The actual payload of micronutrient in any given commercial kibble varies wildly because it really depends on when in the manufacturing process it's introduced.

The reason why that's important is because you may introduce the requisite amount of micronutrients, and there's another debate whether it's synthetic or not. Presuming that the right amounts of each thing are there, if there's a subsequent heat process, the net results is that they're not there, and so that's a challenge.

Sometimes there's challenges just in the other direction which is there's too much of something. Often times, that comes as a result of a co-packer not having a mixing protocol down correct and things like that. Micronutrient is definitely a challenge when it comes to commercial foods. The greatness is if you look at dogs in the wild, this is an important thing to consider.

Zero dog eats a balanced nutritional program, zero. They go through periods of deficit, they go through periods of abundance, and there's definitely an interval of having sufficient micronutrient balance. The great news is that they're built to endure that. Now that said, that's not an endorsement that domestic dogs should somehow have to endure that.

The point being that if a dog is eating a fresh food diet, even if the micronutrient balance isn't perfect. That's not going to move them backwards dramatically unless that deficiency is sustained over a long period of time. Then, yes, you can run into trouble. The great news is, these are easily correctable things just with micronutrient supplementation.

Neal: Yes, and variety, and just changing things up on a regular basis.

Daniel: Precisely. Yes.

Neal: That's awesome. Now I just want to touch on some of your work with some of the nonprofits you've been working with because I got to say, you're pretty awesome dude. You're doing some great work.

Daniel: My self-esteem is rising [laughs].

Neal: Mutual admiration. It's all good. You've done some really good stuff, Daniel. KetoPet Sanctuary. I don't think you're with that organization anymore, but you were with them as one of the founders. It's an exceptional organization offering great info. Are they involved in the studies around cancer in dogs and diets or are they just … people?

Daniel: Yes. The focus for KetoPet now mainly revolves around education for pet parents, and they continue down that road. Much of that is really collating and bringing to the fore the great work that other people are doing. My focus has been primarily now on Paws For Change Foundation.

Neal: I'm headed there.

Daniel: Yes, which really takes the-- KetoPet was mainly focused on cancer, but Paws For Change is really about some of these broader issues like … that's very important. Dr. Karen Becker I think has done a phenomenal job of at least bringing consciousness to this idea that, "Look, the data, the science is now showing us that removing hormone production actually does not incur a benefit overtime because it stresses the adrenals. It has all kinds of effects that actually down regulated animals capacity to perform adequate immune function."

She's been just a fantastic advocate for surgical techniques that essentially allow a spayed or neutered animal to remain intact just preventing the ability for that animal to procreate. That's really, really important. That's a big issue that we care a lot about.

The other thing that we've done over the last year is a project called Know Your Pet Food. You can see the results of that at knowyourpetfood.org. Where we actually take commercial food products, pet food products and subject them to very, very rigorous third partly lab testing. What comes out of that is just absolutely fascinating.

For example, we looked at a popular vegan dog food, and we did genetic testing on it, and found that I think that there's horse and rabbit or something in it. Now obviously in inconsequential quantities, but what is that reveal? It reveals that in all likelihood that kibble was produced on a line that also produced meat based products.

Whether or not you think feeding vegan pet food is a good idea, and there's a conversation to be had there for sure. Anyone who's buying that product would likely take a second look at it if they were to understand like, "Wait, this actually has trace amounts of meat in it. That wasn't why I was buying this."

There are interesting discoveries like that. To get back to your point on micronutrient, that's where we really started to see the net payload of micronutrient was just all over the place. In many instances, micronutrients were completely absent, or in such proliferation that one might be concerned about giving the dog too much.

These are only the type of things that one can discover by doing this very, very precise third party lab test, and looking at this because these aren't the things that-- The dog food companies do these tests themselves. They just don't publish the result, so these were just sharing the results publicly.

Neal: They continue proprietary. So that knowyourpetfood.org?

Daniel: Yes.

Neal: … pawsforchange.global, is that correct?

Daniel: Yes, that's accurate.

Neal: Awesome. I'm just trying to get it right. Then are you still involved in epigenetics?

Daniel: Tangentially, yes. Ron and I still maintain a correspondence around that. He's continued. Him and his team scientist have continued to pursue any number of initiative surrounding early cancer detection. One of the big victories that has developed in the last couple of years is the small cohort study we did a couple of years back with brain cancer patients at Cedars-Sinai has now developed into a study Cedars run by Dr. Hu and Dr. Black.

That they're controlling and looking at using ketogenic diet as adjuvant therapy for your traditional temodar and dexamethasone treatments for brain cancer patients. Epigenetics continues to exert its influence in that domain from both people and dogs.

Neal: That's awesome. I guess what's the final piece of advice? We'll wrap this up. I know you have another appointment coming up here. What's the final piece of advice, or the final word you would like to say to anybody who's interested in this? Where would you point them? How would you help them understand what to do next?

Daniel: This may sound a little nebulous, but being curious is probably the attribute that leads to the most interesting discoveries and also encourages people to take ownership of the outcome. One of the things that's so interesting and also so challenging about working with dogs is while they're phenomenal communicators, sometimes we as humans aren't the best recipients of that communication.

Truly understanding what a dog's experiencing, what they're going through, and how they respond to whatever it is you do on their behalf is not the easiest thing. What I find is that for me, really staying in thatplace where I'm curious, it constantly in a place of discovery, puts me in a position where I'm constantly learning which is very satisfying, but oftentimes it puts me in a position to do better work on behalf of my canine companion.

Obviously, for people who are local to your area, being able to go in your store and literally just hang out and talk will probably do more for their dog than any other thing that they do because the conversation that transpires in your ecosystem is going to be one that opens people up to considerations that just aren't part of the popular consciousness. They're becoming mainstream but they're not quite mainstream.

It's not mainstream that it's reflexively self-evident that a fresh food diet is appropriate for canines and felines. That hasn't happened, yet we're closed. We're closed. The more people can hang out in places like yours, I think the more broad-based that conversation will become.

Neal: Then the other thing I would add is people check out the dog cancer series by Rodney Habib. It's … or well highlighted in that series. We loved it. To be honest, there's so much there. It's so voluminous. I haven't seen it all, know that I ever can see it all, but if you want to dive in deep on dog cancer, that's an exceptional resource.

Daniel: Indeed, it is a weighty tome of information. I think it's a six-DVD set. One of the things and hopefully we'll get to it this year is to do a feature edit of that that's 80 or 90 minutes so people can get the gist of it. That definitely constitutes an exceptional resource because it correlates all the top lines both in human medicine and small animal veterinary medicine and focuses the conversation on the intersection of metabolism and disease as pertains to cancer.

Neal: Beautiful man. Thank you very much. I think we'll wrap it up there. Daniel, I can't say thank you enough. This has been very kind of you to give us your time today.

Daniel: No, I appreciate being able to connect, and let's do this again soon.

Neal: I'm just going to stop recording there.