Behind the Research: Revealing the Truth About Diet & DCM in Dogs

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Episode 20 • 11th October 2023 • The Pet Industry Podcast • BSM Partners

Dr. Megan Sprinkle: Welcome to the Pet Industry Podcast, connecting you with the people behind the passion, the leading experts in the pet industry. I'm your host, Dr. Megan Sprinkle.

Dr. Mary Cope: And I'm your other host, Dr. Mary Cope.

Dr. Megan Sprinkle: Hello, my pet enthusiasts. We know that you don't have to Google very far to understand that the answer to the best diet for dogs is riddled with debates and mixed opinions. You probably have also seen some controversial information on grain-free diets and heart disease in dogs. Researchers at BSM Partners have research hot off the press that will get into the heart of the matter, quite literally. This particular published research, as part of a larger study, might just change the way you think about your pet's diet. And, please check out the show notes for helpful resources. Now let's get some behind-the-scenes insights!

Welcome, everybody. I am very excited to have everybody here today to discuss your new study that was published in Frontiers in Animal Science, and it's focusing on the impact of different types of diets and diet ingredients on the heart health of dogs. So there has been a lot of discussion in the past few years; we're all very familiar with the idea around safety of grain-free diets that contain pulse ingredients, which we'll talk more about. And of course, everybody wants to know the results of this study so that we can make better decisions when it comes to selecting the right nutrition and the right diet for our pets.

So today we are joined by members of the BSM Research team, including Doctors Brad Quest, Stephanie Clark, Renee Streeter, and Sydney McCauley, as well as veterinary cardiologist, Dr. Stacey Leach. So it's really fun to get the behind-the-scenes from the researchers themselves and really dive into what you found in your study.

As we've talked a little bit about your research in previous episodes, which we can definitely link below in our show notes, the published study that we're going to be talking about today is actually part of a much larger study. So you are able to take a lot of information from all the work that you have done.

So just to start, let's recap a little bit on why BSM Partners, and you as a research team, conducted this study and then specifically, what is this paper going to be focused on around the heart and different diets. So Dr. Quest?

probably more so back in the: 2018

And so this piqued the FDA's interest. Us, being a consulting company in a research organization inside the pet food industry, it piqued our interest as well because what we wanted to understand better was the data and the information that the FDA had that they were basing these public releases on.

So we actually met with the FDA several times and, in those meetings, what we found out was that the FDA had no plans to actually do research of their own, they were relying completely upon outside or external sources to provide information that could help them or help guide them on what they felt like they should be doing.

In those conversations and with BSM Partners, as well as a lot of other research collaborators such as Dr. Leach, we came up with a study protocol that we felt like was very robust and we then decided to share that with the FDA because we wanted to collaborate with them. We wanted their feedback on our research protocol and they felt like it was a very comprehensive, very well-written protocol, but one thing they challenged us on was when we were looking at specific amino acids, primarily taurine and to a certain extent carnitine, in our research study where we fed different diets to different dogs and we took samples of blood and then would analyze the whole blood, and or the plasma, for these nutrients and amino acids, Dr. Burkholder, who is a very well-respected veterinary nutritionist, he's since retired from the CVM, but Dr. Burkholder challenged us on, how do we know that just because we can measure a nutrient in the blood that it actually correlates to what the levels are in the actual tissue? In this case, it would be the heart, or the heart muscle itself.

And we thought that was super interesting. And in theory, it's really a good idea. However, actually implementing those things can be very challenging, for a lot of reasons. And I know Dr. Leach will share a lot more of the details about that. We were actually able to make that happen, and the fact that we were trying to do all this during the height of COVID.

Dr. Mary Cope: So this paper addresses a number of different parameters, some of which are really quite complex, and I know I've designed a few studies before myself, and it can be really challenging to come up with, not only the treatments, but also the sample size, study duration, and what measurements and samples you'd like to collect. Dr. Streeter, can you help walk us through this process as it pertains to the study?

Dr. Renee Streeter: I sure can. Thankfully, we have such a great group here with all different areas of expertise, and we were lucky to even be able to share our protocol with the FDA and align on it with them too. But okay, so what we did, we had two breeds of dogs.

We used beagles and we used mixed-breed hounds. And we did that because there's also a consideration as to, again, breed, right? What happens in different breeds is one breed different than the other? So we have beagles and we have mixed breed dogs, and then we fed them four different diets. Each dog got one diet, but they were broken into four different groups.

And those groups had varying amounts of pulses and you'll hear this word "pulses" and what pulses are is a group of legumes essentially, in our study we used peas and lentils primarily, and those are the ones that are primarily considered when we're talking about pulses. So we had two diets that contained pulses and we had two that did not, and then the protein either came from animal protein primarily, or plant protein, or these pulses primarily. And within those four diets, we had all the same macronutrients. So macronutrients are protein, fat, and fiber, but the diets were all complete and balanced, meaning all of the nutrient requirements were met.

Dr. Brad Quest: Before we started feeding our four test diets, our four custom-formulated, the diets that we formulated, being the two-grain free and the two-grain inclusive diets, but before they started eating those, we wanted all the dogs eating the same diet. So they're all starting nutritionally at the same point, we fed Purina dog chow, which is the most common dry dog diet globally. All of those dogs ate dog chow for a minimum of three months and in most cases much longer prior to the study start.

You know what's really interesting in what Dr. Streeter talked about, when we actually formulated those custom diets, we were very specific to use pulses, or legumes that are very common in the pet food industry - ingredients derived from yellow peas and lentils. Those are going to be the most common, legumes that are typically used in the pet food industry, and, in addition, we used very high levels of those in those diets, levels that would be considered to be a lot more than what is typically seen in, commercial diets that are, being manufactured today.

What we really wanted to do was to test the extreme, like how much of these legume ingredients could we actually formulate into a diet to really try to put to the test, is there a way that any of these pulse-containing diets can contribute to cardiac dysfunction?

Dr. Mary Cope: Now, why didn't you just go pull diets that are, similar off the shelf instead of going through all this effort to make your very own?

Dr. Brad Quest: That's a really good question and the main reason for that is to try to control for variation. The goal of research is to test hypotheses but try to control for as many external variables as possible so, by us formulating these diets, we controlled for as much as everything, all the individual raw ingredients that made up these diets, we bought and got ourselves. We did nutritional testing on each individual raw ingredient before we even made the diets.

And the reason for that is we want to know exactly what the nutritional values are in the specific, pea flour that we use, or the specific chicken meal that we use because in pet food ingredients, as well as all food ingredients, there's natural variation, and that could be from the region of the country or the globe that it's grown in, to the season of the year, you know that it's grown and then harvested, there's always natural variation, and we wanted to be sure we knew exactly what the nutritional components were of both the individual raw ingredients as well as the finished test diets that they were made of.

Dr. Mary Cope: I think that testing had to be super important because, from my understanding, you didn't use any additional supplementation, to make these diets complete and balanced, right? It was all just from the nutrients present in the raw ingredients themselves?

Dr. Brad Quest: Yeah, that's correct. And the reason, for that is, there's theories and researchers out there that, I've talked about how different dietary components or legume components can bind or can facilitate nutrient loss. And what we wanted to do was to try to test, both these grain-inclusive and grain-free diets on their own merit without supplementing any additional, for instance, amino acids, we know that certain ingredients can be lower in certain amino acids, but through formulation because our Nutrition and Product Development groups are so good at doing these formulations, they were able to make these diets, no matter whether they were green inclusive or green free, complete and balanced, per AAFCO requirements, using only the individual raw ingredients without supplementing amino acids. And that's really important because we're testing the diet, we're not testing anything that was supplemented, to try to make that diet, be complete and balanced.

Dr. Megan Sprinkle: I just want to acknowledge that, personally, I know how hard that can be, so I just want to say kudos to the formulation behind this diet.

Dr. Stephanie Clark: It definitely was a team effort on formulating the diets. We had certified food scientists, we had PhD nutritionists, we had Board-Certified Veterinary Nutritionists, and board-certified companion animal nutritionists all formulating these four diets.

And that's because not only do we want to make sure that those nutrients are there meeting AAFCO, and the macronutrients are formulated to be similar, we also wanted to make sure that it would run and that it would feed well. You can make something and it goes through the extrusion process and not be extruded or you know doesn't appropriately absorb the fat that we're coating it with and so having a certified food scientist there to make sure that the amounts that we're putting in are appropriate and that are going to run appropriately through the machinery, and then we all were there while the diets were being ran in the facility. And this was really beneficial in the fact that we could help check the bulk density, we could adjust things as they were being extruded to try and get these four diets, not only nutrient similarities, but bulk density and Kcals and size and shape very similar.

Dr. Mary Cope: Obviously, you know, when we read the back of a bag, we're reading about ingredients, not nutrients. Can you walk me through why these nutrients themselves, like the little building blocks of these larger ingredients, are so important?

Dr. Sydney McCauley: Yeah, those infomercials at late night and it's always right around New Year's time where you see those diet commercials and it's always like, "You are what you eat - better New Year's resolution!"

So this, "You are what you eat" is a very true saying, but this goes into the dog food too, of understanding what they are eating and understanding how those ingredients influence those nutrients in their body. So what they're consuming and how those nutrients are absorbed in the intestinal tract and how that goes into their bloodstream and is utilized throughout their body.

Dr. Mary Cope: So, that's super interesting. I know I've read a paper about taurine being bound in some of these diets, and as many of us know, taurine is an amino acid that's important for heart health. Dr. McCauley, I know this is a particular area of interest for you. Did you do anything to account for taurine binding in the study?

Dr. Sydney McCauley: Taurine does play a major role in the conjugation or binding of bile acids, which we excrete from the liver into the gastrointestinal tract. So an increase in these bile acid productions could lead to an increase in taurine bound to these bile acids, right? And so then, because of that, there is the potential for loss of taurine through the GI tract.

And so this has been hypothesized in the literature about diets that contain high fiber and you all might be like, what does this have to do with anything? This goes back to Dr. Quest talking about our legume diets being high in legumes and legumes are known to have high amounts of what is called oligosaccharides, which are fermentable fibers.

And these fermentable fibers have been hypothesized, in the literature, to decrease taurine status in dogs which, in turn, may lead to what they're hypothesizing in the literature, dilated cardiomyopathy, because now the body does not have, or has depleted, stores of taurine. So what we did, if we go back to what Dr. Streeter was saying, we chose to keep all of our macronutrients the same, and we just really wanted to look at our ingredients. Also, we did a fecal study and we looked at bile acids and we looked at all the fecal characteristics that you would, and as we call it, the poop paper.

Dr. Megan Sprinkle: The fecal files.

Yes, we definitely got to dive in a little bit deeper into, I almost said deeper into poop, in our previous episode, and so we know that these diets were definitely digestible, and so now we can look a little bit closer on to the impact looking at the heart. And another interesting aspect of this study were the dogs involved with this study.

So you use two different kind of populations of dogs, all at the same time. You had some that were purebred Beagles, and then you had a mixed breed hound group of dogs and so I think this is really interesting because of some of the talk around individual dogs. And you're looking at these individual like ingredients as well.

So I think, since we have a cardiologist with us, Dr. Leach, what are your thoughts around specific breeds of dogs when it comes to, looking at heart conditions like dilated cardiomyopathy?

Dr. Stacey Leach: When we look at heart disease, one of the important things that I always stress to the students and my colleagues here is certain signalments - the age, the patient, the sex - those all play a role into what kind of heart diseases, certain individual patients may be predisposed to.

So we, really heavily look at those kind of factors to figure out what heart diseases we should be worried about, screening for, and looking for. So, for dilated cardiomyopathy, it's a disorder of the heart muscle itself. And that's actually the most common heart muscle disorder that we see in dogs in general.

But when you actually dive into it and what kind of dogs are predisposed to that, it's generally going to be our larger breed dogs. And we have certain breeds that are the, the highest offenders - Doberman, Pinchers, Great Danes - so these large and giant breed dogs, and it's often going to be, somewhat related to genetics, there are genetic factors, that have been associated with it, heritability, things like that. But then we also see some differences based on genders, between males and female dogs, and then there's always the question about how do other things impact, maybe not whether or not they get the disease, but maybe the severity of the disease, having a sedentary lifestyle versus a very active lifestyle. And there are actually ongoing studies currently across the U. S. that are looking at the impact of lifestyle in the progression and development of heart diseases like this. Definitely some very interesting things to look at.

Dr. Mary Cope: Most studies that I've read typically just use, beagles because they're a very common breed used in laboratory settings, but you also used the large breed mixed dogs as well. Can you explain to me, why you chose to make your lives even more difficult by using not one, but two breeds in your study?

Dr. Stephanie Clark: You, you definitely nailed it with why are we doing more to make our lives challenging? And you are correct in a lot of papers do use purpose-bred beagles, they are, they're common, they're, bred for this, they're tiny dogs, but it's important to look at other breeds and other size of dogs because we know that breed and size can also cause predisposition to heart diseases.

Our larger breed dogs are more likely to get DCM, but we also really wanted to look at mixed breed, and these were mixed breed hounds, these were also purpose-bred research dogs. We had no guarantee what kind of breed makeup we were going to get from these dogs, but we wanted to make sure that we were covering different breeds, different sizes, and try and make it a very, you know, good representation of the dog population out there.

And there had been previous notes that mixed-breed dogs were seen more frequently in the cardiology clinics than most cardiologists are used to. So that was really important that we wanted to include these mixed breeds. What is interesting is there was always this thought that mixed breed dogs are more hardy, that they should be more hardy.

They've got a lot of genetics going into play. And interestingly, there was a paper that was published about a year ago or within the year that talked about these mixed breed dogs still have the potential to carry their genetic predispositions. So for instance, if you've got a mixed breed dog and it has The genetic mutation PDK4, which makes them susceptible to DCM, it could be present in a mixed breed dog.

When we did some Embark testing on our mixed breed dogs, these were much more mixed breed than just hounds. These dogs were a pretty good representation of the dog breeds that are out there, they contained Collie and Husky, Golden Retriever, Hounds, Pitbulls. Interestingly though, too, about beagles is even though they are research models, and even though they are not genetically predisposed, to our knowledge, to DCM, they still can develop DCM. Going back to the FDA communication, there was a Beagle in there that was reported and earlier this year, I actually lost my Beagle to DCM. So we had a bunch of breeds hoping to represent a greater population, in the U.S. or, dog population.

Dr. Mary Cope: So it sounds to me like the general conception that Beagles being resistant to developing heart disease is maybe a misconception?

Dr. Brad Quest: So heart disease, that's a broad category. There are a lot of breeds that are predisposed to valve disease, predisposed to dilated cardiomyopathy and, various conditions. The dogs that we chose, the Beagles and the mixed breeds are generally accepted, in both veterinary medicine as well as the research community, as being less susceptible to cardiomyopathies, specifically dilated cardiomyopathies.

So it goes back to how we designed our study. We could have used dogs that are considered to be genetically predisposed, but, we chose, again, it goes back to trying to control for as many variables as possible, and if we would have used dogs that are considered to be genetically predisposed, that would be another factor that we couldn't control for in our research.

Dr. Mary Cope: Now, I noticed in reading over this that some dogs were excluded from the study. Is there a reason for that?

Dr. Brad Quest: Yeah, that's a real interesting, interesting fact. So we actually started out with more dogs than we ended up using. And the reason for that is we suspected this before we started that we might find, and we're going to call it subclinical abnormalities, but these would be abnormalities that a cardiologist could pick up in a dog's heart when viewing an echocardiogram that don't necessarily mean that the dog has a disease, and a good example of this is cardiac valvular disease. There's, four main different valves in the heart, and there might be a dog that might have, and most folks would probably have probably heard the term murmur or a heart murmur ,and all that is a leakage or a back-flow, whenever that valve closes, meaning there's blood that moves backwards because there's a little bit of a gap, in that, in those valve leaflets, or the part of the valve that actually closes. And most of the time, those are subclinical, meaning they don't really, they're not causing a problem and they may never cause a problem.

However, what we wanted to do is to try to ensure that all of the dogs that started in our study didn't have these types of abnormalities that could potentially introduce bias, or a factor in the study that we couldn't control for. And interestingly enough, we actually found several dogs, and again, these were all young dogs, that actually did have some of these subclinical or abnormalities that we detected on the echocardiograms that we decided, we don't necessarily want to use this dog because our cardiologists identified that. Again, trying to take out as many variables as possible, because, like we talked about earlier, and I know Dr. Leach talked about it, is that DCM is a multi-factorial disease, meaning there's a lot of things, that can contribute to it.

Dr. Stacey Leach: The other unique thing about this, and this has been a topic that's been of a lot of interest and a lot of curiosity amongst the veterinary community, was the length of our study.

This, as far as I'm aware of, and published to date, is the longest feeding trial that we've had - about a seven-month feeding trial, which is considerably longer than any other published, study so far. One of the other things that we also, that was unique to our study is we wanted to take a very global, picture, looking at the macroscopic level, and then also dive deeper, into the actual tissue, looking at the microscopic, evaluation of the heart tissue itself.

So we actually evaluated the heart using a variety of different diagnostic techniques. so looking at the heart overall. The most common non invasive method to look at heart size and function is an ultrasound of the heart, or an echocardiogram. And that actually just uses sound waves to generate pictures so we can see the heart tissues, see the heart chambers, how they move and see blood flow moving in and out of the heart.

And that's actually the standard criteria for diagnosing a heart disease, including heart diseases like DCM. But we didn't stop there. We also wanted to look at what is happening at the cellular level. And to do that, you actually have to get a piece of the actual heart tissue itself. And that is one of the unique things about this study is we actually did, grab pieces of tissue, the heart tissue itself to analyze that further.

Dr. Mary Cope: Dr. Leach, can you dive a little further into exactly what an echocardiogram is and why it was so important for the studies for our listeners who, maybe aren't used to hearing that word tossed around or aren't super familiar with the procedure?

Dr. Stacey Leach: Absolutely. So the echocardiograms, that's going to be our standard diagnostic test of choice to evaluate for any sort of heart disease.

And what it does is it basically generates a picture, so we can see each of the heart chambers, how big they are, how small they get. And the heart is a dynamic structure, so it's going to be contracting and relaxing. And so some of the parameters that we actually measure, we measure, how thick the heart walls are, we measure how big the left ventricle, in particular with DCM, how big that heart chamber is, and then how small it gets when it contracts. And we look at the differences in how big it gets when it relaxes and how small it gets when it contracts. You'll often hear us talk about certain echocardiographic parameters such as ejection fraction or fractional shortening. Those are basically just parameters that we can measure, that tell us how well the heart is moving in a real-time. how big does it get and then how small does it get when it's ejecting and pushing blood throughout the body? Actually, all of the research parameters that we reported in this project are the same parameters that we'd use in clinical practice, to make a diagnosis of any heart disease, but in particular for dilated cardiomyopathy.

Dr. Mary Cope: And then, so it sounds like the echo is a great way to look at the heart to see if, DCM is present or if there's any abnormalities in the heart muscle, but from looking at an echo, or even the biopsies themselves, can you determine, what the root cause of the DCM is from these measurements?

Dr. Stacey Leach: So that can be a very challenging task to, to take on. Dilated cardiomyopathy can be the end result of a variety of different types of heart diseases. Most commonly we think about it being a genetic predisposition where there is some sort of problem with the genetic coding that causes the heart muscle at the cellular level to be dysfunctional.

And that ultimately results in the heart getting progressively bigger over time and the contractility of the heart becoming progressively more fatigued over time, but we can see very similar things with things such as, inflammation of the heart muscle, myocarditis, if we have certain types of, really bad, and prolonged hormonal imbalances, if your thyroid hormone is not functioning appropriately and your thyroid levels are too low.

So DCM unfortunately is a catch-all. it just describes that we have a heart that is too big or dilated, and then it's a problem with the heart muscle not contracting. And so determining the actual cause where there's genetic or an infection, inflammation of the heart muscle, that's a little bit more challenging and does require more diagnostics.

Dr. Mary Cope: It sounds like there's a lot of different measurements happening. Is there any particular way that you went about to ensure everything was done in a consistent manner?

Dr. Brad Quest: Yeah, that's a really good question. Dr. Cope. So the advantage that we had in doing this research is we had the expertise and the experience of three different board-certified veterinary cardiologists that currently practice as well as teach in accredited colleges of veterinary medicine. And the beauty of that is, is drawing upon all of their experience. So one of the, one of the questions, and this isn't a new question, but it's been going on in the cardiology community for a long time is, how do you establish what's normal versus abnormal when a cardiologist is viewing an echocardiogram, which is Dr. Leach had stated earlier, is the most important diagnostic tool that cardiologists can use.

So we talked about earlier, we had Beagles, and then we had these larger, mixed breed, hounds, in our feeding studies, but the question remains is, how do you compare echo numbers and values and measurements, between dogs that have vastly different sizes?

What has been happening, and it's done this way in human medicine to an extent, is they normalize values. So there's a calculation factor that has been well accepted with the veterinary cardiologist to be able to take the values that they glean from the echocardiograms and use a normalization factor.

It's just a simple calculation so that we can then compare different sizes of dogs and try to establish what is normal and what would be considered abnormal. And, like I said, we leaned super heavy on the experience of our veterinary cardiologists. Now, it doesn't necessarily mean that this is the only way the cardiologist will evaluate echocardiograms to try to determine, is this dog's echo normal or is this dog's echo abnormal, but what it simply means is it's the most well, most currently accepted, methodology that's being used across veterinary cardiology as a whole and like I said, we feel very fortunate to be able to have the guidance and the experience of these academic veterinary cardiologists to guide us on this.

Dr. Megan Sprinkle: It's great to have so many board certified veterinary cardiologists participating in this study. They can bring different perspectives nationwide, but when you were designing the study, why did you decide to include so many specialists?

Dr. Brad Quest: I think that's definitely one reason, to draw on everybody's experience and expertise and to try to get everybody on the same page, so to speak, as far as the actual research, both the protocol, you know how we did the research and then the results.

I would also say another reason is to get everybody's clinical experience. When you look at this as a whole, meaning like the cases, that had been reported to the FDA, when you really start looking at a lot of the areas of the country that these cases were reported from, it's actually very few.

In other words, the cases that the FDA had isn't really a broad representation of all dogs throughout the country. There was a lot of dogs reported from the Northeast, a lot of dogs reported from the Mid-Atlantic and even Southern Atlantic states, and then a lot of dogs reported from the West Coast.

But really? Not a lot of dogs from the rest of the country. So what we found in talking to a lot of cardiologists across the country, both the colleges of veterinary medicine, as well as, private, referral, veterinary practice is that there, what they see as far as DCM diagnosis varies a lot. And so we felt like it was important to try to talk to as many cardiologists and then From that, try to engage as many to collaborate with us on this research.

Dr. Mary Cope: Yeah, I think that's super important. And it's always that's how BSM works, right? And you have a group of experts together and they all work together to make, whether it's research or new products, happen.

As we talk about research, I know one of the important things about research is we try to eliminate, as researchers ourselves, as many variables as possible that might confuse us or cause a biased end result. And sometimes we can be the variables, so we need to make sure that we're not contributing bias to the study, and that's done through a process called blinding.

I know that blinding was used in this study, so would one of you like to discuss how we use blinding to ensure there is no researcher bias?

Dr. Stephanie Clark: A double blinding is considered one of the highest standards in research to eliminate that bias. And so what we did is, the team made the diets and once they were made, they were put in coded bags.

So we had one person hold that code to unlock the key to a different code, that another person held. And this helps when we were analyzing the data, when we were collecting parameters, and even the individuals who were feeding the dogs had no idea what diet they were feeding. All they knew is that this, treatment one, treatment two, had no idea. So this is really important, especially when you go all the way through the statistical analysis being blinded.

Dr. Stacey Leach: Another part of the blinding process also involved, on the other end of the spectrum, obtaining the diagnostic images. So with the echocardiograms, those were all obtained by a sonographer who was blinded to the dogs and the treatments, obviously not blinded to the dog breeds, they have to see them there, but blinded to the diet treatments that they were receiving.

And then we had all of the images evaluated offline, so remotely, by three independent cardiologists looking to make sure that all the images were there, the image quality, was good, and that they were all diagnostic echocardiographic studies. And when they're looking at them remotely, they had no idea if it was a beagle or a hound dog, if they knew, they didn't know which diet, they were receiving, so they were just commenting on the images that we're seeing, we also were blinded to the time; we didn't know if the images were obtained on day zero of the study or if the images were obtained at day 210.

Dr. Megan Sprinkle: That sounds really complicated. I do not envy whoever had to go and get all these codes to write this paper. Sounds like a treasure hunt a little bit there.

Going back to some of the data that you were collecting, you talked about, looking at the echoes to interpret them and then you talked about getting back to the micro level. So you're also collecting heart tissue samples, which I mean, talk about getting real close to understanding what's going on with the heart muscle. How would you elaborate on really the importance of this very unique part of the study?

Dr. Stacey Leach: It's pretty easy to get blood samples and test the blood for nutrients and toxins and all sorts of things. But at the end of the day, you're making an assumption that what's happening in the blood is also what's happening in the organ of interest, or the tissue of interest, and that's not always the case. So there can be definitely some, things that don't correlate there. For this study, we thought it was also important to actually get right to the level of the heart itself and see what's happening at the cellular level. And to do that, we actually have to get a piece of the heart muscle, or what we call a myocardial biopsy. It's a minimally invasive procedure, so that we could look at them under the microscope and test those for various nutrients and look at the architecture, to see if it was normal or not, so it was a very quick procedure, very painless, and the dogs, woke up, recovered well from the procedure without any difficulty and were back, back up and eating their food right after.

Dr. Megan Sprinkle: I am still curious, though, is this something that's fairly routine when it comes to human medicine that you might get samples? Do you know?

Dr. Stacey Leach: Good question. It's definitely not routine in veterinary medicine. There are some clinical indications for doing it in veterinary medicine, but it does require a lot of specialized equipment. So a lot of expertise and you have to have a whole team there. So we had a full anesthesia team, and surgery team, as much as we could fit in a room, with the COVID, pandemic, but it does require a lot there. It is something that's more routine in human medicine, particularly looking for diagnosis of specific heart muscle disorders, looking at, heart transplant, rejections, things like that. So it's definitely more routine in human medicine.

Dr. Mary Cope: You brought up COVID. So I have to ask, given that this study started or, was happening at the start of COVID and COVID impacted pretty much every aspect of people's lives from their jobs to the accessibility of toilet paper. What were some of the hoops that you had to jump through to continue doing this during a global pandemic?

study started, around May of: 2020

So we decided that we would set up our own surgery facility inside, where all the dogs were housed and where we were performing this, which entailed having to procure all of the equipment that Dr. Leach talked about, which unfortunately did cause some delays. It set us back probably six to seven months to get all that going, but there's an old saying where there's a will, there's a way.

Dr. Stephanie Clark: And I remember Dr. Quest, we got asked the question that still haunts me to this day, "is it difficult or, and challenging, or is it impossible?" And now I feel confident saying it was just difficult, but when you're in the thick of it, especially during COVID, trying to put together an entire surgical suite, it feels relatively impossible, but we were able to pull it off, which is really neat.

Dr. Megan Sprinkle: Well, before we get to the results, I'm a nutritionist, so I can't let this go, but reading the study you had, I don't know if chunky monkey is the right term for some of your dogs, but in more scientific terms, they were a little overweight and you help them to not be. But this might be a point in the study where people, if they're reading all the details, might ask some questions about, body condition and how you approach that with these dogs. And, my guess is that was mainly the beagles, but feel free to, to say which dogs are the troublemakers here, but yeah, Dr. Clark, do you mind sharing a little bit more about that piece of the study?

Stephanie Clark: Yeah, it really important is feeding the dogs the appropriate nutrients, getting that nutrients in the body so we can actually assess those.

Some studies in the past have underfed dogs or overfed dogs, and so we followed the recommendation of the NRC to feed according to laboratory dogs. And when we got these dogs, unfortunately, some of them were a little chunkier and you guessed it right, it was the Beagles, but we wanted to make sure that we were feeding to ideal body weight. We wanted to make sure that we weren't helping these dogs stay chunky throughout the study. And while we were feeding them appropriately, we were feeding them according to NRC, we did feed to ideal body weight, which we did see some weight loss along the way. And actually, these dogs looked really great at the end of the study.

As a nutritionist, I love nothing more than seeing dogs that are ideal body weight. There's been studies that you know, show all the health benefits of dogs at ideal body weight. And so we did have some dogs lose weight, but all dogs stayed above a three out of nine on a body condition scale, which is, again, ideal, these were, four to five out of nine, which is really good, but we had to take that into account when we were normalizing these cardiac parameters.

And a lot of studies will look at actual body weight over time, whether or not the dog is getting bigger or smaller. And we actually took it to ideal body weight. And Dr. McCauley, if you, if I remember correctly, you found a really interesting paper that kind of talked about obesity and heart size and the relationship and how important it is to look at ideal body weight.

Dr. Sydney McCauley: Yeah, so there's not a lot. done in dogs looking at this. There is a plethora of work done in oncology and humans and obesity in humans and rats and, but seeing work done in the specific species you're looking for just makes your heart excited. The study did actually look at both actual and ideal body weight, and they looked at the parameters in each one and compared the two across similar to what we did, but they did a weight loss program.

Their results said that the differences that they found between actual and targeted and any significant differences would essentially be due to direct consequences of the weight change rather than like internal changes in the heart. And if it was a significant change across both, like actual and targeted, then it was an actual change in the heart, if that makes sense.

So then, for instance, they looked at cardiac function and when they normalized actual body weight, they saw significant changes, but when they normalized to ideal, they did not see those changes to be significant. That's where they had those conclusions of these changes were noted because we saw these huge fluctuations and weight, by normalizing to an ideal body weight from beginning into end, which is where we wanted them to reach, we could see the changes that were actually happening to the heart itself and not look at the weight changes with that.

Dr. Megan Sprinkle: There's a lot going on here in the study. We've got, we're looking at, impact of body weight and you're looking at four different diets, in case people have forgotten that by now, on all these things that are going on, two different types of dog populations, not to mention the individual dogs. And you're doing this over time. So there's a lot going on here. And so diving into, what you really found in this. study. I'm not going to lie. Sometimes it gets a little confusing and wording of, breed by day by treatment effect. Dr. Quest, do you mind kind of high level explaining a little bit about what was, what were your findings?

Dr. Brad Quest: Yeah, absolutely. And you're right, Dr. Sprinkle, it does get confusing even to the researchers and the folks analyzing the data. It's really important, and Dr. Leach was super instrumental, with his expertise and experience in helping us to determine, and I'm going to use the term what's normal and versus abnormal, and there's a fair amount of peer-reviewed research papers out there that actually tries to do that in the things that we were looking at. Like Dr. Leach had said, most folks focus on the echocardiograms as the primary tool to use when you're evaluating a dog's heart for a condition like DCM. So looking at cardiac chamber size, looking at the ability of the heart to actually pump or move blood is real important. and that's the type of information that the echocardiograms are going to give.

When we look at these, we'll call them reference papers, that have been used and are currently being used in the veterinary community to determine what's normal and what's abnormal, when you look at the dogs on all four of the different diets, whether it's the two grain free diets or the two grain inclusive diets.

When you look at those groups as a whole, all of those echocardiographic parameters, whether it was chamber size, or fractional shortening or ejection fraction like Dr. Leach said, are measures of the ability of the heart to actually pump blood, they were all considered normal. There was a few, individual differences, for example, when we looked at the dogs eating one of the grain-free diets, they did have lower fractional shortening, which is Dr. Leach says is a measure that we use to measure the ability of the heart to actually pump blood, but in one of the grain free diets was lower than dogs eating the two grain-inclusive diets.

Now, interestingly, this was actually only in beagles. In the hounds, we didn't see that difference, but I think it's really important to remember that even though the fractional shortening was lower in this one grain-free group, it was still considered normal. So sometimes in research, we can see differences but clinically it doesn't really matter, meaning those dogs are still normal.

Dr. Stacey Leach: Absolutely. When we looked at two different breeds is that we were not able to pinpoint a specific feature about any of these diets that would have led to any clinically relevant heart disease as detected via echocardiography, the myocardial biopsies, or even the cardiac biomarkers.

Although we've found some statistically significant changes here and there between certain breeds and days, none of it appeared to even venture on the realm of clinical significance.

Dr. Brad Quest: One of the other differences that we saw in our results was in the ejection fraction. So in our low animal protein, grain-free diet, the ejection fraction, and again, this is as the group as a whole, this isn't in individual dogs, but this is all the dogs that ate that diet as a whole, the ejection fraction was lower than the low animal grain inclusive, group or the dogs eating one of the grain-inclusive diets.

Now, this is also, interesting because it was no different than the other grain-inclusive diets. And then I will also go back and say the numbers were still considered normal. So again, a lot of times and researchers, we can identify differences. between dogs eating different diets or different treatments, as we call them.

But the end result is those numbers are still considered normal. And I think what's actually also important to note is all of the other parameters measured, whether it's the cardiac chamber size, Dr. Leach had talked about looking at the tissue samples to see what the actual, the muscle cells look like, cardiac biomarkers, which were the enzymes and proteins that we can actually measure in blood from dogs eating the different diets, those were all normal as well. And probably most importantly, and Dr. Leach touched on this earlier, was when all of the cardiologists viewed these echocardiograms blinded, meaning they didn't know what type of diet that this specific dog was eating when they're looking at their echocardiogram. But when they viewed all of these echocardiograms, none of them were identified as dogs that had any kind of cardiac dysfunction or abnormality. That's probably one of the most important takeaways of anything that we really saw in the study.

Dr. Stephanie Clark: And going back to your question, Dr. Sprinkle, about this breed by day, by treatment that you read in the paper, it really means that we can't isolate one individual parameter, that this multifactorial disease, DCM, we saw it as multifactorial, depending on the breed, depending on the day the samples were collected, and then depending on the treatment, we may or may not have seen a statistically significant change.

Dr. Mary Cope: And that's part of what makes these multifactorial diseases so complex, because there's so many different things that can play a role in their formation.

Dr. Stacey Leach: I do think that just means that we still have a lot more questions. So we have some answers, but we still have a lot more questions about what's really going on here. But it's not a simple, it's not a simple answer yet. I think if it was a simple answer, we would have found it by now.

Dr. Megan Sprinkle: Well I want to thank everybody for being here today and sharing, behind the scenes of your research. As we wrap up and we really want to talk about the main takeaways from this particular study.

From my understanding, you did not see any evidence of DCM throughout the study, regardless of the diet. So what are the big takeaways you would like for people to have at the end of this episode?

Dr. Sydney McCauley: Yeah, so that was a pretty broad yes, you did get that out of this whole thing. So you followed along this far, I'm glad that's what you got. but yes, so we did not observe any DCM or DCM-like changes in the dogs throughout the study. the study used an above-market inclusion rate of our pulse ingredients and the grain-free diet as well, so that was pretty, I think novel in that and that we didn't find any DCM-like changes because of that. There was no negative implications on heart tissue function, size, and blood work of the dogs eating the grain free diet. and dietary causation of the DCM was not isolated in this particular study either.

Dr. Mary Cope: As a veterinarian, in a clinical setting or in a small practice setting, how does this research, impact the way that you're going to advise clients that come in with questions about what to feed their dog?

Dr. Brad Quest: That, that's a really good question. I practiced for 10 years and then, but I've been in the pet food industry for almost 21 years. But I talked to a lot of my practice colleagues, and it can be very confusing. And part of that is, when you're a practicing veterinarian, you don't necessarily have time to do your own research.

You're going to rely on, independent researchers such as BSM Partners. You're going to rely on research done by universities. and in some cases, researchers done by specific companies or brands, so our goal is to try to make this as clear and concise and as simple as research can be, which that can be, super challenging.

But if I was a general practicing veterinarian and I'm reading the conclusion or the abstract of our research, my takeaway from this is that, based on this research and this dog's measuring all the things that these researchers looked at, I don't see any difference. In the cardiac parameters of the dogs eating the grain inclusive or the grain free diets from a clinical significance and that's important because when we say clinical significance, we're talking the actual health of the dog or the cardiac health of the dog.

And I think, Dr. Leach said it really well earlier, in that, when we looked at these dogs at the end of the study, both looking at the echocardiograms and all the blood work and everything we measured, but just looking at the dogs and their general overall health, these dogs are all completely normal.

And I think that's really what, pet parents, general practicing veterinarians are looking for. They're looking to answers to those questions.

Dr. Stephanie Clark: And with those key takeaways, I think this is important for our listeners who are pet parents, who are walking down the aisle and maybe a little confused on what to get or less than confident on what to pick up from the shelves that we didn't observe any negative changes to the heart and this high-pulse or, high-pulse inclusion diet and the grain inclusive diets, or if there's, lower animal protein or higher animal protein. So I'm hoping that this. gives pet parents more confidence in the diets that they're selecting for their pets that, over this time, we didn't see anything negative, and, you're not going to make a wrong selection on the diet for your dog based on this literature.

Dr. Brad Quest: When I get asked the question, and this usually happens when, we're representing one of our clients and their diets, and we're talking to their customers, which could be their key retailers or distributors.

And they ask us, do you have any reservations about feeding grain-free diets or even different diet formats to your own pets? And what I tell them collectively, and again, I'm going to use the word collectively, I think our BSM research team Probably has looked at this topic more than anybody in the industry, as well as the veterinary community.

And so I think we've probably assembled as much background and knowledge about this. and not just our own research, evaluating research that's been published by other folks. That's usually how I answer that question. So the simple fact is, do I have a problem feeding grain-free dog food to my own dogs? And that answer is no.

Dr. Stephanie Clark: Here at BSM Partners, we have dedicated quite a bit of our time and our resources into research for pets and to provide that confidence to pet parents, and we will continue to do, tackling DCM right now is just one topic, but there's always going to be another topic around the corner. There's always going to be a health concern and we are here to provide confidence to those pet parents when selecting a diet for their pet.

Dr. Megan Sprinkle: Thank you for joining us on the Pet Industry Podcast, a BSM Partners production with editing by Cliff Duvenois. Thank you to the podcast team, Dr. Megan Sprinkle, Dr. Mary Cope, Whitney Russell, Dr. Stephanie Clark, and Michael Johnson. If you want to learn more about our family here at BSM Partners, please visit our website at bsmpartners.net. And please make sure you are subscribed to the podcast, tell a friend, and find us here next time.

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