Development of plasma and whole blood taurine reference ranges and identification of dietary features associated with taurine deficiency and dilated cardiomyopathy in golden retrievers: A prospective, observational study
Authors: Bradley D Whelchel
Joshua Yu
Joshua A Stern
Andrea J Fascetti
Amanda E Crofton
Samantha L Fousse
Joanna L Kaplan
Ashley N Sharpe
Eric S Ontiveros
Journal: PLoS ONE (2020)
Discipline: Multidisciplinary
Keywords: FDA; consumer complaints; legume-rich; grain-free diets; dilated cardiomyopathy
Affiliations: Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California Davis, Davis, CA, United States of America., Department of Molecular Biosciences, School of Veterinary Medicine, University of California Davis, Davis, CA, United States of America.

Abstract:  Introduction: A surge in Food and Drug Administration (FDA) consumer complaints identified concerns that legume-rich, grain-free diets were associated with nutritionally-mediated dilated cardiomyopathy (DCM). Golden retrievers represent the most reported breed affected by this condition and previous studies documented the disease is responsive to dietary change and taurine supplementation. Although dietary findings across cases are compelling, prospective studies with control groups are lacking. The role of diet in developing taurine deficiency and echocardiographic changes consistent with DCM in healthy dogs is unknown. Objectives: We hypothesized that golden retrievers eating non-traditional diets are at a higher risk of having taurine deficiency and nutritionally-mediated DCM compared with those eating traditional commercial diets. We aimed to compare taurine concentrations and echocardiographic indices of systolic function between golden retrievers in each diet group and elucidate associations between diet and these variables. Additionally, we aimed to generate breed-specific reference intervals for whole blood and plasma taurine concentrations. Animals: 86 golden retrievers. Methods: Golden retrievers eating traditional or non-traditional diets were evaluated and diet history, taurine concentrations and echocardiographic data were collected. Dietary features, taurine concentrations and echocardiographic findings were compared between diet groups. Relative risks were calculated for the likelihood of echocardiographic abnormalities and taurine deficiency in each diet group. Breed-specific reference intervals were constructed for taurine concentrations in dogs from the traditional diet group. Results: Golden retrievers eating non-traditional diets had significantly lower taurine concentrations and more frequent systolic dysfunction. Breed specific reference intervals are higher than previously reported across breeds. Conclusions: Non-traditional diets, which were typically grain-free and contained legumes in this study, were significantly associated with and have increased relative risk for the identification of taurine deficiency and echocardiographic abnormalities consistent with nutritionally-mediated DCM. These findings were identifiable in the absence of clinical signs and support the findings of multiple previous studies and the ongoing FDA investigation. 

Retracted: No

PubPeer comments:
 2020 expression of concern. https: journals.plos.org plosone article?id=10.1371 journal.pone.0239078 After this article [1] was published, concerns were raised about undeclared competing interests, and about the study design and conclusions. In response to the concerns about declaration of potential competing interests, the authors have provided the following update to the Competing Interests statement: AJF is the Scientific Director and JY is the Technical Director of the Amino Acid Laboratory at the University of California, Davis (UCD) that provides amino acid analysis on a fee for service basis. AJF received remuneration for lectures or as an advisor on behalf of Nestlu00e9 Purina PetCare, Mars Petcare, Synergy Food Ingredients, the Mark Morris and Pet Food Institutes. AJF received funding from Nutro for graduate student training. A resident on the Nutrition Service, mentored in part by AJF, received funds from the Hillu2019s Pet Nutrition Resident Clinical Study Grants program, matched by the Center for Companion Animal Health, School of Veterinary Medicine at UCD. The Veterinary Medical Teaching Hospital at UCD received funding from Royal Canin to support a resident, and from Nestlu00e9 Purina PetCare to partially support a nutrition technician. AJF has a contract with the FDA on unrelated research. Since the time of article submission, JAS has received research support from Natureu2019s Variety Inc. Collectively, this did not influence the collection or interpretation of results in this study. There are no patents, products in development or marketed products to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials. Concerns raised about the study are outlined below. The authors noted that some of these issues were discussed during pre-publication peer review and or in the published article. 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. 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. 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. Questions were raised about the statistical analyses reported in the article. 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. 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 subjectu2019s current diet may impact the study outcomes. Concerns were also raised about differences between groups in the average time on the current diet. Questions were raised about the validity of the conclusion statement, u201cGrain 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.u201d The article [1] 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 articleu2019s conclusions. Meanwhile, the PLOS ONE Editors issue this Expression of Concern. Reference 1.Ontiveros ES, Whelchel BD, Yu J, Kaplan JL, Sharpe AN, Fousse SL, et al. (2020) Development of plasma and whole blood taurine reference ranges and identification of dietary features associated with taurine deficiency and dilated cardiomyopathy in golden retrievers: A prospective, observational study. PLoS ONE 15(5): e0233206. https: doi.org 10.1371 journal.pone.0233206 ,