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Short Communication *Corresponding author Lisa Freeman, Cummings School of Veterinary Medicine, A pilot study investigating Tufts University, 200 Westboro Road, North Grafton, USA, Submitted: 30 October 2015 dietary factors with possible Accepted: 10 December 2015 Published: 12 December 2015 ISSN: 2378-931X associations with canine Copyright © 2015 Freeman et al. degenerative mitral valve OPEN ACCESS
Keywords disease • Nutrition • Cardiac disease 1 2 3 Jordan L Sauer , Lisa M. Freeman * and John E. Rush • Amino acids Department of Clinical Sciences, Cummings School of Veterinary Medicine, USA • Serotonin
Abstract The objective of this study was to measure dietary amino acids, choline, carnitine, serotonin, and ergovaline as possible dietary factors that could play a role in the pathophysiology of degenerative mitral valve disease (DMVD). Thirteen commercially available diets were selected for analysis, and were analyzed for macronutrients; amino acids; ergovaline; the indoleamines serotonin (5HT) and melatonin; as well as choline and free L-carnitine (n=12). There was a wide range in the concentrations of all analytes in the diets tested. No essential amino acids were below AAFCO Dog Food Nutrient Profile minimums.One diet was below the AAFCO Dog Food Nutrient Profile minimum for fat. Taurine, although not an essential amino acid for dogs, was below the AAFCO Cat Food Nutrient Profile minimum for taurine in 9 of 13 diets. Tryptophan ranged from 0.19-0.59% dry matter (median=0.28% dry matter). All 13 diets had undetectable ergovaline concentrations. One sample tested positive for 5HT, and melatonin was detected in 8 diets. There also was wide variation (3-fold and >100-fold difference, respectively) in choline and free L-carnitine concentrations among diets. Additional research is needed on the effects of varying dietary intake of tryptophan and other amino acids, 5HT, choline, and carnitine on cardiac valve metabolism. ABBREVIATIONS 5HT: serotonin; AAFCO: Association of American Feed synthesis [3,4]. Recently, studies have provided evidence that 5HT may play a role in the pathophysiology of DMVD [3,4,6,7]. There are multiple 5HT receptor types present in the canine and Control Officials; DMVD: Degenerative Mitral Valve Disease; NRC: human mitral valve [3]. Activation of 5HT-R2B receptors appears NationalINTRODUCTION Research Council; TMAO: Trimethylamine-N-oxide to play a role in valvulopathies in rodent models and people [8,9]. Elevated production of 5HT and resulting mitral valve lesions can be the result of disease (e.g., carcinoid tumors) or a variety of Degenerative mitral valve disease (DMVD) is the most serotoninergic and dopaminergic drugs [8,9]. Canine mitral valves common heart disease in dogs, affecting approximately 11% of also appear to be able to produce small amounts of 5HT under all dogs [1,2]. The histological changes associated with DMVD conditions of strain [4,10,11]. Dogs with naturally-occurring include deposition of proteoglycan and extracellular matrix, as DMVD have higher serum 5HT concentrations compared with well as disorganization and disruption of collagen and, while the controls and also have up-regulated 5HT-R2B transcription pathological changes have been well documented [3,4], the patho [6,12]. However, the cause for elevated 5HT concentrations is physiologic causes of DMVD remain unclear. One possible factor unknown and could be related to increased production, altered that may play a role in DMVD is serotonin (5-hydroxytryptamine metabolism, or decreased clearance. Increased dietary intake [5HT]).Serotonin is a neurotransmitter that plays an important of 5HT or its precursor tryptophan, for example, can increase role in mood, platelet function, sleep regulation, regulation of plasma 5HT concentrations [13]. It is unclear whether common food intake, and intestinal motility [5]. The majority of 5HT is dog foods contain any 5HT or its metabolite, melatonin, and if so, synthesized from tryptophan by enterochromaffin cells of the how much tryptophan concentrations vary among commercial intestines, although heart valves have the capacity for some 5HT dog foods. Cite this article: Sauer JL, Freeman LM, Rush JE (2015) A pilot study investigating dietary factors with possible associations with canine degenerative mitral valve disease. J Vet Med Res 2(5): 1035. Freeman et al. (2015) Email:
Central Bringing Excellence in Open Access MATERIALS & METHODS Dietary sources of ergot also could contribute to the development of DMVD [14]. Ergot is most commonly known For this pilot study, 13 diets were selected to investigate the in veterinary medicine for its role in fescue toxicosis, in which variability in dietary concentrations of amino acids, serotonin, certain grasses become infected with endophytes which ergovaline, choline, and L-carnitine.These diets were selected by produce ergot alkaloids (e.g., primarily ergovaline, but also the authors based on a previous study of dogs with DMVD [19], others such as ergosine, ergotamine, ergocornine, ergocrystine, as well as from diet histories from dogs evaluated at the authors’ and ergocrytine) [15]. Fescue toxicosis causes reproductive hospital. From these 2 sources, a list of diets was generated and issues in horses and unthriftiness in cattle, but also can have 13 individual diets were selected for analysis to represent the vascular effects in multiple species [15]. Ergot derivative drugs (i.e., larger list of diets. As this was a pilot study, strict categorization include dopamine agonists (e.g., pergolide, cabergoline) and of diets into two groups diets only eaten by dogs with DMVD anti-migraine drugs (e.g., ergotamine combined with caffeine and those only eaten by dogs without DMVD) was not possible. [Cafergot®, Migergot®] or dihydroergotamine [Migranal®]. However, a sample of canned [a-f] and dry [g-k] dog foods, as Long term use of ergot-derived medications has been associated well as two frozen raw meat-based diets [l,m] commonly eaten by with valvular heart disease in people, and is thought to be related 2B dogs with DMVD and also from dogs without DMVD was selected to activation of 5HT receptors [14,16]. Although ergotamine for this initial evaluation of variation in nutrient concentrations contamination of pet foods is unlikely with reputable pet food among diets. A single sample (1 can or approximately 250 g manufacturers that have rigorous quality control procedures, of dry or raw diet) from each selected diet was submitted for the authors are unaware of any research evaluating pet foods for analysis using only a letter code and without the label or food ergotamine derivatives. name included. A sample of each dry food and the unopened can Although factors which could result in elevated plasma and (with label removed and replaced by a letter code) were shipped valvular 5HT concentrations are an obvious dietary factor to and stored at room temperature until analysis. The raw foods evaluate, the role of other nutrients in the pathogenesis of DMVD were kept frozen at -80C (including shipment on dry ice) until also is unknown. For example, other amino acids or protein, fat, analysis. All samples were homogenized prior to analysis. and carbohydrate concentrations also could influence mitral Proximate analysis [n] was performed on all food samples so valve pathology, either directly or indirectly. Branched chain that amino acids could be converted to an energy basis and to amino acids, for example, can influence 5HT concentrations in be able to compare macronutrient concentrations among the 13 the brain because they compete with 5HT for transport across diets. Amino acids were analyzed using a commercial amino acid the blood-brain barrier. Therefore, investigation of the other analyzer [o]. Ergovaline was analyzed by HPLC [p,q,r]. Melatonin amino acids, in addition to tryptophan, may be useful to better and 5HT concentrations were analyzed by ultra-performance understand DMVD. et liquidal chromatography-Time-of-Flight mass spectrometry In addition to amino acids and the macronutrients, other (UPLC-ToF-MS) in duplicate, as previously described (Murch nutrients also may play a potential role in cardiovascular , 2010). Two samples from each food were tested for melatonin disease. Red meat’s role in human cardiovascular disease is and 5HT concentrations; all other analytes were tested in a single often attributed to its fat content and profile. However, recent sample from each food. studies have demonstrated that dietary choline and L-carnitine, Additional samples of food were required for choline and both of which are found in relatively high concentrations in free L-carnitine analysis, as these analyses were performed red meats, may be another factor contributing to the negative after the other analyses had been completed. At that time, one health effects of red meat. Dietary choline and L-carnitine are diet [m] was not available so only 12 samples were submitted metabolized by intestinal microbiota into trimethylamine, which for choline and free L-carnitine analysis. Choline was measured is further metabolized by hepatic enzymes into trimethylamine- using an enzymatic method, as previously described [20,21,s]. N-oxide (TMAO) [17,18]. Studies have shown that high TMAO Free L-carnitine was analyzed using a radioisotopic enzymatic concentrations are associated with increased risk for major method, as previously described [22,t ]. cardiovascular events (e.g., death, myocardial infarction, or stroke), even after statistical adjustment for traditional risk Data distributions were evaluated graphically and by factors [17,18]. This may be result from a suppressive effect of Kolmogorov-Smirnov tests. As many of the data were not TMAO on reverse cholesterol transport or macrophage foam cell normally distributed, data are presented as median (range). formation [17,18]. Although both choline and L-carnitine are Diet concentrations were compared to the AAFCO Dog Food often considered to have positive health benefits, there may be an Nutrient Profile minimums for macronutrients (i.e., protein, fat), interaction between these and other nutrients with the intestinal animo acids, and choline [23]. Since there is no dietary taurine microbiota which could affect cardiovascular pathology. requirement for dogs, taurine concentrations were compared to the AAFCO Cat Food Nutrient Profile minimums for taurine. Although there are a number of ways in which diet could alter Commercial statistical software was used to calculate descriptive DMVD, dietary factors that could influence the development of statisticsRESULTS [u]. AND DISCUSSION DMVD have not been investigated. Therefore, the purpose of this pilot study was to measure dietary 5HT, ergovaline, amino acids, choline, and L-carnitine as dietary factors that could be evaluated in future studies as possible factors in the pathogenesis of DMVD. One diet was below the AAFCO Dog Food Nutrient Profile minimum for fat (3.5% dry matter versus AAFCO Dog Food Nutrient
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Profile minimum of 5% dry matter) or 10.5 g/1000 kcal for the fold range in concentrations between the diet with the lowest sample versus 14.3 g/1000 kcal for the AAFCO Dog Food Nutrient tryptophan concentration (0.19% or 0.47 g/1000 kcal) and the Profile minimum).This concentration for fat also was lower than diet with the highest tryptophan concentration (0.59% or 1.32 the National Research Council (NRC) recommended allowance of g/1000 kcal). 13.8 g/1000 kcal. Other than fat for this 1 diet, all 13 diets were While much additional research is needed, it is possible that above the AAFCO minimum for all other macronutrients (Table these variable dietary concentrations could influence circulating 1). Although the protein, fat, fiber, carbohydrate, and moisture and tissue amino acid concentrations. Of particular interest is were analyzed in the food samples primarily to be able to convert the variation in tryptophan concentrations, since tryptophan amino acids to an energy basis (g/1000 kcal), it was interesting is a precursor for 5HT. However, other amino acids also could to see the variable results for macronutrients. Anecdotally, more have more indirect effects on DMVD. Taurine is not considered commercial diet options appear to be available for dogs than an essential amino acid for dogs, but taurine deficiency has been there used to be, from grain-free diets to raw meat-based diets associated with dilated cardiomyopathy in some dog breeds to vegetarian diets. This is reflected in a two-fold difference in [24-27]. It is important to note that the current pilot study protein, an eight-fold difference in fat, and diets ranging from 0 to included only a small sampling of diets from the hundreds of 173 g/1000 kcal of carbohydrate. The clinical relevance of these dog foods commercially available so it is not clear whether this variable macronutrient concentrations with respect to DMVD, is a good representation of amino acid concentrations in all dog however, is unknown. food. Further investigation of the role of dietary amino acid All 13 diets were above the AAFCO minimum for all essential concentrations on cardiac valvular concentrations is warranted. amino acids (Table 1). Taurine is not considered an essential Based on the results of recent studies which showed amino acid for dogs so there is no minimum listed in the AAFCO an association between TMAO, intestinal microbiota, and Dog Food Nutrient Profile for this nutrient. However, if the diets cardiovascular disease [17,18] dietary choline and free were compared to the AAFCO Cat Food Nutrient Profile minimum L-carnitine concentrations also were analyzed in 12 of the 13 for taurine (0.10% dry matter for extruded foods [with raw diets diets in the current pilot study. All 12 diets tested had choline likely falling into this category] and 0.20% dry matter for canned concentrations above the AAFCO Dog Food Nutrient Profile foods), 9 of the 13 diets were below the minimum (although all minimum of 1200 mg/kg dry matter (or 343 mg/1000 kcal on were at or above the NRC recommended allowance of 0.1).There an energy basis). Concentrations ranged from 1964-6228 mg/kg was a wide range in concentrations of amino acids in the 13 diets dry matter (median = 3832 mg/kg dry matter) or from 502-1398 tested. Tryptophan, for example, had an approximately three- Table 1:
Macronutrient and amino acid concentrations in dog food samples on a percent dry matter basis and on a metabolizable energy basis Diets AAFCO minimum23 Diets AAFCO minimum23 (g/1000Analytea kcal). n=13 unless otherwise noted. Presented as median (range). (% dry matter) (% dry matter) (g/1000 kcal) (g/1000 kcal)
Crude protein 32.2 (24.6-52.8) 18.0 84.5 (62.7-112.7) 51.4 Crude fat 19.6 (3.5-46.5) 5.0 46.6 (10.5-82.8) 14.3 Crude fiber 1.3 (0.3-3.7) N/A 3.0 (0.6-11.1) N/A Nitrogen-free extract 25.3 (0.0-58.3) N/A 60.1 (0.0-173.8) N/A HistidineArginine 2.29 (1.29-3.51) 0.51 4.99 (3.22-7.88) 1.46 0.77 (0.46-1.63) 0.18 1.95 (1.21-3.66) 0.51 Isoleucine 1.16 (0.82-2.61) 0.37 3.01 (2.07-5.86) 1.06 Leucine 3.12 (1.70-5.42) 0.59 6.21 (4.52-12.16) 1.69 Lysine 2.15 (1.18-4.25) 0.63 4.30 (3.10-9.50) 1.80 Methionine 0.72 (0.45-1.37) N/A 1.84 (1.33-3.00) N/A Methionine+cystine 1.13 (0.74-2.31) 0.43 2.73 (2.01-5.02) 1.23 Phenylalanine 1.47 (1.06-3.05) N/A 3.77 (2.70-6.85) N/A Phenylalanine+tyrosine 2.70 (1.93-5.46) 0.73 6.70 (4.60-12.30) 2.09 Taurine – canned (n=6)* 0.09 (0.04-0.13) 0.20* 0.20 (0.10-0.39) 0.50* Taurine – extruded/raw (n=7)* 0.12 (0.04-0.28) 0.10* 0.33 (0.11-0.60) 0.25* Threonine 1.33 (0.80-2.90) 0.48 3.14 (2.12-6.50) 1.37 Tryptophan 0.28 (0.19-0.59) 0.16 0.66 (0.47-1.32) 0.46 Tyrosine 1.22 (0.83-2.41) N/A 2.85 (1.94-5.41) N/A i.e., Valine 1.64 (1.06-3.64) 0.39 3.59 (2.63-8.17) 1.11 Key: AAFCO, Association of American Feed Control Officials; N/A, not applicable ( no AAFCO minimum established) *AAFCO Cat Food Nutrient Profile minimum (no minimums are established for taurine for dog foods) J Vet Med Res 2(5): 1035 (2015) 3/6 Freeman et al. (2015) Email:
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mg/1000 kcal (median = 871 mg/1000 kcal). Free L-carnitine would expect to have very low concentrations of both 5HT and concentrations were even more variable, ranging from 6.5- melatonin in pet food samples and that most 5HT in circulation 862.3 mg/kg dry matter (median = 57.0 mg/kg dry matter) or and tissues would be derived from conversion of tryptophan 13.9 mg/1000 kcal (range, 1.9-211.2 mg/1000 kcal). Because to 5HT. However, 5HT and melatonin are indoleamines which L-carnitine is not considered an essential nutrient, there are no appear to be signaling molecules in plants [28]. Different parts of AAFCO Dog Food Nutrient Profile minimums with which these the plants vary in concentrations of each indoleamine (e.g, 5HT values can be compared. This wide variation does not indicate is typically higher in shoots, while melatonin is higher in roots that either of these nutrients plays a role in DMVD, but their [28]. Serotonin is of interest because of its relationship to valve association with other forms of cardiovascular disease in people pathology [3,4,6,7,11] but melatonin also may have effects on makes additional research on choline and L-carnitine in dogs the cardiovascular system. Melatonin has been shown to reduce with DMVD of interest. As demonstrated in human and rodent blood pressure and also can act as a free radical scavenger [28- studies [17,18], interactions between dietary nutrients and the 30]. It is unclear to why the food samples in the current study microbiota also is an important factor to consider. contained detectable concentrations of serotonin and melatonin, but it may be related to the plant sources used in the individual All of the 13 samples tested had ergovaline concentrations diets analyzed in the current study. Further studies are needed to <100 ppb. One diet tested positive for 5HT in one duplicate (3608 determine the concentrations of these indoleamines in a larger ng/g) but only trace amounts in the other duplicate for the same sample of pet foods and any possible clinical relevance. It is food. Seven of the 13 diets had trace amounts of 5HT detected important to note that only a single can or sample of food was and in the remaining five diets, no 5HT was detectable. Nutrient analyzed, so additional testing is needed to determine variability profiles for diets positive for 5HT, diets with trace amounts of 5HT, of 5HT, melatonin, and other nutrients within a can or bag of and diets with undetectable 5HT are shown in Table 2. Melatonin food, within- and between lots, and also the effects of heating, concentrations from all 13 samples ranged from 0-1.988 mg/ cooling, and storage. kg matter (median = 0.484 mg/kg dry matter). However, if only the eight samples in which it was detected are considered, the Another major limitation to the current study is the selection median = 1.321 mg/kg (range, 0.287-1.988 mg/kg). Serotonin of diets to be analyzed. With hundreds of commercial dog foods was positive in one diet (although only in one duplicate) available, analyzing only 13 foods (and only 12 foods for choline and melatonin was detected in eight samples. Typically, one and free L-carnitine) is a very limited sample. Since this was a Table 2:
Macronutrient and amino acid concentrations in dog food samples on a metabolizable energy basis (g/1000 kcal) between diets positive for serotonin (n=1), diets with trace amounts of serotonin detected (n=7), and diets with no serotonin detected (n=5). Presented as median (range), exceptAnalyte for the diet which was positive forDiets serotonin positive in for which serotonin only the concentrationDiets with trace for the serotonin single diet detected is presented. Diets with no serotonin detected
Crude protein 86.1 88.1 (62.7-112.7) 68.9 (64.7-105.1)
Crude fat 10.5 76.0 (37.3-82.8) 42.9 (35.7-58.9)
Crude fiber 11.1 2.7 (0.6-4.5) 5.2 (2.1-8.3)
Nitrogen-free extract 173.8 33.8 (0.0-132.5) 116.2 (37.6-132.9)
ArginineHistidine 4.70 5.26 (3.22-7.88) 4.44 (3.67-6.29)
1.96 2.29 (1.32-3.66) 1.48 (1.21-2.00)
Isoleucine 3.40 3.33 (2.07-5.86) 2.59 (2.19-4.39)
Leucine 6.21 7.19 (4.71-12.16) 4.83 (4.52-8.36)
Lysine 3.99 5.94 (3.17-9.50) 3.33 (3.10-6.53)
Methionine 1.33 2.08 (1.35-3.00) 1.71 (1.39-2.52)
Methionine+cystine 2.30 3.13 (2.01-5.02) 2.71 (2.10-3.91)
Phenylalanine 4.26 3.84 (2.70-6.85) 2.91 (2.82-5.09)
Phenylalanine+tyrosine 7.68 6.70 (4.60-12.30) 5.29 (5.14-9.17)
Taurine 0.39 0.21 (0.10-0.60) 0.17 (0.11-0.60)
Threonine 3.40 3.71 (2.34-6.50) 2.41 (2.12-4.50)
Tryptophan 0.83 0.81 (0.47-1.32) 0.64 (0.61-1.02)
Tyrosine 3.43 2.85 (1.94-5.41) 2.39 (2.32-4.07)
Valine 3.90 4.63 (2.63-8.17) 3.15 (2.90-5.73) J Vet Med Res 2(5): 1035 (2015) 4/6 Freeman et al. (2015) Email:
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pilot study, the number of diets tested was limited in order to Milwaukee, WI. first determine how large a variation of results would be found m. OC Raw Dog Beef and Produce™, Mission Viejo, CA. so that future studies could be designed. Although the authors attempted to select some foods eaten by dogs with DMVD in a n. Nutrition Analysis Center, Eurofins Scientific Inc., Des Moines, previous study [19] and from diet histories of clinical cases, there IA. was not clear demarcation between diets, nor have studies been o. Amino Acid Laboratory, University of California Davis School of published identifying an association between certain diets and Veterinary Medicine, Davis, CA. DMVD. Therefore, there is the potential for bias in diet selection, and much additional research is needed to be able to determine p.University of Kentucky Veterinary Diagnostic Laboratory, any possible role of these or other nutrients in the pathogenesis Lexington, KY. of DMVD. Nonetheless, this pilot study was not designed to show q. Oregon State University Endophyte Testing Laboratory, that certain nutrients are more or less likely to cause DMVD, but Corvallis, OR. ratherCONCLUSIONS to provide hypotheses for future studies. r. Veterinary Diagnostic Laboratory, Iowa State University College of Veterinary Medicine, Ames, IA. In conclusion, data from this small pilot study suggest that, s. NPAL Laboratories, St Louis, MO. while speculative, further investigation of dietary amino acids, indoleamines, choline, and L-carnitine is warranted. Analyzing t. Metabolic Analysis Labs, Inc., Madison, WI. multiple samples from a larger distribution of diets and evaluating REFERENCESu. Systat 13.0, Systat, Chicago, IL. any possible relationships between dietary concentrations and circulating or valvular concentrations may provide interesting information that could enhance our understanding of canine 1. Fox PR, Sisson D, Moise NS (eds), Buchanan JW. Prevalence of DMVD.ACKNOWLEDGEMENTS cardiovascular disorders. In: Textbook of canine and feline cardiology, 2. 2nd ed. Philadelphia: WB Saunders. 1999; 457-470.
Atkins C, Bonagura J, Ettinger S, Fox P, Gordon S, Haggstrom J, et al. Presented in abstract form at the Waltham International Guidelines for the diagnosis and treatment of canine chronic valvular Nutritional Science Symposium, Portland, OR, October 1-4, 2013. 3. heart disease. J Vet Intern Med. 2009; 23: 1142-1150. ResearchFOOTNOTES supported by the Barkley Fund. Oyama MA, Levy RJ. Insights into serotonin signaling mechanisms associated with canine degenerative mitral valve disease. J Vet Intern 4. Med. 2010; 24: 27-36. a. Hill’s Science Diet Adult Gourmet Chicken Entrée, Hill’s Pet Orton EC, Lacerda CMR, MacLea HB. Signaling pathways in mitral Nutrition, Topeka, KS. valve degeneration. J Vet Cardiol. 2012; 14:7-17. b. Iams® ProActive Health™ Adult Chunks with Chicken and Beef 5. Harvey R, Ferrier D. Biochemistry, 5th ed. Philadelphia: Lippincott in Gravy, P&G Pet Care, Mason, OH. 6. Williams and Wilkins. 2011: 287. c. Evanger’s Vegetarian Complete Balanced Dinner, Evanger’s Oyama MA, Chittur SV. Genomic expression patterns of mitral valve tissues from dogs with degenerative mitral valve disease. Am J Vet Dog & Cat Food Company, Inc., Wheeling, IL. 7. Res. 2006; 67: 1307-1318. d. Merrick™ Classic Cowboy Cookout™, Merrick Pet Care, Inc., Ljungvall I, Höglund K, Lilliehöök I, Oyama MA, Tidholm A, Tvedten Amarillo, TX. H, et al. Serum serotonin concentration is associated with severity of myxomatous mitral valve disease in dogs. J Vet Intern Med. 2013; 27: e. Mighty Dog Hearty Beef Dinner, Nestle Purina Pet Care, St. 8. 1105-1112. Louis, MO. Hutcheson JD, Setola V, Roth BL, Merryman WD. Serotonin receptors f. Wellness Lamb and Sweet Potato Recipe, WellPet, Tewksbury, and heart valve disease – It was meant to 2B. Pharmacol Ther. 2011; MA 9. 132: 146-157. g. Beneful Original, Nestle Purina Pet Care, St. Louis, MO. Levy RJ. Serotonin transporter mechanisms and cardiac disease. 10. Circulation. 2006; 113: 2-4. h. Blue™ Life Protection Formula Chicken and Rice Recipe, Blue Buffalo Co., Wilton, CT. Lacerda CMR, MacLea HB, Kisiday JD, Orton EC. Static and cyclic tensile strain induce myxomatous effector proteins and serotonin in i. Evo Red Meat Formula, Natura Pet Products, Inc., Freemont, 11. canine mitral valves. J Vet Cardiol. 2012; 14: 223-230. NE. Disatian S, Orton E. Autocrine serotonin and transforming growth j. Nutro Natural Choice Limited Ingredient Diet Lamb and factor beta 1 signaling mediates spontaneous myxomatous mitral 12. valve disease. J Heart Valve Dis. 2009; 18: 44-51. Whole Brown Rice Formula, The Nutro Company, Mars, Inc., Franklin, TN Arndt JW, Reynolds CA, Singletary GE, Connolly JM, Oyama MA. Serum serotonin concentrations in dogs with degenerative mitral valve k. Royal Canin Veterinary Diet Early Cardiac™, Royal Canin USA, 13. disease. J Vet Intern Med. 2009; 23: 1208-1213. St. Charles, MO. Koopmans SJ, Guzik AC, van der Meulen J, Dekker R, Kogut J, Kerr BJ, l. Stellas Super Beef™ Frozen Dinner, Stella & Chewy’s , et al. Effects of supplemental L-tryptophan on serotonin, cortisol, J Vet Med Res 2(5): 1035 (2015) 5/6 Freeman et al. (2015) Email:
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intestinal integrity, and behavior in weanling piglets. J Anim Sci. 2006; 22. 1999: Gaithersburg, MD. 14. 84: 963-971. Parvin R, Pande SV. Microdetermination of (-) carnitine and carnitine Horvath J, Fross RD, Kleiner-Fisman G, Lerch R, Stalder H, Liaudat S, acetyl transferase. Analytical Biochem. 1977; 79: 190-201. et al. Severe multivalvular heart disease: A new complication of the 23. Association of American Feed Control Officials. Official publication. ergot derivative dopamine agonists. Movement Disorders. 2004; 19: West Lafayette, Ind: Association of American Feed Control Officials, 656-662. 24. Inc, 2014: 135-148. 15. Evans TJ, Blodgett DJ, Rottinghaus GE. Fescue toxicosis. In Gupta RC Kittleson MD, Keene B, Pion PD, Loyer CG. Results of the multicenter (ed.) Veterinary toxicology, 2nd ed. Salt Lake City: Academic Press, 25. spaniel trial (MUST). J Vet Intern Med. 1997; 11: 204-211. 16. 2012: 1166-1177. Alroy J, Rush J, Freeman L, Kuman A, Karuri A, Chase K, et al. Inherited Redfield M, Nicholson W, Edwards W, Tajik AJ. Valve disease infantile dilated cardiomyopathy in dogs: Genetic, clinical, biochemical, associated with ergot alkaloid use: Echocardiographic and pathologic 26. and morphological findings. Am J Med Genetics. 2000; 95: 57-66. 17. correlations. Ann Intern Med. 1992; 117: 50-52. Fascetti AJ, Reed JR, Rogers QR, Backus RC. Taurine deficiency in dogs Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, et al. with dilated cardiomyopathy: 12 cases (1997-2001). J Am Vet Med Intestinal microbiota metabolism of L-carnitine, a nutrient in red 27. Assoc. 2003; 223: 1137-1141. 18. meat, promotes atherosclerosis. Nature Med. 2013; 19: 576-585. Backus RC, Cohen G, Pion PD, Good KL, Rogers QR, Fascetti AJ. 2003. Tang WHW, Wang Z, Levison BS, Koeth RA, Britt EB, Fu X, et al. Intestinal Taurine deficiency in Newfoundlands fed commercially available microbial metabolism of phosphatidylcholine and cardiovascular risk. complete and balanced diets. J Am Vet Med Assoc. 2003; 223: 1130- New Engl J Med. 2013; 368: 1575-1584. 28. 1136. 19. Trafny DJ, Freeman LM, Bulmer BJ, MacGregor JM, Rush JE, Meurs Murch SJ, Hall BA, Le CH, Saxena PK. Changes in the levels of KM, et al. Auscultatory, echocardiographic, biochemical, nutritional, indoleamine phytochemicals during véraison and ripening of wine and environmental characteristics of mitral valve disease in Norfolk 29. grapes. J Pineal Res. 2010; 49: 95-100. 20. terriers. J Vet Cardiol. 2012; 14: 261-267. Allegra M, Reiter RJ, Tan DX, Gentile C, Tesoriere L, Livrea MA. The Woollard DC, Indyk HE. Determination of choline in milk and infant chemistry of melatonin’s interaction with reactive species. J Pineal formulas by enzymatic analysis: Collaborative study. J AOAC Intl. 30. Res. 2003; 34: 1-10. 2000; 83: 131-138. Reiter RJ, Tan D-X, Paredes SD, Fuentes-Broto L. Beneficial effects of 21. AOAC. AOAC Official Method 999.14. Choline in infant formula and milk melatonin in cardiovascular disease. Ann Med. 2010; 42: 276-285. enzymatic colorimetric method. Methodology for AOAC International.
Cite this article Sauer JL, Freeman LM, Rush JE (2015) A pilot study investigating dietary factors with possible associations with canine degenerative mitral valve disease. J Vet Med Res 2(5): 1035.
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