Literature Discussed: "Responses in randomised groups of healthy, adult Labrador retrievers
fed grain-free diets with high legume inclusion for 30 days display
commonalities with dogs with suspected dilated cardiomyopathy." Bakke, A.M., Wood, J., Salt, C. et al. BMC Vet Res 18, 157 (2022). https://doi.org/10.1186/s12917-022-03264-x
Key Takeaway: Dogs eating a grain-free, legume-rich diet developed changes to their blood parameters after 30 days which are similar to changes seen in dogs diagnosed with DCM, which provides early evidence of potential pathology.
Summary: In light of ongoing concerns of diet-associated/non-hereditary DCM noted in the US among dogs eating grain-free and legume-rich diets, researchers conducted a short-term (30 days) feeding trial on a small group of Labrador retrievers. These dogs were selected from a colony at the Waltham Petcare Science Institute. Prior to inclusion, all dogs had baseline blood parameters measured as well as cardiac clearance via echocardiogram with a boarded cardiologist. 5 dogs were fed a grain-inclusive, no-pulse legume diet, and 6 dogs were fed a grain-free, pulse legume-rich (60% inclusion) diet. These were experimental diets formulated for the purposes of the study. Blood work was checked on days 0, 3, 14, and 28. Additionally, urine taurine was measured. The dogs were scheduled to receive end-of-trial echocardiograms, but due to the cardiologist falling ill, only six dogs were scanned.
Literature discussed: "Effect of diet change in healthy dogs with subclinical cardiac biomarker or echocardiographic abnormalities” Haimovitz D, Vereb M, Freeman L, Goldberg R, Lessard D, Rush J, Adin D. J Vet Intern Med. 2022 Apr 14. doi: 10.1111/jvim.16416 Key Takeaway: Heart abnormalities in otherwise healthy dogs eating grain-free diets can be resolved/reversed with a change of diet. This is consistent with the findings of multiple previous studies as well as clinical observations.
Summary: A recent study (Adin et al.,2021) revealed elevated levels of biomarker cardiac troponin I in healthy dogs eating grain-free diets as compared to dogs eating grain-inclusive diets. This biomarker has been associated with damage to cardiomyocytes, the heart muscle cells. It was proposed that elevations of that marker in dogs eating certain diets may be attributable to low-level cardiac damage. In follow-up of that finding, researchers continued to monitor a subset of cases and measure serial levels of that marker after a diet change. That data has now also been published in a new paper (Haimovitz et al., 2022).
It's been four long years since the 2018 announcement from the FDA about a heart disease called DCM and it's potential link to certain types of grain-free or pulse-legume heavy diets, and the conversation is still dominated by disinformation.
Three and a half updates from the FDA and eight epidemiological studies later, there's a lot we still don't know. There's a decent bit we do know, too. We know enough to make risk-minimizing decisions based on the information available, while research continues into the foreseeable future, and these risk-mitigation decisions have the potential to save lives. We know that dogs are still being diagnosed and passing away from this disease. Unfortunately, the narrative available to pet owners through social media and trending articles isn't one that reflects the research and the reality in veterinary clinics.
Dilated cardiomyopathy is discussed on this site so often, people are often surprised when told I don’t intend to specialize in nutrition or cardiology. My interest in this topic is fueled instead by a passion for countering misinformation and providing education to the pet owning public, as well as enthusiasm for epidemiology and emerging disease science. On that note:
“Prospective study of dilated cardiomyopathy in dogs eating nontraditional or traditional diets and in dogs with subclinical cardiac abnormalities” was published 03/17/22 in the Journal of Veterinary Internal Medicine, with authors representing both nutrition and cardiology. The paper is open access, meaning anyone can read it without a login, subscription, or fee. In as few words as possible, the main findings of the paper are summarized at the end of the abstract, “Dogs with DCM or SCA [subclinical cardiac abnormalities] previously eating NTDs [non-traditional diets] had small, yet significant improvements in echocardiographic parameters after diet changes.”
A new research paper from BSM Partners was published this month and has already started to circulate online, ostensibly addressing the question of whether DCM cases have increased over time as grain-free diets have become more popular and widely fed. As a reminder, BSM Partners is a consulting firm that formulates pet foods for various companies, including Zignature, one of the top named brands associated with the FDA’s investigation. Employees of this company were the authors behind a widely criticized, non-systematic literature review on DCM published in 2020. Their conflict of interest on this subject has also previously been discussed in an article by Dr. Brennen McKenzie, known on his blog and social media as SkeptVet, and still applies to the current paper. Undisclosed for this paper, BSM Partners also received explicit research funding from several pulse legume interest groups.
To preface, a well-conducted study such as this could provide useful information to add to the developing issue. Unfortunately, this particular study failed to collect sufficient data, and in being published despite that, paints an incomplete picture that cannot provide many meaningful conclusions. While the findings can be easily characterized to dismiss the notion that atypical DCM cases, as being investigated by the FDA, are linked to certain grain-free or legume-rich diets, the striking limitations must be given consideration.
September 21, 2021, the FDA CVM hosted a virtual Listening Session on the Oversight of Pet Food. In addition to the live, recorded session of oral presentations, a comment docket was opened for public submissions and closed 11:59PM EST on 10/25/2021.
In total, the docket has 137 published entries. Broken down by topic:
~20 pertain to the use of 4D (dead, dying, diseased, down) meat in pet foods
~12 are on the subject of transparency and access by the public to FDA (and/or AAFCO) meetings
~12 are in regards to various other issues or general opinions of the FDA
Nearly 100 are about diet-associated (non-hereditary) dilated cardiomyopathy (DCM)
Of those, a handful are from concerned pet owners, advocates, and veterinary professionals. The vast majority, however, are the heart-wrenching personal stories of affected pet owners and their dogs, including those deceased, those continuing to battle, and those recovered. These pet owners represent only a minuscule fraction of the over 1100 complaints submitted to the FDA (as of 7/20/2020) and yet they are a poignant reminder that this issue is more than data, statistics, research papers, and debates between academia and industry.
There are real dogs, real people, real families, and such real heartbreak underlying this investigation. Many of them have called on the FDA to take more action towards this issue.
Research Cited: August 5, 2021 "Investigation of diets associated with dilated cardiomyopathy in dogs using foodomics analysis" Smith et al., Scientific Reports volume 11, Article number: 15881 (2021) https://doi.org/10.1038/s41598-021-94464-2
If you aren't familiar with the ongoing investigation into atypical Dilated Cardiomyopathy in dogs as it relates to diet, please see the Comprehensive Diet-Associated DCM Q+A and Nutrition page for additional information and resources.
Much of research investigating diet-associated DCM in dogs thus far has focused on the clinical pictures of affected and unaffected dogs in relation to their diet and patient factors. New research published in the open-access journal Scientific Reports took a deeper look, instead, at the diets themselves. This research took an approach previously dubbed 'foodomics,' or the in-depth study of food, nutrients, and their relation to individuals, health, and disease. While the findings of this study did not identify a definitive cause or mechanism for the atypical cases of DCM that have been seen in recent years (and continue to be diagnosed), it did open several doors for further research, bringing us one step closer to identifying the problem. Because Scientific Reports is an open-access journal, anyone can read the paper without paying. However, the methods and analysis are very technical, and may be less approachable for some readers. For that reason, important information is summarized below in a way more readily accessible to the average pet owner.
Background: Research in the 1980s-2000s previously linked DCM in both cats and dogs to taurine-deficiency, and in dogs to L-carnitine deficiency and certain lamb and rice diet formulations. Currently, there is concern regarding a link between grain-free and/or high-pulse diets and DCM in dogs. A timeline of this current concern is as follows:
Another retrospective study (Walker et al. 2021) concerning dilated cardiomyopathy in dogs was made available for pre-proof access, meaning that the article has been peer-reviewed and accepted for publication, but will undergo some further editing/formatting for final display in the journal. This research, published in the Journal of Veterinary Cardiology, can be accessed with a subscription or single purchase, but is otherwise not available to the general public.
The study itself is somewhat similar to the paper published in December (Freid et al. 2020). It is a retrospective analysis of dogs diagnosed with DCM and CHF (congestive heart failure) at NC State University College of Veterinary Medicine between 1/1/2015 and 07/10/2019. Dogs were excluded if their diet history was unknown. The analysis divided dogs into two groups based on whether their diet was grain-free (GF) or grain-inclusive (GI) at the time of diagnosis. Dogs eating GF at the time of diagnosis were switched to GI as part of the treatment. They're therefore referred to as pGF (prior grain-free). The authors further divided the pGF group based on the length of time a GF diet had been consumed (6 months - 2 years, 2-3 years, and 3+ years).
The findings of this study are consistent with previous research, providing further evidence that grain-free diets are associated with a lower mortality, reversible form of DCM, which in turn is associated with improved outcomes following diagnosis. This study does not provide insight to the exact etiology of this observation, but reinforces the need for continued investigation. The authors acknowledge several limitations, including small sample size, and encourage further research.
Summary of Data:
67 dogs met the inclusion criteria, 43 eating GF and 24 eating GI.
23 breeds were represented, 19 in the GF group and 11 in the GI group
Great Danes, Dobermans, and Labrador Retrievers were most represented in both groups, 18/43 (42%) in GF and 16/24 (67%) in GI.
Age varied significantly between groups, with GF median age of 6 years and GI median age of 9 years
21/43 (49%) GF dogs died and 19/24 (79%) GI dogs died during the study period.
The effect of diet on survival was not statistically significant when considered overall
Survival was also assessed in the context of dogs that lived at least 8 days following initial diagnosis, to consider the impact of treatment therapy on dogs that lived to undergo it.
For these dogs, previous diet was significantly associated with survival, with pGF dogs that switched diet having better outcomes than dogs eating GI at time of diagnosis
Within this group of dogs that survived at least one week, median survival time was 465 days for pGF and 263 days for GI.
Consuming GF diet for a longer time prior to diagnosis was associated with greater mortality (risk of death).
On average, pGF dogs reduced medication doses over time while GI dogs increased or maintained medication doses over time.
There was a significantly greater decrease in LVIDdN (diameter of the left ventricle of the heart) over time in the twenty six pGF dogs re-evaluated when compared to the seven GI dogs re-evaluated.
This question list is compiled based on common objections/questions surrounding the FDA's investigation into DCM in atypical breeds in association with grain-free/high-pulse diets. The information provided comes from my personal knowledge background as a veterinary student, conversations I have had with cardiologists, nutritionists, and veterinarians close to the subject, public interviews or statements from experts, and published academic literature on the topic, the latter two linked where referenced or at the end. If you have any questions or input, please use the contact form to the right, the comment section of the post, or email info@docofalltrades.net
This is intended to be educational only. If you have questions or concerns about your pet's health, please contact your veterinarian to schedule an examination.
Use the table of contents below to jump to a specific topic. You can also share this Q+A via the weblink or on Facebook. You can copy the link url from any of the questions below to link someone directly to that specific part of the Q&A.
It's a common misconception that "this was all incited by a nutritionist trying to defend the waning sales of big pet food companies as grain-free diets skyrocketed." No part of this claim actually follows. This investigation was announced to the public in 2018, but cardiologists had been in contact with the FDA for several years prior to discuss atypical cases of DCM that they were diagnosing, with an apparent common factor in diet. The incitement of this investigation was discussed in The Washington Post and New York Times. Each story provides some insight into the various cases cardiologists across the USA were seeing that prompted contact with the FDA.
The confusion with the involvement of nutritionists likely comes from a commentary published in JAVMA co-authored by Dr. Lisa Freeman, a veterinary nutritionist, and several colleagues. This commentary was published after the FDA's public announcement and was intended to review historical knowledge of diet-associated DCM and recap the (limited) information we had so far on the emerging issue being investigated by the FDA. In addition, it sought to alert veterinary professionals to a potential issue and encourage vigilance. In no way did this piece broadly condemn certain diets as an absolute cause for the issues being seen. The summary read (emphasis added):
"Pet food marketing has outpaced the science, and owners are not always making healthy, science-based decisions even though they want to do the best for their pets. The recent cases of possible diet-associated DCM are obviously concerning and warrant vigilance within the veterinary and research communities. Importantly, although there appears to be an association between DCM and feeding BEG, vegetarian, vegan, or home-prepared diets in dogs, a cause-and-effect relationship has not been proven, and other factors may be equally or more important. Assessing diet history in all patients can help to identify diet-related cardiac diseases as early as possible and can help identify the cause and, potentially, best treatment for diet-associated DCM in dogs."
This was published in 2018, and now in the face of continued caseloads and emerging findings, researchers still, in some cases even more strongly than ever, believe that there is a strong risk factor for the development of DCM secondary to certain diets. However, it is clear that this 2018 piece in no way claimed any kind of certainty.
Dr. Freeman does have several disclosures listed. This is not unusual. As a nutritionist, her job inherently involves working with the manufacturers of pet foods to ensure quality and safety for companion animals. As a specialist and as someone in academia, she is sought for speaking engagements. Disclosure of potential conflicts is an ethical standard in scientific publications, and is considered an act of transparency. Previously speaking for a company or receiving a research donation from them does not mean that one is beholden to that company to defend or exonerate them. While disclosures should always be reviewed and considered in their context as a source of potential bias, and while sometimes that bias reveals itself, such real or perceived conflicts do not inherently invalidate research or commentary.
Even still, several major brands manufacture and sell grain-free diets (such as Purina and Hill's). These major brands also have not experienced catastrophic loss of market share to boutique brands. The insinuation that they would feel so threatened by smaller manufacturers that they would craft an elaborate conspiracy involving a federal agency investigation into the death and illness of dogs rather than just shifting course on their own marketing strategies is, for lack of a better word, absurd.
Unfortunately, this issue has not been free from the influence of politics, industry, or bias. Pet food is a huge, profitable industry, and so is pulse legume farming. Some aspects of both industries have been threatened by the investigation at hand, in the loss of grain-free sales as reported by Pet Food Industry, and the subsequent estimated loss of pulse legume profits. Pulse grower associations have donated funds to research that they believe will vindicate their crops. Highly implicated brands have invested in disinformation campaigns downplaying this issue. A group of senators wrote to the FDA about being careful of the impact of their words, noting that the investigation was of significant interest to several groups of people, including farmers in their states.
Dr. Solomon, Director of the FDA's Center for Veterinary Medicine, has acknowledged the need to tread carefully in the face of this pushback: "Although CVM’s investigation must be driven by science and our public health mission, we are acutely aware that promoting transparency and public awareness may not be kind to everyone’s bottom line."
It's very telling that within the two 'camps' of thought ('yes diet is an issue' vs 'no this is blown out of proportion'), the loudest objections are coming from those directly involved in the industry as it pertains to the formulation and sale of non-traditional diets. We shouldn't ignore that some profits are hurting, but ultimately investigation must be driven by good faith desires to understand the underlying issue in the interest of companion animal health and welfare, even if that means some businesses may be harmed.
The FDA's most recent update reaffirmed that diet remains a potential factor, despite multiple industry news outlets claiming otherwise. VIN News Service has contacted the FDA directly to clarify this. The actual update from the FDA can be accessed by the public, as well as a new Q+A on their investigation. Excerpts include (emphasis added):
"If there is one point I want to drive home, it’s that the best thing you as a pet owner can do is to talk to your veterinarian about your dog’s dietary needs based on their health and medical history."
"Our veterinarians, animal nutritionists, epidemiologists and pathologists have been working with veterinary cardiologists and nutritionists from academia, industry and private practice to better understand the clinical presentation of the cases and potential ties to diet, such as bioavailability of critical nutrients and how well a dog digests these nutrients."
"As we look further into the role that diet may play in these cases, we hope to explore additional avenues of inquiry such as formulation, nutrient bioavailability, ingredient sourcing, and diet processing to determine if there are any common factors."
Less than a year ago, a headline began to circulate that '150+ studies find no link between diet and DCM.' The problem: most ofthose studies were not looking for or evaluating such a link! Of the 150+ cited sources, only FOUR are actual studies on the current issue of DCM and grain-free/legume-rich/non-traditional/BEG diets. Two are literature reviews on the current issue. Three represent different iterations of the FDA investigation. Only a handful more pertain to (different types of) diet-associated DCM at all. The majority are on other forms of DCM, and a handful don't pertain to DCM and dogs at all.
This literature review has been widely criticized by veterinarians, including cardiologists in a VIN News piece and by 'SkeptVet' Dr. Brennan McKenzie in a piece for Veterinary Practice News. Emily Brill with The Canine Review also investigated and reported on the underlying conflicts and controversy surrounding this literature review.
To summarize a few issues: Study authors omitted discussion on the significance of observed reversal of DCM in dogs following diet change. They mischaracterized the need for medical recommendations in the presence of clinical observations, regardless of the status of ongoing research. The study authors disclosed no conflict of interest, despite that four of the five work for the consulting group that formulates for Zignature, the second-most frequently named brand in the FDA update. One is even named as Zignature’s veterinarian on staff. The conclusions claim that there is no association between DCM and diet, despite the fact that correlation very much presents itself as a 'link.' Ultimately, the literature review is a misleading opinion piece that discussed mostly unrelated literature to come to an unjustified conclusion that leaves pet owners and other interested parties less informed than they would otherwise be.
DCM most commonly occurs in two specific breeds: Doberman Pinschers and Great Danes. A few other breeds are classically considered predisposed as well; Portuguese Water Dogs experience a specific and unique juvenile form of the disease. Boxers are prone to 'Boxer Cardiomyopathy,' medically known as Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC). This disease can mimic the appearance DCM or occur simultaneously with it. At least one family of Dalmatians have been documented to experience low-protein diet-associated DCM. Taurine-deficient DCM has been documented in a family of Golden Retrievers. Cocker Spaniels have also been associated with taurine-deficient DCM. In general, larger and giant breed dogs are more likely to experience DCM than smaller breed dogs, which are more likely to experience mitral valve heart disease. DCM is the 'second most common cardiomyopathy in dogs," but still only represents about 10%. Mitral valve disease represents a whopping ~75% of canine heart disease in the US.
DCM is more common in certain breeds, and genetic markers have been identified for some breeds, but it is not exclusively a genetic disease. DCM can be 'primary' (directly related to the heart, as in genetic conditions that certain breeds are predisposed to) or 'secondary'(directly related to something other than the heart, such as a toxin, an infectious disease, a nutrient deficiency, or an endocrine disease).
Primary DCM is a progressive condition that can be improved and slowed with medications, but cannot be reversed in the sense that the dog can be weaned off of medications and return to normal cardiovascular function. However, secondary DCM can sometimes be reversed and 'cured,' such that medications can be discontinued and heart parameters can return to normal, or almost normal, values. This usually requires that the underlying cause be addressed before irreversible damage has been done to the heart tissues. Double board certified specialist Dr. Sherry Sanderson, Internist and Nutritionist, has discussed primary vs secondary DCM in a podcast interview with Down With Dogs.
To bring this all around to the FDA's investigation, there are two important considerations: That the entire investigation began due to cardiologists sounding the alarm over non-predisposed breeds presenting with DCM, and dogs predisposed to primary DCM can also develop secondary DCM. The two conditions are not mutually exclusive. In fact, the FDA has discussed recovery seen in two Dobermans that saw reversal of their disease process upon switching diet. These dogs may still develop and succumb to primary DCM. But that they improved with a therapy change suggests that they had a secondary form of the disease. Geneticist and Veterinary Cardiologist Dr. Joshua Stern has discussed genetic DCM in the context of diet-associated DCM cases in several webinars. While these were not recorded for public access, Dr. Stern is continuing to research diet-associated DCM and still does not believe genetics to be the primary underlying cause for these cases.
The FDA 2019 data includes 59 classically predisposed dogs (Doberman, Dane, Boxer, and Mastiff), 95 Golden Retrievers (which are not predisposed to heart disease but may be more susceptible to nutritionally-mediated DCM), 75 mixed or unknown breeds, 86 large breed dogs (Labrador Retriever, German Shepherd, German Shorthaired Pointer, Weimaraner, Standard Poodle), and 59 medium or small breed dogs (Pit bull, Aussie, Sheltie, American Bulldog, Bulldog, and Shih Tzu). Dogs as young as five months and dogs as old as 16 years have been reported. Dogs as small as 4 pounds and as large as 212 pounds have been reported. All breeds, ages, and sizes are represented. This is not likely to be attributable to an underlying genetic condition. The FDA has dubbed these cases "non-hereditary DCM." DCM is sometimes a genetic disease, but these cases under investigation do not appear to be genetic in origin.
There are a number of other factors that have been discussed and investigated as a potential underlying cause. The potential for other factors has not been ignored. However, diet remains the single most common denominator among reported cases. This is along with a disproportionately high number of cases from diets with relatively low market shares. This trend would not be expected from chance. It also would not be expected if the underlying cause were something like vaccines, flea and tick medications, or environmental pesticides-- these factors would impact the general dog population as a whole, and we would expect reported cases to mimic market trends in terms of diet being consumed. Additionally, a trend would likely emerge, and be noticed by clinicians, where dogs presenting with illness were recently vaccinated with a specific vaccine, recently put on a specific flea medication, or recently exposed to a new yard pesticide. Instead, what clinicians have observed is a trend with a specific diet type-- grain-free or legume-rich.
Other known causes of DCM include tick-borne illness and severe unmanaged hypothyroidism. In the 2019 update provided by FDA's Vet-LIRN, they reported that 18 dogs had a history of hypothyroidism and 17 dogs had a tick-borne disease. These causes are being explored, but are not turning up answers. In the Kansas State Forum presentation, the FDA showed a diagram comparing the geographic distribution of tick-borne illness and of the reported cases. This comparison did not suggest a strong correlation with regions of high tick-borne disease levels.
Researchers continue to investigate a variety of potential causes. Up to this point, diet remains the most consistently identified common factor.
The FDA has stated that "DCM is a complex medical condition that may be affected by the interplay of multiple factors such as genetics, underlying medical conditions, and diet." This statement, while true, also applies to virtually anything in medicine. Biological systems are complex, and it may be centuries before we fully understand all the nuance underlying them. However, that does not preclude recognizing avoidable factors that cause a substantial increase in lifetime risk of certain diseases. Cancer is a complex umbrella of medical conditions that are affected by the interplay of many factors, including genetics, diet, and environment. Despite the complexity of these processes, we still acknowledge risk factors, such as exposure to carcinogenic compounds.
Since many of the dogs that recover are on medications, doesn't that mean diet change has nothing to do with improvement? It's a common question, and one with a very simple answer: cardiac medications improve function and treat heart disease, to reduce symptoms, slow the progression of disease, increase patient comfort, and extend patient life, but they do not cure heart disease. What that means is that typically, a dog started on cardiac medications will be on those medications for life and will experience some degree of disease progression over time, even if they show initial improvements secondary to medication administration. However, what is being seen in dogs that switch diets and start cardiac meds is substantial improvement up to complete reversal of heart disease. Additionally, some of these dogs are able to wean off of their cardiac medications and return to being clinically normal. This is not typically seen with heart disease, and there are very many dogs that receive these medications as part of routine therapy for heart disease. The only apparent explanation is change of diet. In previously documented nutritional DCM cases, diet and nutritional supplementation alone was shown to be sufficient for curative reversal of the disease.
To go more in depth... Administration of pimobendan has not resulted in complete discontinuation of medical therapy for CHF in any published clinical trials. The outcomes of dogs on pimobendan in clinical trials do not suggest that DCM improves to such a degree that medical therapy will be stopped or echocardiographic measures will normalize. Reduction of echocardiographic measurements is not the same as a complete resolution of clinical signs and echocardiographic evidence of cardiomyopathy, the latter of which is being reported in the cases in question. Pimobendan does not “cure” DCM, and yet dogs in cases reported to the FDA are showing a complete recovery from the disease. It is unlikely attributable to the administration of pimobendan as a primary factor.
Taurine is, generally speaking, documented to produce a positive inotropic effect, but it isn’t considered standard of care for DCM of genetic origin. There is no data that documents such a significant positive inotropic response in dogs with DCM supplemented with taurine alone, in the absence of a taurine deficiency. While taurine may improve some parameters, and dogs with DCM may benefit clinically from administration, much like pimobendan, it does not “cure” DCM (unless the DCM is secondary to taurine deficiency).
To pull this all together… administration of medical therapies like pimobendan and taurine alongside a diet change can be confounding variables, but they also appear to be unlikely contenders for standing alone as explanations for the observed disease resolution. The presence of these variables does not invalidate or undermine the importance of the role of diet in the etiology of this disease. Providing the best medical care for these animals is the ethical responsibility of a clinician, even if that reduces the research value of case evaluations.
The FDA made the public aware of this investigation in 2018, and now in 2021 we still have many more questions than answers. Even research done independently from the FDA has not offered a clear underlying cause and mechanism. This is understandably frustrating to pet owners, and truly, any member of the public or industry without a background in research. The unfortunate reality is that these things take time, especially with limited funding or ethical concerns. For example, doing clinical trials on dogs to determine if certain diets induce heart disease would entail trying to induce heart disease in said dogs. When using client-owned animals for prospective studies, it can be difficult to control variables without compromising patient care (for example, withholding taurine supplements or heart medications or not recommending a diet change). It is unsurprising, albeit frustrating, that we don't have a definitive answer yet-- and the truth is, we may never have the rock-solid, air-tight 'proof' that some are looking for. Most recently (August 2021) researchers may have identified several avenues for future research to hone in on a specific cause and mechanism.
To best illustrate how this compares to other situations, we can look to the (ongoing) 2007 FDA Jerky Investigation, the long-known but poorly-understood association between grapes and canine renal failure, and finally, the link between tobacco and lung cancer.
In 2007, the FDA began receiving and collecting reports of illness associated with jerky treats marketed for pets. Between 2007 and the end of 2015, they collected over 5000 complaints involving over 6000 dogs, over 1000 of them deaths. A variety of adverse events have been reported, including GI distress, elevation of liver enzymes, and renal or urinary dysfunction. Most striking has been 'Fanconi-like syndrome' or FLS, a loss of certain nutrients in the urine that is typically seen only in specific breeds with a genetic predisposition, such as basenjis. Removal of the jerky treats from the pets diet has resulted in improvement alongside appropriate medical treatment.
The FDA has tested these treats and to this day has not uncovered an underlying cause for these observations. They have tested for bacteria, metal contaminants, irradiation, pesticides, antibiotics, antivirals, mold and related toxins, rodenticides, known kidney toxins such as melamine, and a variety of other toxins.
The FDA has explained some of their challenges in undercovering an underlying cause to these cases:
"In human illness outbreaks caused by foodborne bacteria or contaminants, FDA works in concert with the Centers for Disease Control and Prevention (CDC) and state boards of health, which collect and track cases of foodborne illness. Unfortunately, there is no equivalent for pets, which means that it is difficult to accurately evaluate the scope of an outbreak."
"Very little is known about the possible causes for non-genetically related (acquired) Fanconi Syndrome cases in dogs, but certain toxins, medications and infections have been linked to its development in dogs and people."
"When a person dies unexpectedly, it is not unusual for a medical examiner to perform an autopsy to try to determine the cause of death. When a pet dies, it is much less likely that qualified veterinary pathologists will have the opportunity to examine the body. By the time FDA receives reports of deaths in pets, the body often has already been cremated or buried, eliminating the chance for scientists to gather more information about potential causes for the pet’s illness. "
"Finally, FDA has limited access to market data about food items for pets. FDA regulations do not require product registration for foods, whether they are intended for people or animals. "
Many of these challenges and limitations can easily apply to the DCM investigation as well.
As early as 1998, an association was noted by veterinarians between acute kidney failure in dogs and recent ingestion of grapes or raisins. In 2001, these concerns were voiced in a JAVMA Letter to the Editor. To this day, the toxic principle underlying this observation remains unknown. Not all dogs that ingest grapes experience signs of toxicosis, and a toxic dose has not been determined. Update: In March 2021, the reason for grape toxicity may have finally been uncovered.
Despite not understanding the pathophysiology of these observations, ingestion of any amount of grapes in any size dog is treated as a medical emergency by veterinarians and pet poison control centers, including recommendations for a medical professional to safely induce vomiting where indicated, collect baseline blood values and perform serial rechecks, and run IV fluids. Grapes and raisins are not necessary for the health of dogs, and with no way to predict which dogs will experience an adverse event, the safest approach is to treat every exposure as potentially deadly and provide medical intervention as such.
This example is not related to dogs or veterinary medicine, but instead helps to illustrate the scientific process within healthcare fields.
Like many fad products adopted throughout history, early tobacco use in Europe was associated with a variety of spurious health claims, from reducing anxiety to curing headaches, toothaches, and arthritis. It was the panacea. Popularized in the 19th century by soldiers in WWI, cigarettes became a preferred form of tobacco use. It wasn't until the beginning of the 20th century that scientists observed lung cancer was becoming more common. In 1950, four retrospective studies were published detailing lung cancer patient's smoking history. At this time, there was still debate over whether the perceived increase in lung cancer was real, or an artifact secondary to improved awareness and diagnosis. In one paper, the authors write that the evidence is based 'upon clinical experience and records,' and 'none of these small-scale inquiries can be accepted as conclusive, but they all point in the same direction.' In another, authors write "There is strong circumstantial evidence that cigarette smoking was an etiologic [causative] factor in cancer of the respiratory tract."
Despite the emerging evidence that had swayed the researcher's positions on the subject, it wasn't until seven years later that the US public health service issued a statement on lung cancer being caused by smoking. A January 1964 report from the Surgeon General contained the following excerpts:
"Few medical questions have stirred such public interest or created more scientific debate than the tobacco - health controversy . The interrelationships of smoking and health undoubtedly are complex . The subject does not lend itself to easy answers . Nevertheless , it has been increasingly apparent that answers must be found ."
"It is not feasible to submit human beings to experiments that might produce cancers or other serious damage , or to expose them to possibly noxious agents over the prolonged periods under strictly controlled conditions that would be necessary for a valid test . Therefore , the main evidence of the effects of smoking and other uses of tobacco upon the health of human beings has been secured through clinical and pathological observations of conditions occurring in men , women and children in the course of their lives , and by the application of epidemiological and statistical methods by which a vast array of information has been assembled and analyzed."
"Among the epidemiological methods which have been used in attempts to determine whether smoking and other uses of tobacco affect the health of man , two types have been particularly useful and have furnished information of the greatest value for the work of this Committee . These are ( 1 ) retrospective studies which deal with data from the personal histories and medical and mortality records of human individuals in groups ; and ( 2 ) prospective studies , in which men and women are chosen randomly or from some special group , such as a profession, and are followed from the time of their entry into the study for an indefinite period , or until they die or are lost on account of other events ."
Today, there is little controversy surrounding the claim that smoking cigarettes is a very prominent risk factor in the development of a wide variety of diseases and illness. While we have had decades to put together the breadth of knowledge informing this belief, research pertaining directly to the effects of tobacco on humans does still come primarily from retrospective and prospective studies, rather than double-blind clinical trials.
For similar ethical reasons cited above, it is unlikely that such gold standard research will ever be conducted on dogs in the context of diet-associated DCM. But several retrospective analyses have contributed to discussion surrounding this disease, and several prospective studies are underway. It's easy to imagine how many lives may have been prolonged had investigation into tobacco use not taken so long to grab hold of public attention and begin to sway beliefs surrounding it. Given the nature of the diets in question, particularly their lack of necessity or health benefits, it stands to reason that avoidance until this concern is either further confirmed or laid to rest may be in the best interest of potentially prolonging companion canine lives.
The FDA's investigation into non-hereditary DCM in dogs, and all other endeavors, are funded by USA taxpayers. Every fiscal year, the FDA is provided a budget appropriation.
The ongoing research at academic institutions are funded in a variety of ways, including donations from the public. For example, a retrospective analysis on diet and DCM published recently (Freid et al. 2020) was funded by the 'Barkley Fund,' a memorial fund set up by the owners of a dog that passed from cardiac disease. Some of these studies may be funded in part by companies in the pet food industry. To quote myself from another article on this topic: One would be hard pressed to find research experts in any field who have never received financial support from companies or corporations invested in that field. For better or worse, that's the nature of our current economy. That is why it's standard to disclose such connections and important to critically evaluate methodology and obtain peer-review for any scientific studies. Processes like peer-review are in place to mitigate risk of bias, and researchers are mandated to disclose any potential financial conflicts that could be construed. Critical examination is warranted, but we cannot presume that every study partially funded by a grant from a corporation was swayed in that corporation’s favor.
There is a common misconception that the FDA "only requested cases from dogs eating a grain-free diet," therefore causing a bias in the sample pool. The original FDA request (now only available in archive) did not specifically ask for cases from dogs eating grain-free diets. It reads: "The FDA encourages pet owners and veterinary professionals to report cases of DCM in dogs suspected of having a link to diet by using the electronic Safety Reporting Portal or calling their state’s FDA Consumer Complaint Coordinators."
The reason that the FDA did not ask for reports of all cases of canine DCM is because there are instances where DCM can easily be explained by factors other than diet-- for example, an adult Doberman Pinscher with a family history of DCM. If the FDA had to sort through data on cases that veterinarians could easily determine are not likely to be dietary in origin, it would bog down the entire investigation. There are cases reported from dogs eating grain-inclusive diets. Grain-free diets just vastly outweigh them. This doesn't appear to be a coincidence or isolated sample bias-- studies have also shown an association between non-traditional diets (like grain-free) and DCM when compared directly to dogs eating more traditional diets.
It's easy to wonder if some aspect of this boils down to a trend between what types of food people purchase and how likely they are to get an illness diagnosed by a veterinarian. However, to borrow a phrase from those pushing back on this issue, consumer purchasing behaviors are complex and multi-faceted. There are many assumptions that have to be true in order for this logic to follow. Even if we accept the assumption that the amount people spend on pet food correlates with the amount they're willing or able to spend at a veterinary clinic, there are both expensive and inexpensive grain-free diets, and both expensive and inexpensive grain-inclusive diets. Even still, it would be difficult to explain away such huge disparity between market share and the overrepresentation of some of the named manufacturers with the claim that those specific people feeding that specific food are the only people that take their pets to the vet or pursue advanced imaging and diagnostics.
There are also other scenarios to consider, even if we assume that grain-free diets are 'expensive' and grain-inclusive diets are 'cheap.' For example, what if someone spends less on dog food so that they can afford emergency care or advanced diagnostics for their pet? What if someone spends so much on a dog food that they believe is best that they can't afford expensive veterinary bills? Brands like Purina Pro Plan are popular among show and sport breeders and canine sport enthusiasts. Many of these dog receive health clearances, including an echocardiogram.
There is likely no doubt that certain socioeconomic circumstances preclude a diagnosis of DCM. But we shouldn't assume that consumer buying behaviors have such a large sway over willingness to spend on veterinary bills that it explains away the disparity observed in case reports. Additionally, studies comparing dogs eating non-traditional and traditional diets have continued to identify a link between non-traditional diets and heart abnormalities. These studies don't eliminate all extraneous variables, but they do remove the assumption that dogs eating traditional diets aren't being examined for heart health.
The full scope of this issue is unknown for many reasons. Short of collecting a large random sample of dogs to be evaluated by cardiologists, we can't possibly hope to estimate how many animals are affected. DCM can exist as an occult disease, meaning the dog in question is asymptomatic. Even in dogs that have symptoms, those symptoms may be vague, non-specific, or even so subtle that they go unnoticed: decreased energy, lethargy, lowered exercise tolerance, an occasional cough. DCM can occur with arrhythmia, or abnormal heart rhythms, which are a risk factor for sudden death. Without an autopsy, which owners may not pursue for a number of reasons, that cause of death may never be determined. While not all dog owners are aware of an autopsy as an option, others lack the funds to pursue one, or elect not to in order to keep the remains of their pet. As discussed in the 'Annual Exams' section below, DCM is not something that would be picked up through routine canine healthcare. Even for owners with suspicion that their dog may be ill, there are barriers to the accessibility of veterinary cardiology services. These barriers may be geographic (no local practices), financial (specialty care is expensive), or simply the inability to make an appointment due to a high caseload seen by the relatively few cardiologists in the USA.
All of this means that the cases reported to the FDA (now >1100) are only the tip of the iceberg-- the cases that were both diagnosed and reported. Under the surface, you have an expanding base: cases diagnosed but not recorded, dogs with clinical signs that haven't been diagnosed, dogs without clinical signs that haven't been diagnosed, and dogs that died suddenly without an autopsy performed and will never be diagnosed.
Some mistakenly claim that unless 100% of dogs eating certain diets develop disease, diet is not the underlying cause of the disease process. However, many known risk factors for diseases exist that do not impact 100% of the exposed population, due to individual differences in genetics, environment, and epigenetics. For example, not 100% of people with chronic sun exposure will develop melanoma. Not 100% of people that smoke will develop lung disease. Not 100% of people with high cholesterol will develop heart disease. Biological systems are complex, and it may be centuries before we fully understand all the nuance underlying them. However, that does not preclude recognizing avoidable factors that cause a substantial increase in lifetime risk of certain diseases.
As of right now, there is no large-scale data available tracking cases of DCM seen by the ~300 cardiologists in the USA. Such data may make it easier to determine to what extent atypical breeds are presenting with this disease. However, collecting such data at the necessary scale would require the time and cooperation of dozens, if not over 100 institutions that may have no easy way of procuring it. Until such data can be collected, the reported experiences of clinicians seeing these cases should be sufficient to at least raise a flag of vigilance and concern.
Many individuals less cautious of this issue cite their annual exams with their vet as evidence of their pet's good health, despite feeding a grain-free or otherwise non-traditional diet. While annual exams are important for tracking your pet's general health over time, DCM is a disease that is not frequently revealed through standard routine diagnostics. DCM rarely causes a heart murmur that can be heard through your vet's auscultation by stethoscope. DCM may cause arrhythmias, but most dogs do not routinely get an EKG during their annual exam. Dogs with DCM may show no symptoms (occult disease). While a specific blood test, ProBNP, may suggest underlying heart disease, it is not routinely performed, and it isn't perfect. A standard blood panel would not show DCM. X-rays may show an enlarged heart, but are rarely recommended for otherwise healthy pets. An echocardiogram with a cardiologist is the only way to definitively diagnose a dog with DCM.
One reason some pet owners are reluctant to switch away from grain-free diets (or other non-traditional diets) is often cited as the very reason they started purchasing them in the first place-- the perception that they're healthier, safer, or hypoallergenic. However, there is no evidence that shows grain-free diets are associated with unique health benefits when compared to the more traditional, grain-inclusive diet formulations. Grain allergies are also incredibly rare, even as a subset of adverse food reaction which themselves are estimated to affect no more than ~10% of dogs with atopic dermatitis (itchy skin). These reactions are most commonly to chicken or beef. While grains are often reported on food allergy panels, these tests are notoriously inaccurate.
Even if a pet had a severe, broad allergies to grains (which is virtually unheard of), a commercial grain-free diet would still pose problems as cross-contamination of commercial pet foods is well documented to be an issue between formulas, with many diets containing trace amounts of undeclared proteins.
Read more on this from the Clinical Nutrition Service at Cummings School of Veterinary Medicine at Tufts.
A lot of people ask if they can just supplement taurine or add grains like boiled rice into their dog's food. There are several problems with this approach, the first and foremost being that we don't know that either of those things (insufficient taurine, or the actual absence of grains) are the underlying cause of these observations. Not all of the dogs reported to the FDA have tested low for taurine, and adding ingredients to a commercial diet runs the risk of introducing nutrient deficiencies by unbalancing the formulation. Rather than trying to fix a potentially broken diet, the safest thing to do is switch away from it until we know more. If some underlying common thread between these diets turns out to be, for example, something impairing taurine metabolism, no amount of added taurine would help unless the diet was also changed.
A common follow-up to that is confusion surrounding why many dogs are receiving taurine supplementation alongside a diet change after being diagnosed. In the simplest terms, this is being done just in case it helps expedite recovery. The recovery itself is still strongly thought to be predicated on the diet change itself.
Many of the researchers investigating this issue believe the underlying cause to ultimately be one of poor formulation, not necessarily the inclusion of exclusion of any particular ingredients alone. That said, out of an abundance of caution, it may be best to avoid diets from any manufacturers with a significant number of case reports/complaints, even if the specific diets of interest are grain-inclusive, until more information is available. Grain-free diets or diets high in pulse legumes such as peas, chickpeas, or lentils, may also be worth avoiding, particularly in the absence of medical indication to feed such as diet. The next section contains some suggestions for considerations to have when evaluating pet foods. UC Davis has published guidelines as well: "While avoiding all suspect ingredients may be the most direct way to select a new diet, we suggest that a small amount of
legume content in a well-formulated grain-inclusive diet may be OK. Our guidelines allow for no more than two legume
ingredients in a grain-inclusive diet when found low on the ingredient list (below all meat and grain content). Importantly, these
diets should still be tested by AAFCO feeding trial."
The World Small Animal Veterinary Association has put together a list of recommended questions to ask a pet food manufacturer when deciding on what to buy. These questions aren't comprehensive, and WSAVA doesn't advise how you should expect a company to answer, but they are a good place to start. Some people have criticized certain standards as being prohibitive to smaller companies. However, if a company cannot afford bare minimum standards for formulation and production quality, they should not be manufacturing dog food. Using the WSAVA recommendations and the advice of several veterinary nutritionists, here is what you should look for:
1. Companies should employ at least one, dedicated full-time nutritionist, and ideally, they should have several. This would be someone with a PhD in animal nutrition or a veterinarian boarded in nutrition as a specialty (DACVN). Some companies will state they 'work closely with nutritionists' or 'consult with a nutritionist.' While these are good practices, a consultant cannot provide the same level of dedicated and detailed oversight to formulation and product management as a full-time employee, or team of employees, can.
2. The diets should be formulated by someone qualified to do so- such as a veterinary nutritionist. Experience in the pet food industry, or owning dogs, regardless of how many years, does not alone qualify someone to formulate diets. Much like in the first case, a team of qualified expert professionals is even better than just one or two. In the best case scenario, there will be not only nutritionists, but food scientists and toxicologists involved as well.
3. Diets should undergo feeding trials that, at a minimum meet, and ideally exceed, AAFCO standards/protocols. In addition to feeding trials, diets should be formulated to meet nutrients profiles and undergo analysis of the finished product to confirm nutrient levels. Testing diets only for digestibility or palatability, or meeting AAFCO standards by formulation or analysis alone, is less ideal.
4. Foods should be produced in facilities owned and operated by the manufacturer so that every aspect of production can be closely monitored. Ideally, foods sold in the USA should be manufactured in the USA. These facilities must be equipped with machinery, laboratories, and staff that can provide extensive, on-site quality assurance. Manufacturers that contract with a third party facility to produce their foods lose some degree of control over quality and also risk cross contamination if there are issues that arise with other diets produced at those facilities.
5. Manufacturers should have transparent and extensive quality control protocols. This should include selection criteria for partners, analysis and sample tracking of externally sourced ingredients such as vitamin mixes, daily safety checks of product batches and facilities, physical inspection, and key nutrient testing before final packing. Some companies will save samples from each batch/lot in order to re-evaluate or investigate that diet should issues arise later. The presence of a recall history does not preclude a manufacturer having good quality control. However, the frequency with which recalls occur, the nature of the recall, and the manner in which the company proactively responds should be considered.
6. Companies should be able to provide a complete nutrient analysis for any food they produce on an energy basis (grams per kcal) and additional information such as digestibility.
7. They should have information on the caloric value for any formula readily available in kcal per gram diet and per cup.
8. Companies should be investing in and conducting nutrition research that is relevant to the diets they are putting out onto the market, particularly when making health claims or introducing a novel formula that strays from traditional or well-researched norms. This research should be peer-reviewed and published. It is a red flag for a company to claim research as 'proprietary' and unavailable for review. Companies that do not engage in any research endeavors, or worse, actively oppose nutrition research, may be best avoided.
Published in the Journal of Veterinary Internal Medicine, a retrospective analysis has again affirmed a link between certain diet types and dilated cardiomyopathy. Among the authors is Dr. Lisa Freeman, a veterinary nutritionist who has been closely working on this emerging issue since it was brought to public attention in 2018. This study was funded by Tufts' "Barkley Fund," established by the owners of a late Great Dane to further support and promote ever-improving care for dogs with heart disease. As a retrospective study, this paper has numerous limitations that the authors acknowledge. Furthermore, it does not establish a definitive causal relationship between diet and the development of DCM. Scientific establishment of such a causal relationship, if it exists, will require findings from the ongoing prospective studies that are occurring at multiple institutions. In the meantime, a correlation between diet types and DCM continues to be identified, warranting vigilance from the veterinary community, pet owners, and the pet food industry.
The study is open access, meaning that anyone can read it online for free! You can use the hyperlink above to open it yourself. While the paper is accessible in terms of being free to read, the language of an academic paper can be intimidating for people outside of the field or profession. Here are the important highlights for pet owners and other concerned members of the public:
Methods & Sample:
This study collected and analyzed records from dogs seen at the Tufts veterinary hospital by the cardiology or nutrition service and newly diagnosed with DCM between 2014 and 2018.
Dogs were grouped by traditional and non-traditional diet, as well as whether or not they changed diet following diagnosis
Traditional diets (TD) were grain-inclusive extruded (kibble) diets that did not contain peas/lentils/potatoes in the to 10 ingredients and are produced by manufacturers that meet the WSAVA recommendations for selecting a pet food
Non-traditional diets (NTD) were grain-free, contained peas/lentils/potatoes in the top 10 ingredients, or are not produced by manufacturers that meet the WSAVA recommendations for selecting a pet food
71 dogs were included
56 were eating NTD at time of diagnosis and 15 were eating TD
18 breeds were represented total
Findings:
Among dogs eating non-traditional diets, those that changed diet had a significantly longer average survival time (337 days) than those that did not (215 days).
Functional cardiac improvement was seen in dogs eating a NTD at time of diagnosis that switched to a TD.
The number of dogs diagnosed with DCM at this specific hospital has increased over time.
The authors close the paper: "Our results are consistent with the results of 2 previous studies suggesting that in dogs with DCM eating nontraditional diets, diet change can be associated with significant improvement in some echocardiographic measurements. In addition, dogs eating nontraditional diets that had their diets changed had a significantly longer survival time compared with those that did not have their diets changed. The underlying cause and mechanisms of diet‐associated DCM are still not understood, but our findings emphasize the importance of prospective studies to better understand this issue as soon as possible."
This piece should be prefaced by saying that PLOS One's commitment to transparency and diligence in maintaining scientific integrity is commendable. Their timeline in following-up on this particular issue, however, is disappointing and has left many pet owners confused. In May 2020, new research was published evaluating correlation between diet types and heart size parameters in Golden Retriever. This research had an 'Expression of Concern' added to it four months later, in September:
"The article is being reassessed in light of issues raised post-publication, and the journal is investigating the validity of the concerns raised as well as their implications for the reliability of the article’s conclusions. Meanwhile, the PLOS ONE Editors issue this Expression of Concern."
Now three months later, no additional updates have been issued. While the PLOS ONE editors explicitly stated that the very validity of the raised concerns was under investigation, this addition has not stopped various parties from using this Expression to delegitimize the research and dismiss the concerns surrounding grain-free and boutique diets. In the interest in providing a balanced narrative, each concern should be individually examined. It is imperative that the conversation not be dominated by misplaced dissent. The current study provides one more piece to the
puzzle, and will hopefully not find itself unduly compromised by an unreasonable expectation of perfection.
The possible origin of the alleged concerns is worthy of note. They closely mirror those presented in a Pet Food Industry article authored by Dr. Ryan Yamka, PhD, owner of a pet food consulting group and co-founder of Guardian Pet Foods. At the end of his article, Dr. Yamka indicates he had written to PLOS, and he includes a reference number for his case: 06641324. He welcomes readers to cite it if they decide to follow suit and write a letter themselves. The concerns published by PLOS One are as follows.
"Questions were raised around the criteria used to categorize diets, including about the rationale of including global company sales details in these criteria given the objectives of the study."
The rationale for the criteria used was explained extensively by the authors in the
‘Materials and Methods,’ section as well as the ‘Discussion.’ Guided by clinical experience as
well as the previous findings from the FDA’s preliminary report , the authors defined the
categories on the basis of pulse legume content (represented in 93% of cases reported to the
FDA), absence of grains (represented in 91% of cases reported to the FDA), and manufacturer
size (inversely correlated with prevalence of case reports). The decision to use global company
sales as a criteria, which was of particular interest in the expressed concern, has a precedent in
earlier commercial pet food research, namely a 2014 study in JAVMA that assessed thiamine
concentrations in canned cat foods. That study utilized the same criteria and did find a
significant difference in thiamine concentration in foods produced by smaller companies. To
further characterize the rationale for including sales as a criteria, it is helpful to closely assess
the data reported from the FDA in the context of the annual revenue of those companies. As
the authors of the current study noted, there appears to be an inverse relationship between the
number of cases reported to the FDA and market share held by the manufacturing companies.
In the June 2019 update, the FDA’s update included a graph representing brands with ten or
more reports associated, totaling 431 reports. Of those 16 brands, 8 brands associated with 236
reports are produced by companies with less than $1 billion annual revenue, 4 brands
associated with 145 reports are produced by companies with between $1 and $2 billion, and the
remaining 4 brands associated with 50 reports are produced by companies with greater than $2
billion. Further evaluation of those 4 brands from the largest companies also supports
the trend. While Nutro and California Natural are owned by Mars Pet Care, their individual sales
are each less than $1 billion of the company’s $18 billion revenue. Given the study’s objectives,
which included evaluation of differences in taurine and echocardiographic parameters in
association with diet in light of the FDA’s investigation, these criteria are entirely justified.
"Concerns were raised about potential confounds in the study, for example due to the inclusion of adult, puppy, and prescription-only foods, and due to inclusion of raw and kibble diets in the non-traditional group whereas the traditional group only included kibble"
While an argument could be made that exclusion of raw diets would have been more
appropriate, it is expected that if they were included, they would not be included with traditional
diets, because they are not traditional. Commercially available raw diets are a relatively modern development. Raw diets have been reported to the FDA in associated with development of DCM. That said, many dogs are fed combination diets, and it’s likely that many of the
dogs consuming raw foods were also consuming kibble diets in conjunction. While this presents
a limitation to the study (and indeed, was discussed as a limitation by the authors), it does not
invalidate the findings nor render them less useful. Further studies could better elucidate the
differences between non-traditional kibble alone, raw alone, and combination diets of both. The
inclusion of puppy food only pertained to two diets included in the sample, and one of those was
labeled for all life stages. The prescription diets also meet the criteria for ‘traditional diets’ and
are labeled as complete and balanced adult maintenance diets per AAFCO feeding trials. As the
diets in question still met the criteria outlined for the purposes of the study, it isn’t problematic
that they were included. Furthermore, their exclusion likely would not change the results and
conclusions, as they represent such a small portion of the sample size. This study was
concerned with overarching data trends, not individual points of data. The sample groups
represent real dogs presented to the clinic for wellness checks. While these criticisms would be
warranted for a randomized double-blind laboratory controlled study, applying them toward a
study of this nature, a case-controlled study on publicly owned animals, is misplaced.
"Soybeans are in the legume family, but soybeans and soy products were not considered as legumes for the purpose of categorizing diets in this study. The authors have requested a correction to clarify that this was an intentional exclusion, and they have noted that this aspect of the study design aligned with how soy products are being handled in a related FDA investigation."
The authors adequately addressed this concern.
"Questions were raised about the statistical analyses reported in the article."
The current study utilized typical, widely employed statistical analyses.
This included not only the data means, standard deviations, and p-testing (null hypothesis
significance testing) but also appropriate, more specific analyses: Fisher’s exact test and Spearman’s
Rank-order correlation evaluation. Fisher’s exact test, which is intended to examine significant
association between two different categories of data, was used appropriately to assess
statistical associations with clinical findings between the diet groups. Spearman’s Rank-order
correlation evaluation, which assesses two ranked variables for the strength and direction of an
association between them, was used appropriately for evaluating correlation between diet
groups and taurine levels.
One of the publicly offered criticisms of the current study was the failure to employ
‘proximate component analysis.' The exact meaning of this statement is difficult to parse out.
‘Proximate component analysis’ typically refers to the percent make-up of various nutrients in a
given formulation. If this was the intended meaning, this type of analysis would have been
inappropriate for the current study, though it could prove useful for future investigations.
Alternatively, the author of the criticism may have meant ‘principal component analysis,’ or even
‘factor analysis,’ which is commonly confused with the former. Both of those methods seek
to reduce the number of variables in a given data set, albeit through differing means. In any
case, while the goal of the present study was to determine if there are differences in the
assessed clinical parameters (taurine and echocardiographic findings) between two broad
categories of food, a future study seeking to further hone in on specific aspects associated with
the differences within one of the broad diet groups could benefit from additional statistical
analyses.
"Reporting errors were noted, including errors in Tables 1 and 2, for which the authors requested a correction, and other issues raised to the journal that may impact categorization of some included foods as traditional versus non-traditional."
It may be fair to remove some included foods and request that the authors issue a
correction to their data. Based on the public issue of these concerns, not all of the issues
raised are as significant as others. For example, while a diet with traits that fit both the TD and
NTD groups may be fair to omit, such an omission would be unlikely to influence the overall
data trend, since the dog eating the diet in question did not have abnormal parameters. In fact,
it’s possible that exclusion of this diet would strengthen the significance of the author’s findings,
since it was included in the NTD group. However, concerns raised about a mistake in naming a
diet (listed as a partially pork formulation, when that company does not produce a pork diet) are almost certainly secondary to a mistake in the owner's reporting of diet history, and while such inconsistencies should be investigated
and clarified, it is very unlikely such an error would compromise the study, the data, or the conclusions. The protein source was not evaluated as part of this study. Concerns about the classification of Merrick based on their acquisition by Nestle Purina are also
misplaced. While Merrick is owned by Nestle Purina PetCare, a public statement has been
issued that they continue to operate independently, with no changes at the hands of Purina
secondary to the transaction.
"Questions were raised as to whether three months on a given diet is a sufficient duration to impact cardiac/DCM outcomes, and whether diet history prior to a subject’s current diet may impact the study outcomes. Concerns were also raised about differences between groups in the average time on the current diet."
This was discussed extensively as a limitation by the study authors. Namely, while it
represents a limitation for the evaluation of the echocardiographic parameters and should be
considered for future studies, it is not expected to impact the taurine analysis, based on prior knowledge that changes in taurine can occur in a matter of weeks, which is well within the three
month (12 week) minimum period. The length of time on a certain diet, and the impact of
prior diet history on findings, is a limitation not just to this current study, but to analysis of
publicly owned animals as a whole. While it is significant that the average length of time on a
given diet was nearly twice that for dogs in the NTD group when compared to the TD group, this
may simply reflect consumer behavior differences between the owners that are most likely to feed each.
Assessment in this area would best be explored in a randomized clinical trial with a population
of laboratory animals. Given the investments necessary to conduct a study of that nature, in
terms of both time and finances, it would be unreasonable to discount more feasible research
on the basis of that limitation alone. These differences are something to consider when
evaluating the data, but not something which invalidates the data or subsequent findings.
"Questions were raised about the validity of the conclusion statement, “Grain free diets, produced by small companies, including legumes within the top 5 ingredients represent a risk for the development of taurine deficiency and echocardiographic abnormalities consistent with DCM in the golden retriever.”"
Given that the questions surrounding the validity of the conclusions likely arise from the
concerns stated above, it is fair to say that the conclusions remain valid in light of the concerns
being misplaced. In medicine, a risk factor is something associated with an increased chance of
developing a disease. The findings of the present study are consistent with a correlation
between the consumption of NTD (grain-free, small company, containing legumes in the top 5
ingredients) and clinical traits associated with disease. That correlation represents a risk factor.
________________________________________
While PLOS One is doing the responsible thing in transparently responding to received
concerns, investigating the validity of said concerns, and reassessing the paper in light of them,
that these illegitimate concerns were received at all illustrates one more example of what has
become a concerning trend of industry pushback to researching this topic. There should be no
question that the industry has been negatively impacted by this investigation, with market trends
showing that consumers are drifting away from grain-free varieties of food. What has
become problematic is that rather than proactively seeking to identify the underlying cause and
change formulas appropriately, the response from the industry has largely been to downplay
and minimize the importance, or even existence, of this issue. Read more here.
Most of the content in this article was originally included in a letter to the editors of PLOS One.
