In this episode of the Pet Industry Podcast, your host, Dr. Megan Sprinkle, and the BSM Partners' research team explore the debate over grain-free dog food and potential links to dilated cardiomyopathy or DCM in dogs. They delve into the research done by BSM Partners and co-author, board-certified veterinary cardiologist, Dr. Stacey Leach regarding where in the body to measure two important heart nutrients: taurine and carnitine. Different places in the body where these nutrients can be measured include blood plasma, whole blood, and skeletal and heart muscle.

The researchers find that there is no correlation between concentrations of taurine or carnitine in blood compared to what's happening in the heart. Therefore, measuring blood levels of carnitine and taurine is not an adequate indication of heart health.

In this episode, you will also discover what is common in this heart condition in people as you hear from a human cardiologist.

The BSM Research team includes:

• Stephanie Clark, PhD, CVT, PAS, CFS, Dpl. ACAS, VTS (Nutrition)
• Sydney McCauley, PhD, PAS, Dpl. ACAS
• Brad Quest, DVM
• Renee Streeter, DVM, DACVIM (Nutrition)

Resources:

• Learn more about BSM Partners on our website.
• Learn more about the BSM Partners research.
• Episode on research on digestibility of grain-inclusive and grain-free diets.
• Episode to learn more about Dr. Leach's role in the research.
• Learn more about our guest cardiologist, Dr. Niteesh Chitturu.

Show Notes:

00:00 Introduction to the Pet Industry Podcast

00:12 The Controversy Surrounding Grain-Free Dog Food

00:35 The Importance of Scientific Studies in Pet Nutrition

01:00 Exploring the Link Between Diet and Heart Disease in Dogs

01:36 The Role of Blood and Plasma in Veterinary Diagnostics

01:49 Introducing the BSM Research Team and Their Study

01:53 The Limitations of Blood Tests in Diagnosing Heart Conditions

02:51 The Role of Diet in Human Cardiology

04:13 The Impact of Obesity on Heart Health

04:48 The Genetic Link to Dilated Cardiomyopathy

06:11 The Role of Nutrition in Heart Health

08:37 The Challenges of Measuring Nutrient Levels in the Body

09:05 The BSM Research Team's Approach to Studying Diet and Heart Disease

09:10 The Importance of Taurine and Carnitine in Canine Nutrition

11:17 The Challenges of Conducting Research in Veterinary Medicine

24:50 The Importance of Proper Sample Size in Research

27:34 Understanding Correlation in Research Studies

28:01 Understanding Correlation Plots

28:01 Pearson's Correlation Coefficient Explained

28:01 Correlation vs Causation: A Fun Example

28:37 Comparing Whole Blood and Plasma

28:47 Findings of the Study

29:19 Implications of the Findings

31:23 The One Health Approach

38:35 The Role of Pet Insurance

38:35 Key Takeaways from the Research

40:42 The Importance of Nutrition for Pets

Correlation Episode

[00:00:12] Dr. Megan Sprinkle: You have a lot of options when it comes to picking a pet food, and you've probably seen a bag of dog food that said grain free. If you ask 10 different people about their thoughts on grain-free dog food, you will get 10 different opinions, especially after there were news articles about a potential link to grain free diets and heart failure called dilated cardiomyopathy or DCM in dogs.

[00:00:58] So we will link those in the show notes.

[00:01:23] This research study gave very surprising results that could change how we look at the current tests we run to diagnose and monitor DCM. I mean, wouldn't it be nice if we just had a blood test to tell us everything? Well, looking at whole blood and plasma is the main way. Veterinarians try to see if certain nutrients that are important for heart health are at appropriate levels, but does that tell us what's happening to the actual heart?

[00:02:11] Dr. Megan Sprinkle: This means, when it says on blood work, This means what it says on blood work is not what is going on in the heart or the skeletal muscle. This is a huge finding as not only are blood tests being used clinically, but they are also being used in research to try to make determinations on heart status. So today we have the BSM research team, veterinarian Dr. Brad Quest, Board-Certified Veterinary Nutritionist, Dr. Renee Streeter, PhD and Board-Certified Animal Nutritionist, Dr. Stephanie Clark, and PhD nutritionist, Dr. Sydney McCauley. We also have co-author, Board Certified Veterinary Cardiologist, Dr. Stacey Leach, and we're bringing in a very special conversation with the human cardiologist, Dr. Niteesh Chitturu.

[00:03:07] He didn't mention nutritional causes at all. He said for people, they have two big categories based on if there's a problem with blood flow or not. Then he started listing,

[00:03:45] Dr. Megan Sprinkle: He talked about testing for HIV and even postpartum causes of DCM.

[00:04:02] Dr. Megan Sprinkle: That one was a new one for us. The closest we heard him mention diet and causes was diabetes. But that's because there are diet strategies to help with diabetes, not diet is a direct cause of the heart issue. Then we mentioned obesity. Obesity is a big problem in veterinary medicine, as about 60% of our pets are overweight or obese.

[00:04:44] Dr. Megan Sprinkle: So, if over 50% of dogs are overweight or obese, are we missing some potential risk factors for heart disease? Dr. Niteesh reiterated that actually similarly to veterinary cardiology, a lot of what human cardiologists see is a genetic link to dilated cardiomyopathy.

[00:05:33] Even if they don't have a family history, up to 20% of them can still have a genetic, abnormal, genetic screen. And a large percentage of patients who have idiopathic DCM can be found to have a genetic abnormality on the screening and it can be a big proportion of patients.

[00:06:06] We found this fascinating. So, human cardiologists are not thinking food ingredients when they are diagnosing DCM in people. But are there certain nutritional deficiencies that might go along with DCM in people like we think there might be in dogs? Well, our questions sparked interest; so, Dr. Niteesh had to dive a little bit deeper into the research himself.

[00:06:46] And, there are four big ones as far as, four that have been identified as far as thiamine deficiency. Deficiencies in selenium, which we get in our diet, can lead to dilated cardiopathy. Vitamin D deficiency and hypocalcemia, low calcium that results from that can lead to heart failure and cardiopathy.

[00:07:48] We treat that with high dose thiamine and see if they start to improve. From what I've looked into the same thing with deficiencies in those other nutrients. Even in the human world there definitely have been identified nutritional deficiencies that can lead to heart failure and cardiomyopathy.

[00:08:23] While we don't see very many alcoholic dogs, this does help us understand how important getting the right nutrients is to help the body function appropriately. I'm a veterinary nutritionist, I kind of think nutrition is important. But Dr. Niteesh then said the big challenge in nutrition.

[00:08:55] Dr. Megan Sprinkle: In veterinary medicine, and for DCM in dogs, you may have a doctor discuss looking at blood levels of taurine, and maybe even carnitine, depending on what they think is causing the heart disease.

[00:09:13] Dr. Megan Sprinkle: One of the things that people probably read when they were looking at or reading the different news press about, different types of food, specifically grain-free or with grains, and dogs developing a certain type of heart disease, dilated cardiomyopathy, they probably also read the term taurine, and so this is a really important nutrient that we may actually look at blood levels for, but I think it's great place to start with why is this particular nutrient and another nutrient that you've looked at that maybe didn't get as much press as taurine, but also carnitine.

[00:10:04] Dr. Renee Streeter: Not at all. Taurine is a non-essential amino acid for the dog, which means that the dog's body can make taurine from other amino acids.

[00:10:34] Carnitine carries fatty acids into the inner part of the cell, the mitochondria, to help make energy. Most of the carnitine stores in the body are in the heart or skeletal muscle. And then since about 60-70% of the energy produced in these muscles is for contraction of the heart, a deficiency in that carnitine, which shuttles the energy source can lead to heart dysfunction.

[00:11:14] Dr. Megan Sprinkle: Great. So, for dogs, taurine is an essential nutrient, but considered non-essential in the diet because they can make this amino acid from other amino acids that they can get in their diet. Both taurine and carnitine are important for the heart. So, how were these nutrients originally called into question when it comes to the development of DCM in dogs?

[00:11:54] In a lot of these research publications looking at clinical cases of dogs with DCM, pulling blood doing taurine levels and then kind of making these assumptions in the papers that whether the plasma, the whole blood taurine level came back is either within the normal range or low in some cases.

[00:12:30] That would equilibrate to levels that were actually in the heart muscle or potentially in the skeletal muscle. We had talked a lot about some of these research papers when we were meeting with the FDA. It was then very intuitive, a Board-Certified Veterinary Nutritionist, Dr. Bill Burkholder, who's actually now retired from the FDA, but when he was in his position there, he pointed out very astutely that doesn't necessarily correlate.

[00:13:27] And the reason this is important is because then, clinical practicing veterinarians could use taurine blood levels, whole blood or plasma blood levels kind of as more of a guide as another diagnostic tool. But we wanted to confirm or not necessarily always not that we knew we would confirm we had hypothesized that we thought it would, but we wanted to try to confirm that through this research.

[00:14:14] But when we're looking at deficiencies, are we looking at the blood, at the plasma, the skeletal muscle, the heart muscle, when we're talking about deficiency, where is that in the animal?

[00:14:40] You could have a deficiency in the blood and still have adequate taurine or carnitine in the heart to perform the various functions. It's really hard to know, but generally, when people are saying deficient it's because they've tested the blood. They haven't tested the muscle.

[00:15:18] there's whole blood, there's plasma, there are all sorts of ways, Dr. Leach, what are you seeing as most common when it comes to assessing these really important nutrients and just understanding where a dog's status may be?

[00:15:53] Whether that be from whole blood, which is, all of the blood cells and the fluid components, or we actually spin that down and separate it into its individual components of plasma, which is just a cell-free fluid, but that's often how we measure a lot of biomarkers in the body through the bloodstream.

[00:16:28] There's always been some level of debate on whether blood markers are actually viable surrogate markers for what's happening at the level of the tissues with carnitine, in particular, I think, there is some evidence that suggests that carnitine deficiencies causing DCM, can actually be due to a deficiency in the ability of carnitine to transport into the heart muscle cell.

[00:17:12] Dr. Megan Sprinkle: And that's why it's important that in research you have a sufficient number of animals, and you observe things over time.

[00:17:46] Dr. Stacey Leach: Oh, yes. There are not many people who actually do this on a clinical patient. There are minimally invasive techniques for doing this procedure, but it's not something that's going to be readily available to your general practitioner out in private practice.

[00:18:41] Dr. Megan Sprinkle: When we talked to Dr. Niteesh, he could relate to veterinary cardiology that echocardiograms are the bread and butter of cardiology, and when we asked him about biopsies, Dr. Leach was right.

[00:19:08] Dr. Megan Sprinkle: So maybe it's a good thing that biopsies don't have to be very common, but soon you'll see why this could also be perplexing when we're trying to understand potential nutrient deficiencies. Coming up next.

[00:19:37] Dr. Stacey Leach: Absolutely. We absolutely have to use analgesics and general anesthesia to be able to safely and painlessly collect these and of course, that's an added cost. General anesthesia isn’t cheap.

[00:19:57] Dr. Megan Sprinkle: And not all dogs are suitable candidates for this procedure either, due to age or health concerns, since we're potentially talking about dogs with heart disease.

[00:20:24] Dr. Stacey Leach: Yes, it was a pleasure working with the team here, and definitely shout out to all the dogs that participated in the study and all of the dogs did great throughout the study and found new homes.

[00:20:40] Dr. Megan Sprinkle: Dr. Quest, you did a great job in summarizing what got the team started and doing this research and looking into the different areas. I think it's great to go back a little bit into the study design of the paper because especially when we are looking at levels of nutrients, taurine and carnitine, I think it's good to remind people about the unique way that you designed and formulated these diets.

[00:21:36] Dr. Brad Quest: I think it goes back to a couple of different things, we had a lot of discussions with veterinary cardiologists, including Dr. Leach; and I should say Dr. Leach is, I would consider, the global expert on performing endomyocardial biopsies in dogs now.

[00:22:30] It's really a question that nobody could answer. I mean, there were a few studies that had been performed through the years on dogs that they had measured, levels of taurine and or carnitine. But they were really small sample sizes. The results were not really conclusive, and a lot of those were clinical cases where maybe everything and it controlled as far as what the dogs had been, what diets the dogs had been eating, had they received, and other concurrent medications in the study.

[00:23:30] Dr. Stacey Leach: That's a good leeway, the whole part of the study, to look at the nutrients and the ingredient list and ideally it would be nice if something as simple as a blood sample, would be able to help tell us exactly what's happening, at the level of the heart muscle, or even if, a skeletal muscle biopsy, which would be much easier to get them from the heart

[00:24:13] Really, to look at this, we needed to be able to get concentrations from all of those areas at the same time, so doing blood samples and looking at the whole blood and the plasma components, while also simultaneously obtaining samples from the skeletal muscle, which we obtained approximately one gram of skeletal muscle from one of the thigh legs muscles as well as small samples of heart tissue.

[00:24:46] Some of those samples that we collected were evaluated under a microscope or histologically to look for structural changes and we previously have reported on those findings; and found no differences between, the dogs based on the diet types that they're eating.

[00:25:15] Dr. Megan Sprinkle: Wouldn't it be great if there were a blood test for everything; that would make our lives so much better?

[00:25:39] And Dr. Quest, you also mentioned earlier, that you talked about sample size there briefly, and I am going to put on my nerd hat for a second if I haven't already. And because I think this is a really important part to talk about just research in general. And that is really knowing the proper sample size that you need for your research, because one, you want to make sure you have the right number of, in this case, dogs that you can actually interpret the data that you collect, so it's meaningful, but at the same time, you don't want to enroll more dogs than are necessary.

[00:26:21] Dr. Megan Sprinkle: This is to date the largest study that's been conducted in this area of vet med, but you did a lot of work to come to the number of dogs to be used in this study. And I know Dr. McCauley, you did a lot of groundwork in this to determine how many dogs that were going to be needed to be statistically significant.

[00:26:52] Dr. Stephanie Clark: Yeah, and part of that, what Dr. McCauley was saying about this power analysis, it determined about 64 dogs. We had 65 in our study, and that's, again, like you had mentioned, that's quite a bit of dogs, and we had to utilize research dogs to be able to control for And a lot of factors that were going on in the study.

[00:27:43] Not every dog is happy-go-lucky, just like humans, some of us are shy, and some of us are extroverts and outgoing. The same was our dogs. So, we relied on her, and I'm really excited about this upcoming episode, where we get to dive a little bit deeper into that because, since all of this, she's opened her own training facility, boarding facility where she can actually take animals that are fostered or needing to be adopted and do the exact same thing that she did in our study.

[00:28:35] Dr. Sydney McCauley: As you said, correlation does not equal causation. It's one of my favorite phrases that we always throw around. I like it because, just because something looks like it may be a cause doesn't always mean that it is.

[00:29:06] is it's comparing two values. So, for instance, in the study comparing plasma and whole blood on different, X and Y axis,

[00:29:25] Can we make those correlations or are they both stagnant? How does it look or does it look like mass chaos scatterplot everywhere? Is it a bunch of dots

[00:29:44] Dr. Megan Sprinkle: I always loved the little cartoon that was trying to describe correlation vs. causation. And the picture was, as more people were eating ice cream, the rates of sunburn went up. But if you look at the graph, it might look like eating ice cream gives you a sunburn, but in reality it's people eating more ice cream in the summer and that's usually when the sun is out, and so they're getting sunburn from the sun.

[00:30:18] And I liked your visual image too of the graph. We're going to look at whole blood and plasma and skeletal muscle and cardiac muscle.

[00:30:30] What were some of the things that you found most interesting?

[00:30:47] So that was what this was. And what we found with it was there was no strong correlation between plasma, whole blood, skeletal muscle, and cardiac muscle taurine or carnitine concentrations.

[00:31:26] Sadly, I don't believe that those are going to be reliable ways to know what's happening with the heart, especially when we're looking at evaluating for nutritional deficiencies causing or associated with heart disease This has also been looked at by some other researchers recently, some other colleagues here at the University of Missouri. They also recently found some discrepancies or lack of correlation between, taurine levels in the bloodstream and skeletal muscle, in a recent paper that was published in Frontiers as well.

[00:32:02] Dr. Stephanie Clark: Dr. Leach with this other paper being published, where do you, what do you think is going to happen next?

[00:32:15] Dr. Stacey Leach: Depends on who's funding the research projects. Sadly, in clinical practice, I was always trained to measure taurine levels when you're concerned about a nutritional deficiency. There's always been some question about whether carnitine in the bloodstream was actually a reliable marker of what's in the heart muscle and a few times I had actual clinical cases where I was concerned about that. I was unable to find any lab that would run carnitine levels, anymore. As far as moving forward in the future, I think we can rest assured that measuring blood levels is not going to be helpful in further looking at this disease process or in clinical patients.

[00:33:07] Dr. Stephanie Clark: Dr. Sprinkle and I had the opportunity to talk with a human cardiologist and we asked them if they look at taurine and carnitine in the blood. And they were like, no, not really. I was like, oh, okay. And they're like, you guys do that? We're like, yeah, it's also very expensive.

[00:33:55] Dr. Megan Sprinkle: I think we've known that fully understanding how to measure nutrients has always been a challenge. I think that's the thing about the specialty, being a nutritionist, sometimes it is just really hard to measure and understand. One, because the body is pretty cool. It likes to keep things in a very narrow range in the blood. And so, it's really hard to know.

[00:34:29] Dr. Megan Sprinkle: Dr. Quest, you've seen and participated in a lot of research in the pet food industry. How do these results relate to previous results? And in your experience, how has this information been used clinically? And will this kind of maybe throw a wrench into the research realm around DCM?

[00:35:15] I mean, animals that have had DCM. And then looking at some of the things that we looked at as opposed to controlled research. Where we had healthy animals and we were actually trying to see if, we could detect any differences in the dogs eating the different diets, in this case, what we're talking about in this podcast is, whether or not taurine and carnitine correlate to what we can measure in the blood to what we can measure in tissues.

[00:36:07] Dr. Megan Sprinkle: And Dr. Clark had mentioned that we had been able to speak to the human cardiologist, Dr. Niteesh, and it was really interesting to see the parallels of looking at heart disease. For example, an echocardiogram is their bread and butter for diagnosing dilated cardiomyopathy in a person. So, I'm like, oh, yeah, that's exactly right.

[00:36:49] So in my mind, it's like, how we learn from each other, both in human medicine, as well as in veterinary medicine.

[00:37:16] Dr. Stacey Leach: Yes, I think there's definitely been a big push, at least in the medical industry, for this One Health-driven, research and clinical medicine, because a lot of what we see in veterinary medicine mirrors, what they see in human medicine and vice versa.

[00:38:03] But there are some parallels between, heart disease in general. We both see genetic or heritable causes of DCM. Which has led to research in both fields. So, one of the research projects I'm most passionate about is looking at the genetics of DCM in Standard Schnauzers. And we found the gene mutation for that, disease process because just a year or two beforehand, gene mutation in that same gene was identified in people.

[00:38:51] Dr. Megan Sprinkle: I think you may have a Giant Schnauzer. Am I correct?

[00:39:04] Dr. Megan Sprinkle: And then Dr. Streeter and Dr. Clark, and Dr. Quest, we're all in a veterinary medicine field as well. So just your perspective as well when it comes to incorporating a One Health approach here.

[00:40:18] Dr. Renee Streeter: So, key takeaways, we can't unfortunately use blood measurements and skeletal muscle measurements to understand concentrations of taurine or carnitine in the heart muscle.

[00:41:01] So, as always, these things are exciting. They're going to help us understand the future, but every dog is an individual. If you are a pet parent who thinks your dog may have a heart condition or has DCM, you have to seek out a cardiologist and a nutritionist and work with them to find what's right for your pet.

[00:41:41] We're constantly learning and we're constantly growing, and we're adding to the knowledge that we have. It's important to read, up-to-date research, and like Dr. Leach had mentioned, there are more studies that are looking at correlation in the tissues and the whole blood and plasma.

[00:42:23] Dr. Megan Sprinkle: So, what's next? Well, we know that nutrition is still important for our pets. Even our human cardiologist said that diet can be a cornerstone to treatment for people with heart disease.

[00:43:09] Overall balanced diets such as that. Exercise is also really important in preventing cardiovascular disease. The American College of Cardiology, and the AHA as well, they recommend routine, regular aerobic exercise.

[00:43:31] Thank you for joining us on the Pet Industry Podcast, a BSM Partners production. If you want to learn more about BSM Partners, please visit us at bsmpartners.net. Make sure you are subscribed to the podcast and share it with a friend. We want to thank our podcast team, Dr. Sydney McCauley, Corrine Harris, Ada Thomas, Michael Johnson, Dr. Stephanie Clark, and Lee Ann Haggerty, and our amazing editor, Cliff DuVernois.