Big Business and Bad Science

As many pet owners are now painfully aware, last July the FDA announced an investigation into a purported association between dilated cardiomyopathy (DCM), a deadly disease of the heart, and grain-free commercial diets. This investigation began at the behest of veterinary specialists who perceived a recent spike in cases of DCM in breeds not typically expected to develop it.

This June, the FDA released a major update, controversially providing the names of brands with 10 or more reported cases. While cases from veterinarians span back as far as 2014, the FDA states in their update“ the vast majority of the reports were submitted after the agency notified the public about the potential DCM/diet issue in July 2018.” In total, as of April 30, 2019, over 500 cases had been reported. Since that update, the situation has reached new levels of publicity, spanning across major news networks and garnering the attention of pet professionals everywhere. Amidst all this, a common thread seems to remain: conflicting information and confusion.

July of this year, a claim began circulating that poor methodology, undisclosed financial interests, and ultimately, ‘Big Pet Food,’ are behind the unwarranted attention to the issue of grain-free diets and canine DCM. In particular, question was called to the JAVMA article “Diet-Linked Dilated Cardiomyopathy: What Do We Know?” At the root of this claim lies Mr. Daniel Schulof, lawyer by trade, pet food writer by choice, and CEO of KetoNaturals pet food, a diet formulated primarily with pea protein, an ingredient implicated in 89% of the FDA’s reported cases. Citing financial damages to his company as motivation, Mr. Schulof has sent a 42 page letter to JAVMA requesting retraction of the article mentioned above. While compelling, how valid is his case? Considering his own financial interest in protecting a company that falls within the radar of DCM scrutiny, it seems worthwhile to approach the claims critically. This is a long article, so strap in.

Myth: More than 200 veterinarians, animal scientists, and ‘other stakeholders’ co-signed the retraction package to JAVMA

Only 9 veterinarians, a few of them unnamed, signed. None of them were boarded nutritionists. 3 non-veterinary animal scientists signed, 14 non-veterinary medical professionals, and 14 representatives of ‘BEG’ pet food companies. All other co-signers fell into the category ‘other.’ Some of these ‘other’ identified themselves as pet owners, dog breeders, or owners of independent pet food retail shops. The vast majority did not identify a profession or a stake.

Myth: There is actually no evidence that canine DCM is associated with ‘BEG diets,’ ‘grain-free diets,’ or any specific ingredients.

There is currently strong evidence of a correlation (or association) between certain diets, ingredients, and DCM. Research uncovering a causative link, if there is one, is currently underway. In the FDA report, 91% of the dogs were consuming grain-free diets. 93% were consuming a diet high in legumes and peas. Considering the relatively lower market share of these diet-types and ingredients in the US, such atypical numbers are undeniably a correlation. In light of that observed correlation, numerous universities across the US are now conducting research to discern what, if any, causative factors are underlying the correlation. It is worth noting that many veterinary cardiologists are reporting clinical improvements in DCM patients that change diet following diagnosis, even in the absence of other medical intervention. Reversal has also been seen in dogs reliant on heart medications that are then able to be weaned off following diet change. While it may seem reasonable to blame medications for that improvement, in genetic forms of DCM reversal is not seen, even after months of medication, as they function through supporting, not healing, the heart.

Vet-LIRN has found that only 9% of dogs had hypothyroidism (a risk factor for DCM) and just 8% had a history of tick-borne disease (with Lyme exposure also being a DCM risk factor). Heavy metal and narcotic exposures have been inquired about, and DNA samples have been collected from affected dogs to try and discern if there is a genetic component. To date, the most significant, consistent association common to the affected dogs remains diet.

Myth: Very few dogs have developed diet-mediated DCM.

The FDA explicitly states in their most recent update that for a variety of reasons, dogs are likely not just under-diagnosed, but under-reported. There are no grounds to minimize the reach of companion animals affected by this disease. DCM can progress a-symptomatically, resulting in sudden, unexplained cardiac failure and death. Unless necropsy is pursued, which can be cost-prohibitive and often entails forfeit of a beloved pet’s remains, these cases will never be known. Even when symptomatic, dogs often present with coughing, lethargy, and general malaise, non-specific signs of a myriad of different diseases. They often will auscult normally, with no heart murmur. Diagnosis requires an echocardiogram, an expensive procedure often performed only by cardiologists. Prior to this issue, it would be uncommon to screen a dog without genetic predisposition for DCM. Since the FDA’s announcement, obtaining a diagnosis has only become even more difficult, with many cardiologists booked weeks to months out. There are less than 300 veterinary cardiologists in the US, and they are not distributed evenly, creating geographic disparity in accessibility. It is nearly impossible to put a ceiling on the number of affected dogs, but for anyone who loved one of the 100+ deceased dogs reported to the FDA, even one case of diet-associated DCM is too many.

Myth: The veterinarians at the heart of the DCM investigation are financially tied and beholden to Hills, Mars, and/or Nestle-Purina.

The particular individuals under fire with this claim are Dr. Lisa Freeman, Dr. Joshua Stern, and Dr. Darcy Adin. The first contention is that they all work for research universities that receive donations from Hills, Purina, and Royal Canin. If one excludes all research out of research universities as invalid due to financial interest from corporate donations, there would be very little research left in the world. The researchers are not beholden to any of the corporations that have donated, past or present, to the university under which they are employed. More information on corporate funding is provided later in this piece.

Dr. Lisa Freeman disclosed her potential conflicts of interest in the JAVMA article. “Within the past 3 years, Dr. Freeman has received research support from Aratana Therapeutics, Nestlé Purina PetCare, and Royal Canin; has consulted with Aratana Therapeutics and Nestlé Purina PetCare; has given sponsored talks for Aratana Therapeutics, Hill’s Pet Nutrition, and Nestlé Purina PetCare; and has served on a scientific advisory board for Aratana Therapeutics.”

Dr. Adin did the same. “ Within the past 3 years, Dr. Adin has received research support from Nestlé Purina PetCare.”

These authors are not receiving an ongoing salary from these companies, nor do they necessarily stand to gain additional future funding or support if Purina or Hills or Royal Canin continue to grow as companies. 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. That is why it is standard to disclose such connections and important to critically evaluate methodology and obtain peer-review for any scientific studies.

Myth: The leading academic article about DCM, published in JAVMA, was done so under the guise of peer-review, while in fact circumventing the peer-review process entirely.

The article, published in the commentary section, was not published as a peer-reviewed study. It was not presented as a meta-analysis, does not contain an abstract, and was at no point presented as research. As a commentary, the article is an opinion piece — it presents the opinion that the potential underlying diet-mediated cardiomyopathy is concerning and warrants vigilance. It also emphasizes the opinion that marketing has outpaced the importance of evidence and science in the field of pet nutrition. The summary of the article reads (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.”

The authors made it no secret that there are significant, glaring gaps in our current knowledge. Despite that this is a commentary, however, the opinions presented were bolstered with facts, hence “What Do We Know.” The article cites 33 outside sources and clearly details what was previously known about DCM, what findings are emerging, and what concerns are now present.

Additionally, despite being published as a commentary piece that is not obligated to undergo peer review, this particular piece still may have. On the supplemental materials page corresponding to the article, the following text can be found: “ This supplementary content was made available to the external peer reviewers at the time of manuscript review.” While the text may be included in an automated error, as most commentaries do not include supplementary materials, the only way to confirm that peer-review was not undergone is to contact JAVMA directly. This article will be updated to reflect any new information on that front. Regardless, the piece underwent editorial review before publication and the nature of the content does not necessitate peer-review.

Myth: Recent studies on DCM have had serious, unaddressed methodological problems.

Recent studies on nutrition-related DCM are limited, as has been openly admitted by both advocates for the rising concern and dissenters alike, but do not have the “serious flaws” purported.

A retrospective analysis, published in Feb 2019, found differences between nutritional and genetic forms of DCM. As a retrospective analysis, this study relied on information, such as diet history, that had already been obtained as part of the clinical evaluation, before the undertaking of the studies. For reasons like this, retrospective studies are inherently limited and serve primarily to identify areas of future clinical research. The authors highlight these limitations in their discussion. Mr. Schulof’s primary contention with this study is that the final published data do not match data given in a preliminary form of the study presented during an earlier conference. He states that correspondence with Dr. Adin, one of the authors, confirmed that the reason behind the change in data was a re-evaluation of the available diet histories. This is a very common occurrence in research. Abstracts for conferences are submitted well in advance, and research papers undergo extensive editing and review before final publication. The conference itself presented an opportunity for other professionals to assess the methodology and point out an issue such as inconsistency in inclusion criteria. He discusses the odds of this occurring by chance to be “less than 1 in 10,000.” However, this decision was not made by chance, with random cases excluded without reason. The decision was made by analysis of available data against a set of inclusion criteria. The authors note “This study had several limitations inherent in its retrospective design. The presence of a detailed diet history was inconsistent in our medical records during this study period, which reduced the number of included dogs and could have introduced bias.” To be more specific, it is possible that clinicians are biased to conduct a more extensive diet history with owners feeding a grain free diet, and that bias could subsequently result in more grain-free fed dogs available for analysis retrospectively.

Contention with the second study lies in regards to the involved diets not being tested for their amino acid profiles. While it may be the case that the underlying cause of the taurine-deficiency noted was amino acid deficiency in the diet, that does not absolve grain-free or legume-containing diets of association. In fact, it would only serve to indicate that there is indeed an observable dietary deficiency in those formulations, despite being marketed as complete and balanced. Contrary to some claims, this possibility was not ignored by the authors of the paper. They clearly state: “ Ideally, amino acid concentrations in the diet, especially taurine, methionine, and cystine would be obtained to determine if diets were deficient in any of these essential ingredients. However, this data was not made available by the diet manufacturers. Further research is needed to better understand their characteristics before any additional conclusions can be drawn.”

Myth: Independent analysis has shown that sulfur-containing amino acid deficiency is to blame, not grain-free and not peas or legumes.

Mr. Schulof took it upon himself to analyze pet food formulas involved in a golden retriever study on DCM, many of which were from brands also over-represented in the FDA case reports. While his provided analysis claims low levels of methionine and cystine, the FDA’s own analysis of the foods came up different. Dr. Jennifer Jones with Vet-LIRN at the FDA stated that of the tests conducted on involved dog foods collected from homes and stores, only two products came back abnormal. The tests included free and total amino acid profiles.

Even if one assumes that the analysis reported by Mr. Schulof is more reliable or reputable, it still does not offer much information other than that there is a problem in formulation with grain-free and legume-focused diets. These are all diets marketed as complete & balanced. If they are deficient in essential amino acids, that is a big problem. If it is happening disproportionately in certain formulations, it is an indication that those ingredients may need special attention to ensure deficiencies don’t occur, as in lamb & rice diets.

It is also worth considering that reputable and responsible pet food manufacturers test their final physical products (not just the formulation) for nutritional adequacy. Furthermore, even when a nutrient is present, it is not always in a form with adequate bio-availability, underscoring the importance of long-term feeding trials and testing of animal blood values, not just analysis of the product.

Myth: Dogs have not been shown to improve with diet-change alone, because many receive taurine supplementation and heart medications.

First and foremost, dogs diagnosed with genetic forms of DCM do not show improvement, even with months of heart medications. That is because the medications function by supporting heart function, not healing damage to the heart. Some have called to question the documented improvements of dogs in the studies referenced above, as the dogs were receiving taurine supplementation in addition to a change in diet. While it is true that dogs have been documented to show improvements in DCM when receiving taurine, that is only when taurine-deficiency was the cause of the DCM development. In regards to the current FDA investigation, affected dogs have tested low, normal, and high for serum taurine. The dogs in Dr. Adin’s referenced study were not taurine-deficient, and therefore taurine alone would not be expected to create clinical improvement. The authors note the following: “ While it is difficult to draw conclusions from low case numbers, the single dog that did not receive taurine supplementation showed minimal echocardiographic improvement at 3 months but did improve 9 months after diagnosis, potentially suggesting slower improvement compared with dogs that were supplemented with taurine. Variability between dogs may also account for this slower improvement.”

Even beyond published literature, cardiologists across the US have reported to media and at conferences that they have seen clinical improvement among their patients even in absence of any medications or taurine alongside the change in diet.

Myth: This is a US-exclusive concern.

This trend was first recognized in the United States. That does not mean it is occurring exclusively in the US. Veterinary groups in other countries have released statements on monitoring the FDA investigation as it develops, and cases of diet-related DCM have been reported among international veterinary circles. Dr. Ryan Fries, a veterinary cardiologist and head of the cardiology department at University Illinois, has surveyed veterinary cardiologists internationally on DCM cases suspected to be nutritionally-mediated. He received responses from not just the US, but UK, Canada, Israel, and Austria. The results are not yet published, but were mentioned in the JAVMA article he co-authored.

If you’ve made it this far, surely you’re left to wonder — what DO we know?

Fact: Grain free diets, diets high in legumes or peas, and diets containing exotic ingredients are disproportionately associated with unexplained DCM across numerous breeds and we do not know why.

That the current cause is unknown is a call for caution, not complacency. In 2001, a similar piece to the one regarding DCM was published in JAVMA as a letter to the editor. It concerned preliminary evidence that raisins and grapes may be associated with acute renal failure in dogs. To date, it is still unknown what substance in grapes induces renal failure in some dogs. The toxic threshold is unpredictable, and many dogs have been observed to eat grapes their entire lives with no ill effects, while other dogs have gone into kidney failure and passed away after ingesting only a small number of them. Despite having only an association noted, even nearly two decades later, the ingestion of any amount of grapes or raisins is treated as a medical emergency. With no way of knowing whether a given dog will be hypersensitive and experience toxic effects, the risk is mitigated by avoiding grapes. The consequence of not providing treatment (emesis of the ingested grapes) to an animal that turns out to be sensitive to grapes is death. The consequences of not giving dogs grapes? Virtually non-existent.

Likewise, with no way of predicting what other factors are at play with the development of diet-associated DCM, the risk is mitigated by avoiding the known risk factors — grain-free formulations and formulations with significant legume / pea content. The consequence of not providing treatment (in this case, a change of diet) to an animal that develops nutritional DCM on is death. The consequences of avoiding grain-free diets and peas and legumes until more is known? Virtually non-existent.

Fact: To date, there is no evidence demonstrating that grain-free diets are necessary, or even beneficial, for dogs.

The literature simply is not there. The most oft cited reason for going grain free is mitigation of allergies. However, the most common allergies in dogs are seasonal and environmental. Of the small percentage that are dietary, chicken and beef are by far the most common culprits. For the very limited number of dogs with a true allergy to a grain, it is typically only to that one grain, not all types of grains. These dogs typically require hypoallergenic diets prepared in facilities designed to prevent undisclosed protein contamination.

Fact: There is no reason to suspect motivation within ‘Big Pet Food’ to demonize or otherwise scheme against raw, natural, grain-free, boutique, exotic, or any other niche formulation-type pet food manufacturers.

Nestle’s revenues are on the rise and they have attributed the growth to their petcare sector, Purina. They produce and sell both grain-free and natural lines.

Hills can say the same. While Royal Canin does not offer any OTC grain-free diets, they too have continued to experience company growth.

These companies are not threatened by the popularity of smaller manufacturers. If they were, they all have the funds and technology available to them to market niche formulations that appeal to changing trends in pet owner preferences and beliefs. They have more than enough financial ability to run extensive marketing campaigns to improve PR. Any scheme to paint grain-free formulas in a bad light would only backfire on themselves as well, as they carry grain-free lines. From a business perspective, they are more threatened by one another than other much smaller manufacturers.

These companies do frequently offer research grants and sponsor veterinary conferences. Every pet food company should do this — it shows that they are both principally and literally invested in the health and care of their primary consumers, your pets. Research is conducted to get answers that reflect reality, not provide results that cater to corporations. Some researchers do not even know where the funds for the research they’re conducting originated until after it is done. While it is always possible for malfeasance to occur, 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 (more reading here and here). Colgate offers grants for dental research. It is common for companies to invest in research relevant to their field, so that they can innovate and reflect the newest findings. Extra caution should be exercised when evaluating evidence from studies funded by sources that may sway results, but that does not mean the findings should be unanimously dismissed from the start. In this particular case, it is neither here nor there, as the FDA is a government agency conducting an investigation and receives no funding from corporate sponsors.

Purina, Hills, and Royal Canin have traditionally been recommended by veterinarians, and in many cases, continue to be. This has led some to suspect foul play and lined pockets, but the reality is that veterinarians receive extensive, non-sponsored education on nutrition as part of their curriculum. These brands are recommended by professionals because they conduct, publish, and fund extensive research in nutrition, have top notch quality control procedures, and formulate their diets under the directives of large teams of experts including veterinary nutritionists. Vets are not paid money to feed or offer or recommend any specific diets. But, say they were? Imagine for a moment that you were offered by a company to get paid to feed your pets their food. If you had any suspicion that the food was less than ideal for your pet, would you do it? If the answer is no, consider why you believe your veterinarian would do any different, even having devoted their life and education to animal healthcare.

Fact: Your veterinarian, not any other pet professional, is your best source for accurate information regarding canine nutrition, particularly as it pertains to your individual animal.

As stated above, contrary to common myth, most veterinarians have received extensive medical training in nutrition, alongside other core topics like cardiology, surgery, and anatomy. While specific curriculum varies by school, a good grasp of nutritional sciences is necessary for understanding many disease processes that are mediated by nutrient deficiencies or excess. Nutrition is considered the fifth vital sign for small mammals, alongside temperature, pulse, respiration, and pain assessment. Every vet is expected at graduation to be competent in nutrition assessment. For more complex issues, there are nutrition specialists, certified through the American College of Veterinary Nutritionists. Just as your regular vet is capable of providing basic surgical services to you, with boarded surgeons reserved for severe illness, injury, and congenital defects, your regular vet is fully qualified to offer basic nutrition information to you, such as what to feed, how much to feed, and how diet can impact health with boarded nutritionists ideal for consult in formulating a home diet or addressing unique dietary needs.

This issue is frustrating. It is daunting, scary, and it is confusing. The ease with which false or misleading information can be disseminated these days is alarming and the constant push to triple check everything is exhausting for even the most scholarly among us. Finding a trusted network of reputable resources is invaluable. Request sources, inquire about credentials, and do not allow anyone to demand you take information at face value or allegation alone. With time, the age of shouting “fake news!” and pointing fingers at opposing positions will pass, and intellectual clarity will be regained. Until that time, do your due diligence. We owe it to ourselves to stay well-informed, but more than ever, we owe it to our pets, who cannot do it for themselves.