A press release touting a new paper on what's known about diet and a heart condition called dilated cardiomyopathy emphasized the doubt: "Peer-reviewed article finds existing research does not support speculated link between grain-free diets and dilated cardiomyopathy (DCM) in dogs," the title reads, followed by the subheading, "Journal of Animal Science publishes analysis of more than 150 studies."
The news was, at first glance, a bombshell in the veterinary and dog-owning worlds. Then it backfired.
Within two days of the paper's June 15 online posting, veterinarians responded with indignation. Among their criticisms: The paper was not an analysis but a recitation of earlier work done by others. Few of the 150-or-so studies reviewed were directly relevant to the question of whether certain diets were causing DCM in dogs, an association recognized only two years ago. The authors cherry-picked past research, emphasizing data that suggests a link between diet and DCM is flawed, and ignoring evidence that corroborates it — particularly, evidence that changing the dog's diet has reversed the disease.
Most troubling of all, critics said, the authors failed to disclose that their employer, BSM Partners — an animal-food consulting company that funded the study — works with a pet food brand implicated in a U.S. Food and Drug Administration investigation into possible diet-related causes of DCM in dogs.
In short, the paper quickly was clouded by suspicions of a conflict of interest that the researchers did not acknowledge. The paper states: "The authors declare no real or perceived conflicts of interest."
A lively discussion of the issue that started privately among veterinarians on the Veterinary Information Network, an online community for the profession and parent of the VIN News Service, spread to the public domain through the Facebook page of a publication called The Canine Review.
One Facebook user wrote: "It’s expected that dog food companies will fund research in the field, if they don’t who will? But conflict should be disclosed."
The social media discussion drew Meghan Wulster-Radcliffe, CEO of the American Society of Animal Science, which publishes the Journal of Animal Science. Responding to the criticism, she wrote: "[A]uthors did not list a conflict of interest as they were not reporting primary data from a study they funded but rather a review of literature and they are very clear about their work affiliations in the article."
But following inquiries from the media and members of the veterinary community, the ASAS issued a statement on June 25 — 10 days after the paper came out — that it would publish a corrigendum, or correction, to explicitly describe the study authors' relationship with the pet food industry.
Those unhappy about the original publication said it was too late.
"No matter what, even if they retracted the article, it's already out there," said Dr. Steve Valeika, an academic-turned-general practitioner in North Carolina, with a doctorate in epidemiology. "The press releases are out there, the pet food industry knows, and the pet owners at whatever store they buy their food from, they've heard it from the salespeople: 'They've analyzed 150 studies!'
"When I saw the title [of the press release], I thought it was a meta-analysis," Valeika added, referring to a statistical method of synthesizing the results of different studies. "It's not an analysis. It's a book report on DCM."
Diet associated with deaths of more than 100 dogs
In DCM, the heart muscle becomes weak and cannot pump blood efficiently. Dogs with the disease may tire quickly, cough or struggle to breathe. They may become abruptly weak, collapse, faint or die suddenly. In certain breeds, including Doberman pinschers, Great Danes, Irish wolfhounds and cocker spaniels, the condition is inherited. About two years ago, veterinary cardiologists began noticing the condition in dog breeds that had rarely, if ever, developed DCM before.
The cases led clinicians and researchers to consider the role of food. Initially, the suspected culprit was grain-free diets, which have become ubiquitous in the past decade. Further investigation led researchers to focus on formulations containing as main ingredients peas, lentils or other legumes; seeds of legumes (called pulses); or potatoes. Some of the implicated formulations are labeled "grain-free" but not all of them, the FDA reported last year.
In its most recent update on the issue, in June 2019, the FDA said it had received reports of 560 dogs and 14 cats diagnosed with DCM from 2014 through April 30, 2019. Of those, 119 dogs and five cats had died. The tally did not include "the many" reports of pets with non-DCM cardiac issues, which the agency said could indicate heart changes that precede DCM.
Asked for comment about the new review paper, the agency provided this statement: "The FDA does not typically comment on specific studies or papers, but evaluates them as part of the body of evidence to further our understanding about a particular issue and assist in our mission to protect public health. We are continuing to investigate cases of DCM reported to the agency and continue to work with the veterinary and scientific community on this issue. We will communicate publicly when there are significant developments to report."
BSM-Zignature link raises eyebrows
The company that funded the recently published review paper and employs its authors is BSM Partners. The company was established in 2011 and is based in Bentonville, Arkansas. Dr. Renee Streeter, a boarded veterinary nutritionist who serves as principal nutritionist at BSM and is a co-author on the paper, describes BSM as a "full-service consulting firm for the industry. We help make hundreds of products a year [for clients that] range from very large companies to very small companies, producing all types of pet food products and supplements and treats," she said.
The BSM client that's raised eyebrows among skeptical readers of the paper is Pets Global, owner of the Zignature brand of dog food. Zignature landed on a list released by the FDA last year of the 16 brands named most frequently in reports of canine DCM received by the agency since 2014. Zignature appeared 64 times, second only to Acana, at 67.
Pets Global touts its association with BSM Partners on the Zignature website: "They work with us to formulate our complete and balanced recipes ..."
Owing to the popularity of grain-free and other unconventional formulations, often carried in high-end pet stores, the issue is a hot button. In a telephone interview with VIN News, Streeter said she and her colleagues anticipated early on that the paper would be provocative. "Maybe not to the degree [it has been], but yes," she said. "We knew that this is a highly debated topic and we really wanted to take those first steps by identifying the gaps in the knowledge and using that as a starting place to guide future research.
"I knew that people would have feelings about it, of course," she continued. "You can't be in veterinary medicine and be in industry and not realize what a big deal this is. We need to take it seriously. And pretty much, people are, which is awesome."
All of the paper authors are employees of BSM, Streeter said. Sydney McCauley, the lead author, has a doctorate in nutrition. Stephanie Clark is a veterinary technologist with a doctorate in nutrition. Dr. Eva Oxford is a boarded veterinary cardiologist in private practice and heads the BSM research department, Streeter said. Dr. Bradley Quest is the firm's principal veterinarian. Zignature's website describes Quest as "our veterinarian on staff" but Streeter said Quest is not on staff at Zignature and never has been. Rather, he provides consulting services to Zignature, as to other BSM clients, she said.
Because the authors disclosed in the paper that the work was funded by BSM, Streeter said, they did not believe further elaboration was necessary. "Certainly we are not industry," she said. "We work with so many different people that we certainly don't see ourselves as biased, because what we do for one person will be different for another person, based on their needs. ... We have [as a client] one company that has been implicated [in the association between diets and DCM], and all the rest have not been."
Asked for the identities of BSM clients other than Zignature, she said non-disclosure agreements prohibit her from naming them.
Inquiries about the paper authors' perceived bias prompted an internal review at ASAS, the journal publisher, of its conflict-of-interest policy. The organization concluded that the case "does not constitute a COI [conflict of interest] failure ..." it said in its June 25 statement.
However, the statement continues, "We understand that readership could nonetheless have transparency concerns. Consequently, ASAS will publish a corrigendum in Journal of Animal Science that states, 'In response to reader inquiries, we are adding the following statement for clarity: BSM Partners provides nutritional advice for pet food companies of all sizes, including both those that produce grain-free, pulse-rich pet foods, and those that produce grain-inclusive, pulse-free pet foods.' ”
ASAS staff told VIN News today that the corrigendum will be posted by Friday.
The response strikes Valeika, the veterinary clinician and epidemiologist, as inadequate. He points to a 2018 article in the Journal of Veterinary Internal Medicine as an example of a conflict-of-interest statement done right. The article evaluates three diagnostic tests, one of them produced by the animal health company Zoetis. A conflict-of-interest declaration reads: "This work was funded by Zoetis, Inc. All the authors are employed by Zoetis, and WITNESS Lepto is a product of the company with a business and/or financial interest."
Valeika said it is entirely appropriate for scientists at BSM or any pet food company to contribute to the discussion and the science on the possible role of diet in DCM. They just need to be transparent about who they are, he said. "If a conflict of interest meant you couldn't publish, you couldn't publish anything," Valeika said. "Anyone who's ever taken an honorarium for speaking at a meeting couldn't publish."
How the review paper developed
The canine DCM paper is labeled as a "board invited review." Asked to elaborate, ASAS CEO Wulster-Radcliffe replied by email: "Multiple times per year, we solicit topics and potential authors from the membership. After soliciting from the membership, the EiC [editor in chief] can invite a review. The board sees and approves the topics. The potential authors are submitted by the membership. The EiC chooses which topics and authors. Occasionally, the board will have a topic they ask the membership for authors. This one came from a member solicitation by the EiC."
Streeter said the team at BSM concurrently was interested in exploring the subject. "It came about initially that we were interested in doing it because we felt like it was such a big deal to the veterinary community and the scientific community at large," she said. "... We were working on it and investigating what journals would be interested. We spoke to JAS and they were very interested and invited us to submit."
Wulster-Radcliffe said the manuscript was peer-reviewed by three scientists from academia: two animal nutritionists and one companion-animal veterinary cardiologist. Submissions typically have two to four reviewers, she said.
Like Streeter, Wulster-Radcliffe said the ASAS and journal staff expected that the paper "would likely be controversial" because "the topic is inherently controversial." The peer reviewers "stated that we should anticipate some feedback, but [they] all felt it was a valid interpretation of the materials presented in the review," she said.
She added, "As always, if readers feel it is not a valid interpretation of available peer-reviewed data and or that the authors left key data out of the review, they are encouraged to write a letter to the editor."
Several participants in the VIN discussion are considering doing so. One is Dr. Mark Kittleson, a veterinary cardiologist who was involved in the 1980s in a groundbreaking discovery that DCM in cats can be reversed in most cases by supplementing their diets with taurine, an amino acid. (The lead author on the 1987 study about the finding is Dr. Paul Pion, president and co-founder of VIN. Pion also started the discussion on VIN questioning the integrity of the new canine DCM paper.)
In an interview, Kittleson said that the paper omits two critical points: "With these diets, we are now seeing DCM in breeds where we never saw it before," he said, "and in some percentage of dogs, the disease completely or partially reverses with diet change, and usually also with taurine supplementation."
He noted that the taurine supplementation is unlikely to be the reason the dogs recover because most of the patients given the supplement are not actually taurine-deficient. (Obtaining taurine through diet is essential for cats because they cannot synthesize the amino acid in their bodies, whereas dogs can, from other amino acids.)
Another critic of the paper is Caitlin Holly, a third-year veterinary student, who pushed back on the paper's conclusions in a June 19 post on her blog, Doc of All Trades.
"In reality, the publication in question is not truly a study, and it certainly doesn’t qualify as a meta-analysis," she wrote. "This is a non-systematic literature review, meaning the authors did not discuss their methodology for acquiring relevant literature, nor did they compare or combine analyses from the different studies on the subject."
Holly said fewer than 10 of the 150-plus citations in the paper directly address the question of DCM and its potential relation to grain-free, legume-rich and/or non-traditional protein diets.
"While existing research has not demonstrated a definitive causal relationship, it has suggested a definitive correlation," Holly wrote. "To say there is 'no link' is simply disingenuous."
In an interview, Holly said she was compelled to blog about the paper after viewing social media posts citing it as vindicating grain-free and related diets. "I started seeing influencers online talking about how, 'Oh, a year ago the FDA was causing all this panic, and now look,' " she said. "That started making me really angry, because I've talked to people online whose dogs are affected. ... I thought, something needs to be out there explaining. ... If you don't have a scientific background or a background in medicine, you might not understand why it's not what it looks like on the surface."
Further research ahead
On one aspect, all parties concur: More research is needed. "We're in full agreement with the fact that this is serious and that we need more information," Streeter, the paper co-author, said.
She said BSM is considering undertaking feeding trials in laboratory dogs, which would enable researchers to carefully control the animals' diets and other variables.
Told by VIN News about BSM's intentions, Valeika responded enthusiastically. "Great! I'm all for them doing that," he said, "as long as they're upfront and transparent."
He suggested that the researchers register their trial in advance, as a way to ensure openness. Trial registries were developed to discourage researchers from failing to publish results that don't comport with their interests.
Asked whether BSM scientists plan to register their trial, Streeter replied by email: "Prior to the studies, we submitted the research proposals to the FDA-CVM [Center for Veterinary Medicine] and have been following their suggestions to date."
The Pet Food Institute, a trade group said to represent 98% of U.S. pet food makers, offered a statement that carefully avoids taking sides. The statement, dated June 25 and signed by Dana Brooks, the group's president and CEO, reads in part:
"The U.S. Food & Drug Administration (FDA) has stated and PFI agrees that this is a complex issue with many components requiring scientific evaluation. Tens of millions of dogs enjoy grain-free diets in the United States and the number of submitted DCM reports suggest that, if diet is a factor, it may be among several elements involved, including dog physiology and genetics. PFI welcomes the continued dialogue among our pet food maker members, veterinarians, and ingredient suppliers to advance the understanding of DCM and its causes."
VIN News Service commentaries are opinion pieces presenting insights, personal experiences and/or perspectives on topical issues by members of the veterinary community. To submit a commentary for consideration, email firstname.lastname@example.org.