DCM Study Review

Summary

“Board Invited Review: Review of canine dilated cardiomyopathy in the wake of diet-associated concerns,” 

AUTHORS: 

Sydney R. McCauley – Virginia Polytechnic Institute & State University – 

Published by Oxford University  Press on behalf of the American  Society of Animal Science, Journal  of Animal Science, June 2020 

Department of Animal & Poultry Sciences 

Stephanie D Clark, PhD, CVT, PAS – Clinical and applied nutrition,  Trained FSMA/AAFCO/ Regulatory/ HIPAA, IACUC, IRB, SHEA Guidelines Bradley W. Quest Renee Streeter, DVM, DACVN 

Eva M Oxford, DVM, PhD, DACVIM (cardiology)- Adjunct Assistant Professor,  Molecular Medicine at Cornell University 

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“Confounding variables and lack of controlling for independent variables can  

introduce bias and suggest a correlation when none exists.”

Incidence of heart disease

Despite no definitive correlation for grain-free diets  or their ingredients to DCM, some veterinary  cardiologists and researchers are recommending pet owners  switch their dogs to grain-based diets, without exotic protein  sources and avoiding boutique brands. Yet, others state  there is insufficient evidence-based research on  whether diet is the cause for the subjective claims.”  

Requirements for an effective review of data

Sampling bias* – “Regardless of what diet the dog is eating,  asking the veterinary community and the public for DCM cases  in dogs only eating grain-free or exotic protein diets will result  in sampling bias.”  

Diagnostics** - “Echocardiography is necessary to definitively  differentiate DCM from other cardiovascular diseases. It is  important to note that a normal ECG does not rule out the  presence of DCM, as most arrythmias are intermittent and have  high day-to-day variability.” 

“In 2018 a longitudinal study was noted for having one of the  largest sample size populations that assessed taurine  concentration in Golden Retrievers. … (implemented  treatments included) a diet change, administration of  supplemental taurine, with or without L-carnitine, inotropic  agents, diuretics, ACE inhibitors, and calcium channel blockers.  Despite inconsistencies, the study concluded that taurine  supplementation could slow down the progression of DCM in  dogs fed commercial diets. Since not all dogs received the  same treatment, determining which variables had any  

75% of cardiovascular disease in dogs is chronic  degenerative valve disease 

The 2nd most common cardiovascular disease in dogs is  DCM 

0.5%-1.3% of all dogs suffer from a form of  cardiovascular disease 

“A review of the current literature reveals gaps  within DCM studies in dogs, including: 

- Sampling bias,* 

- Inconsistencies in sampling parameters, - Confounding variables,  

- Lack of complete data for case studies in  DCM, and 

- Known genetic predisposition in certain dog  breeds.” 

Additional, generally unmet, scientific requirements  include: 

- Knowledge of the incidence 

- Clinical manifestations, complete medical  records (identify confounding variables) 

- Diagnostics** 

- Potential treatment required and  

standardization of treatments (diet,  

supplements, pharmaceuticals) provided 

- Knowledge of duration of previous diet - Use of a single laboratory for analyzing  blood parameters to prevent the use of  

different reference ranges 

- Analysis of one variable at a time 

correlations to these improvements can be challenging if not impossible.”  

Scientifically proven contributing factors to the development of DCM and Heart Disease: 

“Prevention of non-inherited cases of DCM is difficult in most cases, 

as arrhythmias, infectious disease, and hypothyroidism are not preventable.” 

Hypothyroidism and Endocrine Disease – “Thyroid hormones regulate key proteins involved in positive cardiac  ionotropy and chronotropy. Clinically hypothyroid dogs may have decreased systolic function, low QRS voltages, weak  apex beat, and sinus bradycardia due to poor hormone regulation. Thus, hypothyroidism can lead secondarily to DCM.” Large amounts of “spinach, cassava (tapioca), peanuts, soybeans, strawberries, sweet potatoes, peaches, pears,  broccoli, brussels sprouts, cabbage, canola, cauliflower, mustard greens, radishes and rapeseed have properties that  suppress the function of the thyroid gland, increasing the risk of hypothyroidism.” 

Myocarditis (Infectious/inflammatory insults) – “Myocarditis in humans and dogs is commonly viral in origin.  Myocarditis is reported in cases infected with Parvovirus, Borrelia burgdorferi (Lyme disease), Bartonella, Trypanosoma  cruzi, Neospora caninum. In many cases of suspected myocarditis, the source of infection is not identified.” 

Genetics - Dystrophin (DMD) in German Shorthair Pointer’s, Striatin (STRN) in Boxers, Pyruvate Dehydrogenase Kinase  4 (PDK4) and a locus on chromosome 5 in Dobermans 

Elevation of Cardiac Troponin-I (cTnI) as seen in Doberman Pinscher research.  

Chronic Tachycardia/ High Arrhythmic Load –“results in increased oxygen demand, decreased myocardial blood supply,  loss and eccentric hypertrophy of myocytes, abnormal calcium handling and reduced ATP production.” 

Results of laboratory analysis done by Know Your Pet Food, an initiative of Paws for Change, found the following Amino  Acid results in five (5) randomly selected consumer accessible dry kibble dog foods: 

Natural Balance (grain-free) – Lowest in Cysteine/Taurine, #2 in Methionine 

Purina Pro Plan (grains) – Highest in Cysteine and Methionine 

Royal Canin (grains) 2nd lowest in Cysteine, Moderate in Methionine 

Taste of the Wild (grain-free) – Mod. Cysteine, 2nd lowest in Methionine V-Dog (Vegan, grains) – 2nd highest in Cysteine, Lowest in Methionine 

Methionine & Cysteine Deficiency – “these Sulphur containing amino  acids are used to synthesize taurine. Deficiencies of these amino acids  may occur from poor bioavailability of ingredients, degradation during  high-heat processing (as is done with most kibble and canned pet  foods), or failure to add sufficient supplementation to a diet. One  study demonstrated that dogs eating diets containing such as animal  “meals” (rendered meats), turkey, whole grain rice, rice bran or barley  had low plasma methionine and cysteine concentrations.” 

Choline deficiency – “As a methyl donor, choline is important for the  regeneration of methionine from homocysteine. When choline stores  are deficient, the capacity to methylate homocysteine to methionine  is diminished resulting in increased plasma homocysteine  concentration. Elevated homocysteine concentrations are associated  with increased risk of cardiovascular diseases in humans.” 

Taurine deficiency – “While Taurine is not  currently considered an essential amino acid  in dogs, it is considered an essential amino in  cats. This is due to cats having a lower activity  of cysteine sulfinic acid decarboxylase  affecting the biosynthesis of taurine. Studies  evaluating if taurine should be considered an  essential amino acid in dogs have not been  conclusive. Studies have found that breeds  that are predisposed to DCM often have  normal taurine concentrations, indicating  that taurine was not contributing to the  development of DCM. Currently, studies  suggest that there may be breed-specific  taurine concentration reference ranges and  that one range cannot be applied across all  breeds. Certain breeds are more associated  with taurine-deficient DCM than others.” 

Carnitine deficiency – “Carnitine is … synthesized endogenously in the liver. Carnitine assists in the transport of long chain fatty acids from the cytosol to the mitochondrial matrix; once inside, it undergoes beta-oxidation to generate  energy. Roughly, 60% of the total energy production for the heart is through beta-oxidation. Carnitine also plays an  important role in the buffering of toxic levels of acyl CoA in the mitochondria to allow beta-oxidation to continue.  Therefore, deficiency in carnitine could cause cardiac dysfunction leading to cardiac diseases, including DCM. 

Results of laboratory analysis done by Know  Your Pet Food, an initiative of Paws for  Change, found the following mineral/heavy  metal results in five (5) randomly selected  consumer accessible dry kibble pet foods

(Products tested were as follows – Purina Pro Plan Chicken/Rice (contains grains), Royal Canin GI Low-Fat (RC) (contains grains), Taste of the Wild Pacific Stream (TOTW) (grain-free), Natural  Balance Sweet Potato/Fish (NB) (grain-free), V-Dog Vegan (contains grains)) 

Selenium All of the products tested contains  Sodium Selenite. None of the dry kibble products  tested contained detectible levels of Selenium.  

Copper deficiency – “Copper is necessary in the  production of hemoglobin, myelin, and melanin, as  well as maintaining the strength of blood vessels,  epithelial tissue and connective tissue. Thus,  deficiency in copper can have detrimental  implications for cardiac function. The effects of  copper deficiency range from anemia, CHF,  myocardial necrosis, calcification, and cardiac  hypertrophy. Research into relative copper  deficiencies which could be caused by excessive  dietary zinc or iron and the correlation with potential  copper deficiency and cardiac health in dogs.” 

Scientific literature notes that iron intake in excess of  60mg/kg can result in severe toxicity and lead to  severe morbidity and mortality in humans (AAFCO  indicates that no studies have been done in dogs).  

Therefore, toxic levels of iron were found in as little  as 1.8oz of Natural Balance (1/2 cup) to 9.4oz of  Purina (2 ¾ cups).  

Iron Toxicity – Ho-Wang Yuen; Wenxia Becker, 2020 

https://www.ncbi.nlm.nih.gov/books/NBK459224/ 

Vitamin E and Selenium deficiency – “Vitamin E works with the  selenium-containing enzyme, Glutathione Peroxidase, to  scavenge free radicals & prevent oxidative damage to  polyunsaturated fatty acids. Dogs with DCM have significantly  lower vitamin E concentrations and reduced glutathione  peroxidase, which is involved in cysteine synthesis when  compared to healthy dogs. Selenium is more available in its  organic forms, seleno-cysteine & seleno-methionine, rather than  the inorganic form, selenite. Selenium deficiency increases the  occurrence of myocarditis and cardiomyopathy in mice exposed  to both virulent and avirulant Coxsachie virus due to reduced  glutathione peroxidase. Thus, glutathione peroxidase may  protect against virally induced cardiac inflammation because  reactive oxygen species may enhance viral replication.” 

Copper – 

AAFCO requires a minimum of 7.3mg/kg of Copper Purina Pro Plan – 18mg/kg 

Royal Canin – 16.5mg/kg 

Taste of the Wild – 14mg/kg 

Natural Balance – 31.5mg/kg 

V-Dog – 24.5mg/kg 

No tested products were deficient in Copper. However… 

Zinc/Iron – 

AAFCO requires a minimum of 80mg/kg of Zinc 

AAFCO requires a minimum of 40mg/kg of Iron 

Purina Pro Plan – 

Zinc = 257mg/kg (3.2x min), Iron = 224mg/kg (5.6x min) Royal Canin – 

Zinc = 242mg/kg (3x min), Iron = 281mg/kg (7x min) Taste of the Wild – 

Zinc = 190mg/kg (2.4x min), Iron = 365mg/kg (9x min) Natural Balance – 

Zinc = 170mg/kg (2x min), Iron = 1,200mg/kg (30x min) 

Potassium deficiency – “decreased potassium intake can  induce a taurine depletion that can contribute to  cardiovascular diseases in cats. 50% of cats provided diets  sufficient in supplemental taurine, but deficient in potassium,  still developed DCM and thromboembolisms while those fed  sufficient potassium did not.” 

V-Dog – 

Zinc = 170mg/kg (2x min), Iron = 301mg/kg (7.5x min) 

Lead/Arsenic/Cadmium/Mercury – 

Lead – Purina/TOTW – 84.9ppb, Royal Canin – 284ppb,  Natural Balance – 303ppb, VDog – 140ppb Arsenic – Purina/Royal Canin/ Natural Balance – 176ppb, TOTW – 147ppb, VDog – 

Heavy Metals – “Since Taurine detoxifies heavy metals, there is an increase in  the demand, which may result in a taurine deficiency. More specifically,  taurine depletion can occur during arsenic-induced cardiomyocyte viability,  reactive oxygen species products, intracellular calcium, and apoptotic cell  death. Taurine has also been observed to reduce cadmium-indices damages in  murine hearts and hypothalamus. A similar effect is exhibited in rats with  taurine and its hepatoprotective effects against mercury toxicosis.”

160ppb 

Cadmium – Purina – 58ppb, Royal  Canin – 84.7ppb, TOTW/Natural  Balance – 52.9ppb, VDog – 66.2ppb Mercury – Purina and VDog – Not  Detected, RC/TOTW/ NB – Detected  under 10.7ppb 

Results of laboratory analysis done by Know Your  Pet Food, an initiative of Paws for Change, found  the following results in five (5) randomly selected  consumer accessible dry kibble pet foods 

(Products tested were as follows – Purina Pro Plan Chicken/Rice (contains  grains), Royal Canin GI Low-Fat (RC) (contains grains), Taste of the Wild  Pacific Stream (TOTW) (grain-free), Natural Balance Sweet Potato/Fish (NB) (grain-free), V-Dog Vegan (contains grains)) 

Purina Pro Plan – (grain containing diet) 

Carbohydrate – 45% 

Fiber/Ash – 5.94% (stated maximum = 3%) Protein (includes vegetable/filler protein) – 32.22% (max 0.7oz “meat” per cup) 

Fat – 11.01% (stated minimum = 14%) 

Phytic Acid (antinutrient) – 5566mg/100g (5.6%) 

Royal Canin GI Low Fat (grain containing diet) Carbohydrate – 59% 

Fiber/Ash – 6.39% (stated maximum = 3.6%) Protein (includes vegetable/filler protein) – 21.59% (max 0.4oz “meat” per cup) 

Fat – 4.21% (stated minimum = 4.5%) 

Phytic Acid – 3837mg/100g (3.8%) 

Taste of the Wild Pacific Stream – (grain free diet) Carbohydrate – 47% 

Fiber/Ash – 7.02% 

Protein (includes vegetable/filler protein) – 27.08% (max 0.6oz “meat” per cup) 

Fat – 12.01% (stated minimum = 15%) 

Phytic Acid – 5014mg/100g (5%) 

Natural Balance Sweet Potato& Fish – (grain free diet) Carbohydrate – 54% 

Fiber/Ash – 9.73% (stated maximum = 4.5%) Protein (to include all vegetable/filler protein) – 20.7% (stated minimum = 21%) 

(max 0.4oz “meat” per cup) 

Fat – 7.48% (stated minimum = 10%) 

Phytic Acid – 6289mg/100g (6.3%) 

VDog Vegan – (grain containing diet) 

Carbohydrate – 53% 

Fiber/Ash – 7.8% (stated maximum = 5%) 

Protein (to include all vegetable/filler protein) – 25.35% 

(while this product should contain 0% meat, beef  protein was detected in one lab analysis, likely due to  cross-contamination) 

Fat – 6.25% (stated minimum = 9%) 

Phytic Acid – 5898mg/100g (5.9%) 

Excessive Levels of Insoluble Fibers – “The GI tract has been  identified as the primary location where sulfur-containing amino  acids are metabolized… it has been demonstrated that certain  dietary fiber, such as non-starch polysaccharides, are relatively  nonfermentable and have anti-nutritive effects. This can lead to  a decreases in sulfur-containing amino acids and result in  nutrient deficiencies, such as taurine or carnitine.” 

“(One) study hypothesized that diets, which were formulated to  meet AAFCO requirements, may not actually be meeting the  dogs’ nutritional needs due to fiber’s negative effect on  nutrient absorption. Fiber can also influence fermentation by products from microbes in the hindgut and hinder reabsorption  of taurine, even if taurine is biosynthesized in sufficient  amounts. For example, fiber in the form of unrefined cereals,  legumes, nuts, oilseeds, fruits and vegetables can reduce the  absorption of fats and fat-soluble vitamins” 

Tofu-based Diets – “While (tofu is) lower in protein, AAFCO  requirements for protein were met. Tofu is made from soybean cure, which is low in sulfur-containing amino acids, devoid of  taurine and may have contributed to the cause.” 

Low-Protein Diets Designed for the Management of Urate  Stones – “this may be due to low protein diets being low in  essential and nonessential amino acids or vital precursors for  carnitine and taurine synthesis.” 

Cassava (tapioca) and cyanide – “Cassava is known to  accumulate cyanogenic glycosides, cyanide. When cyanide is  consumed, it is converted into thiocyanate, which requires  sulfane sulfur from sulfur-containing amino acids during  detoxification. There is an increased demand for sulfur containing amino acids during detoxification. This can limit the  availability of sulfur-containing amino acids used to  biosynthesize taurine and carnitine.” 

Popular brands that use Tapioca (Cassava) – Nature’s Variety  Instinct, Merrick, Eden, Petcurean Go!, Nutri Source, Earthborn  Holistic & Zoic 

https://petfoodreviewer.com/tapioca-in-dog-food/ 

Phytic Acid can bind to necessary minerals and block enzymes,  leading to digestive trouble or mineral deficiencies. Mineral  deficiencies can result in pain syndromes similar to fibromyalgia.  Despite some potential antioxidant properties, it is  recommended that intake is limited to 100-400mg per day. 

Of the 5 kibble products tested by Know Your Pet Food, Phytic  Acid levels averaged 5,321mg per cup of food

https://www.integrativepainscienceinstitute.com/ - Phytic Acid – Top Reasons to Avoid this Anti-Nutrient 

Where FDA publications have failed the public and vets

“The use of the acronym “BEG” (Boutique, Exotic, Grain-Free) and its association with DCM are  without merit because there is no definitive evidence in the literature…it is impossible to  draw any definitive conclusions… linking specific diets or specific ingredients to DCM.”  

“Descriptors of pet foods implicated to have a subjective association with DCM are diets  with specific characteristics, such as, but not limited to, containing legumes, grain-free novel  protein sources and ingredients, and smaller manufactured brands. However, an exhaustive  review of the literature provides evidence of conflicting information. For example, boutique  diets, defined as produced by a small manufacturer, have been implicated in association  with DCM. However, when the FDA report is broken down into which pet food  manufacturers made the called-out diets, 49% of the brands listed were made by one of the  six largest pet food manufactures in North America. Given that almost half of the brands  listed on the FDA report on June 27, 2019, are not manufactured by boutique pet food  companies it is unlikely that an association can be made to DCM.” 

Breeds prone to DCM  regardless of diet: 

DCM in dogs is more  prevalent in males than  in females 

DCM is also a disease of  middle aged to older  dogs 

Doberman Pinschers Irish Wolfhounds 

Great Danes 

“The FDA … lists the top seven proteins of the  implicated diets: chicken, lamb, salmon,  whitefish, turkey, beef and pork. These  comprised 75% of the diets named in the FDA  report which are not exotic pet food  proteins… suggesting exotic protein sources  may not lead to the development of DCM.” 

“(One) study concluded that whole blood  taurine concentrations were lower in dogs  fed whole grain diets, such as rice bran  and barley, while another study observed  that beet pulp, rather than rice, had a  greater impact on lowering the  concentrations of plasma and whole  blood taurine. This suggests that these  

Boxers 

American Cocker  Spaniels 

Bulldogs 

Golden Retrievers 

ingredients are likely not a cause of the taurine-deficiency in dogs. However, the FDA has  currently raised concern for diets that contain legumes as one of the top seven ingredients.  According to the FDA’s 2018 report, lentils, peas, and other legumes (pulse ingredients)  have been speculated to be responsible for diet-associated DCM. However, this hypothesis  may be unsupported by evidence-based research. In a study conducted at the University of  Illinois, in a controlled environment, dogs were fed 45% legumes or fed a diet primarily  comprised of poultry byproduct. Interestingly, over the 90-d study, there was no significant  difference when comparing plasma amino acids between groups. Additionally, comparing  the plasma and whole blood taurine concentrations between groups was not significantly different. Therefore, since there was no change in taurine concentrations with dogs being  fed a diet containing 45% legumes, legumes are more than likely not a cause of taurine deficient DCM.”  

Saint Bernards 

Airedale Terriers 

Newfoundlands 

Scottish Deerhounds English Cocker Spaniels 

German Shorthair  Pointers 

A 2020 publication on DCM “was not well-controlled from a nutritional standpoint. The study  evaluated two groups: traditional diets and non-traditional diets; however, the non-traditional diet  group was comprised balanced AND those used only for supplemental feeding, which are not  formulated to meet AAFCO requirements. Furthermore, the majority of the dogs eating he non traditional diets did not have low taurine or abnormal cardiac parameters. Moreover, not all dogs with  decreased systolic function had low taurine concentrations, and the relationship between whole blood  taurine, plasma taurine, and cardiac muscle taurine concentration remains unknown.”

“In recent FDA reports, of the 340 dogs’ medical records reviewed, 202 (only 36%) had a definitive diagnosis of DCM,  confirmed by an echocardiogram. The FDA Vet-LIRN states that 176 (only 31%) of the dogs diagnosed with cardiovascular  disease had taurine measurements and echocardiograms. However, the report does not provide details on whether it has  been suggested that whole blood taurine may be more indicative of the actual taurine status of the dog than plasma  taurine.” Further, “the FDA reports do not have complete medical records and diet histories for all dogs… of the 515 dogs, 

14 dogs(only 2.7%) have provided initial samples for the 1 to 2-mo follow-up. 44% of DCM diagnosed dogs had concurrent  conditions which can lead to the development of cardiovascular diseases. 15% of the dogs had valvular degeneration, 12%  had atrial fibrillation, 9% had hypothyroidism and 8% had Lyme disease. 61% of dogs with chronic valvular disease or DCM  have another concurrent condition… therefore, dogs with these conditions… should not be included. The information  cannot be properly analyzed if a case report does not contain all required information, therefore, it should not be included  in studies.” 

“In the FDA report, 13 (4%) of the dogs were reported  “unknown breed”, 62 (20%) mixed breeds, and the  remaining were named by breed. Of the 305 dogs that had  breeds listed 223 (73%) were identified as a breed  predisposed to DCM.…(leaving only 3% of dogs that could  effectively be analyzed for “new” or “abnormal” DCM cases) overrepresentation and breed reporting bias possibly  inflated the number of reported cases. An increase in  

A study done on 64 dogs with DCM showed that only 24 (37.5%) had blood samples submitted, only 14 (22%) of  those had low taurine and 6 were DCM prone breeds.  100% of the taurine deficient dogs were consuming  lamb & rice diets, 8 (67%) of which were consuming the  exact same product. Yet, all boutique brand products  are villainized as potential causes of DCM.  

reports due to awareness or concern regarding diet history and veterinarians knowledge of predisposed breeds resulted  in reporting bias and overrepresentation. To further understand incidence rate and if there is a possible increase in DCM,  multi-clinic, retrospective studies are warranted to identify a percentage of the population seeking referral to diagnose  DCM, the incidence in specific breeds, and diet history, comparison to market share.”  

Limiting factors in research:  

“Difficulty of antemortem testing of the  myocardium and out of pocket cost to screen for  nutritional deficiencies and infectious agents.” 

“Most definitive diagnoses in dogs are obtained  through postmortem histopathology. Due to  limitations in definitive testing modalities in  dogs, myocarditis is suspected to be  underrepresented as a cause of DCM.”

To read the full report, see

Required tests to effectively diagnose cardiac disease

- 25-h Holter monitoring 

- Comprehensive thyroid panel (T3, T4, TSH, TPO) - cTnI concentration 

- Infectious disease testing 

- L-Carnitine (free, total and carnitine ester concentrations)  - Plasma and Whole Blood Taurine 

- hs-CRP 

- Homocysteine  

- Mineral/Heavy Metal Analysis (HTMA Test ParsleyPet.com) 

Board Invited Review: Review of canine dilated cardiomyopathy in the wake of diet-associated concerns, Published by Oxford University Press on behalf of the American Society of Animal Science, Journal of Animal Science, June 2020 

AUTHORS: 

Sydney R. McCauley – Virginia Polytechnic Institute & State University – Department of Animal & Poultry Sciences Stephanie D Clark, PhD, CVT, PAS – Clinical and applied nutrition, Trained FSMA/AAFCO/ Regulatory/ HIPAA, IACUC, IRB, SHEA  Guidelines 

Bradley W. Quest  

Renee Streeter, DVM, DACVN 

Eva M Oxford, DVM, PhD, DACVIM (cardiology)- Adjunct Assistant Professor, Molecular Medicine at Cornell University