Key nutrients important in the management of canine myxomatous mitral valve disease and heart failure.

The most common cause of heart failure in dogs is myxomatous mitral valve disease (MMVD), which accounts for approximately 75% of canine heart disease cases and is especially common in smaller dogs. Although low-sodium diets have been recommended for humans with heart diseases for decades, there is little evidence to support this practice in dogs. In recent years, however, it has become clear that other nutrients are important to heart health. Dogs with heart disease secondary to MMVD experience patterns of metabolic changes that include decreased mitochondrial energy metabolism and ATP availability, with increased oxidative stress and inflammation. These changes occur early in disease and progress with worsening heart disease. Key nutrients that may support normal function and address these changes include omega-3 fatty acids, medium-chain triglycerides, magnesium, antioxidants including vitamin E and taurine, and the amino acids methionine and lysine. The long-chain omega-3 fatty acids provide anti-inflammatory, antithrombotic, and other benefits. Medium-chain fatty acids and ketones derived from medium-chain triglycerides provide an alternative energy source for cardiac mitochondria and help reduce free radical production. Magnesium supports mitochondrial function, normal cardiac rhythm, and provides other benefits. Both vitamin E and taurine counter oxidative stress, and taurine also has direct cardiac benefits. Dogs with MMVD have reduced plasma methionine. Methionine and lysine are important for carnitine production as well as other functions. This article reviews the evidence supporting the functions and benefits of these and other nutrients in MMVD and other cardiac conditions.

Serum untargeted metabolomic changes in response to diet intervention in dogs with preclinical myxomatous mitral valve disease.

Myocardial energy deprivation plays a causal role in the development of heart failure. A cardiac protection blend (CPB) of nutrients including medium chain triglycerides, fish oil and other key nutrients was developed to slow the progression of canine myxomatous mitral valve disease (MMVD). A six-month dietary intervention demonstrated efficacy of CPB in slowing MMVD progression. Untargeted metabolomic analysis of serum from these dogs identified 102 differential metabolites (adjusted P < 0.05). The ratios of omega-6 to omega-3 fatty acid (FA) changed from 2.41 and 1.46 in control and CPB groups at baseline to 4.30 and 0.46 at 6 months respectively. A 2.7-fold increase of α-aminobutyrate, a myocardial modulator of glutathione homeostasis, was found in CPB dogs compared to 1.3-fold increase in control dogs. Arginine and citrulline, precursors of nitric oxide biosynthesis, were both increased 2-fold; caprate, a medium chain FA, was increased 3-fold; and deoxycarnitine, precursor of carnitine biosynthesis, was increased 2.5-fold in CPB dogs. Margarate and methylpalmitate decreased in response to CPB, a potential benefit in MMVD dogs as positive correlations were found between changes in both these FAs and left atrial diameter (r = 0.69, r = 0.87 respectively, adjusted P < 0.05). Sphingomyelins with very long chain saturated FAs associated with decreased risk of heart failure in humans were increased in MMVD dogs fed the CPB diet. Our data supports the hypothesis that CPB improves FA utilization and energetics, reduces oxidative stress and inflammation in MMVD dogs. More studies are needed to understand the roles of specific metabolites in MMVD.

Dietary intervention reduces left atrial enlargement in dogs with early preclinical myxomatous mitral valve disease: a blinded randomized controlled study in 36 dogs.

BACKGROUND: Myxomatous mitral valve disease (MMVD), the most common naturally-occurring heart disease in dogs, is associated with alterations in energy metabolism, oxidative stress and inflammation. Energy deprivation plays a causal role in the development of heart failure. This study was designed to determine if a cardiac protection blend (CPB) of nutrients containing medium-chain triglycerides as an alternative energy source, fish oil to reduce inflammation, antioxidants, and other key nutrients important to cardiac health and function could slow or prevent MMVD progression. Nineteen dogs with early stage MMVD and 17 breed-, age-, and sex-matched healthy dogs were enrolled for a 6-month blinded, placebo-controlled study. Dogs in each cardiac health group were randomly assigned to either control diet (CON) or CPB-supplemented diet. Echocardiography was performed at baseline, 3 months and 6 months. RESULTS: No changes were found in healthy dogs. While MMVD-CON dogs had an average 10% increase over baseline in left atrial diameter (LAD) and left atrial to aortic root ratio (LA/Ao) at 6 months, MMVD-CPB dogs showed 3% decreases, resulting significant diet by time interactions (P = 0.037, P = 0.005, respectively). More MMVD-CON dogs progressed from stage B1 to B2 during the study. A positive correlation was found between 6-month changes in LAD and blood pressures in MMVD-CPB dogs (systolic: P = 0.050, diastolic: P = 0.035) but not MMVD-CON dogs. CONCLUSIONS: Our results demonstrated efficacy of CPB-based dietary intervention in reducing LA size and mitral regurgitation, and in slowing or preventing the progression of early MMVD in dogs.

Veterinary Medicine and Multi-Omics Research for Future Nutrition Targets: Metabolomics and Transcriptomics of the Common Degenerative Mitral Valve Disease in Dogs.

Canine degenerative mitral valve disease (DMVD) is the most common form of heart disease in dogs. The objective of this study was to identify cellular and metabolic pathways that play a role in DMVD by performing metabolomics and transcriptomics analyses on serum and tissue (mitral valve and left ventricle) samples previously collected from dogs with DMVD or healthy hearts. Gas or liquid chromatography followed by mass spectrophotometry were used to identify metabolites in serum. Transcriptomics analysis of tissue samples was completed using RNA-seq, and selected targets were confirmed by RT-qPCR. Random Forest analysis was used to classify the metabolites that best predicted the presence of DMVD. Results identified 41 known and 13 unknown serum metabolites that were significantly different between healthy and DMVD dogs, representing alterations in fat and glucose energy metabolism, oxidative stress, and other pathways. The three metabolites with the greatest single effect in the Random Forest analysis were γ-glutamylmethionine, oxidized glutathione, and asymmetric dimethylarginine. Transcriptomics analysis identified 812 differentially expressed transcripts in left ventricle samples and 263 in mitral valve samples, representing changes in energy metabolism, antioxidant function, nitric oxide signaling, and extracellular matrix homeostasis pathways. Many of the identified alterations may benefit from nutritional or medical management. Our study provides evidence of the growing importance of integrative approaches in multi-omics research in veterinary and nutritional sciences.

Expression Profiling of Circulating MicroRNAs in Canine Myxomatous Mitral Valve Disease.

MicroRNAs (miRNAs) are small non-coding RNAs that have shown promise as noninvasive biomarkers in cardiac disease. This study was undertaken to investigate the miRNA expression profile in dogs with myxomatous mitral valve disease (MMVD). 277 miRNAs were quantified using RT-qPCR from six normal dogs (American College of Veterinary Internal Medicine Stage A), six dogs with MMVD mild to moderate cardiac enlargement (ACVIM Stage B1/B2) and six dogs with MMVD and congestive heart failure (ACVIM Stage C/D). Eleven miRNAs were differentially expressed (False Discovery Rate < 0.05). Dogs in Stage B1/B2 or C/D had four upregulated miRNAs, including three cfa-let-7/cfa-miR-98 family members, while seven others were downregulated, compared to Stage A. Expression of six of the 11 miRNAs also were significantly different between dogs in Stage C/D and those in Stage B1/B2. The expression changes were greater as disease severity increased. These miRNAs may be candidates for novel biomarkers and may provide insights into genetic regulatory pathways in canine MMVD.

Discrepancy between use of lean body mass or nitrogen balance to determine protein requirements for adult cats.

This study was undertaken to contrast the minimum protein intake needed to maintain nitrogen balance or lean body mass (LBM) in adult cats using a prospective evaluation of 24 adult, neutered male cats fed one to three different diets. Following a 1-month baseline period during which all cats consumed a 34% protein diet, cats were fed a 20% (LO), 26% (MOD) or 34% (HI) protein diet for 2 months. During the baseline period and following the 2-month feeding period, nitrogen balance was assessed using a 96-h complete collection of urine and feces, and LBM was assessed using dual energy X-ray absorptiometry. Weight loss increased in a linear manner with decreasing protein intake (P <0.01), despite no significant difference in calorie intake. Linear regression of the data indicated that approximately 1.5 g protein/kg (2.1 g/kg(0.75)) body weight is needed to maintain nitrogen balance, while 5.2 g protein/kg (7.8 g/kg(0.75)) body weight is needed to maintain LBM. This study provides evidence that nitrogen balance studies are inadequate for determining optimum protein requirements. Animals, including cats, can adapt to low protein intake and maintain nitrogen balance while depleting LBM. Loss of LBM and an associated reduction in protein turnover can result in compromised immune function and increased morbidity. Current Association of American Feed Control Officials (AAFCO) and National Research Council (NRC) standards for protein adequacy may not provide adequate protein to support LBM. The minimum daily protein requirement for adult cats appears to be at least 5.2 g/kg (7.8 g/kg(0.75)) body weight, well in excess of current AAFCO and NRC recommendations. Further research is needed to determine the effect, if any, of body condition, age and gender on protein requirements.

Evaluation of canned therapeutic diets for the management of cats with naturally occurring chronic diarrhea.

Dietary therapy plays an important role in the management of most gastrointestinal disorders. This study was designed to test the efficacy of a new therapeutic diet for cats with diarrhea, compared to the top selling brand. Sixteen adult cats with chronic diarrhea were grouped and assigned to diet X (Hill's Prescription Diet i/d Feline) or diet Y (Purina Veterinary Diets EN Gastroenteric Feline Formula). Following baseline evaluations, cats were fed their assigned test diet for 4 weeks. Fecal scores (FS; 7=very watery; 1=extremely dry and firm) were recorded daily during the last week on each diet. Each cat was then switched to the alternate test diet and the procedure was repeated. Fifteen cats completed the study. Both therapeutic diets resulted in a significant improvement in average FS and diet Y also resulted in significantly better results compared with diet X. Average FS improved at least one unit in 40% of the cats while fed diet X and in 67% of the cats while fed diet Y, resulting in normal stools (average FS≤3) in 13.3% of cats fed diet X and 46.7% of cats fed diet Y. This study confirms the value of dietary change in the management of chronic diarrhea in cats.

The effects of weight loss on adipokines and markers of inflammation in dogs.

Evidence suggests that adipose tissue-derived adipokines induce mild inflammation and may play a role in insulin resistance associated with diabetes. The present study was designed to examine a series of adipokines and markers of inflammation in dogs before and after a successful weight loss. The study included fasting serum samples from twenty-five dogs before and after a weight-loss programme. Serum C-reactive protein (CRP) and monocyte chemoattractant protein-1 (MCP-1) were measured as indicators of chronic inflammation, while serum adipokines including total adiponectin, high-molecular-weight (HMW) adiponectin, resistin and leptin were also examined. Medians for CRP (before, 10.0 (interquartile range 5.4-15.0) µg/ml; after, 5.6 (interquartile range 3.8-7.0) µg/ml) and MCP-1 (before, 212 (interquartile range 157-288) ng/ml; after, 185 (interquartile range 143-215) ng/ml) decreased significantly after weight loss. Medians for resistin showed a mild, yet significant reduction (before, 67.1 (interquartile range 44.4-88.5) pg/ml; after, 60.5 (interquartile range 32.3-67.1) pg/ml), while leptin showed a dramatic decrease after weight loss (before, 18.9 (interquartile range 10.8-35.4) ng/ml; after, 6.6 (interquartile range 3.9-10.2) ng/ml). Serum total adiponectin and HMW adiponectin were unchanged on all analyses performed. These data suggest that weight loss can decrease chronic inflammation; however, the clinical implications of this decrease are not well elucidated in dogs. Surprisingly, there was no increase in total or HMW serum adiponectin after weight loss, as observed previously in human subjects. The lack of change in total and HMW adiponectin might explain why insulin resistance and type 2 diabetes are less prevalent in obese dogs when compared with humans and cats.

Correlation of a feline muscle mass score with body composition determined by dual-energy X-ray absorptiometry.

Body condition scoring (BCS) systems primarily assess body fat. Both overweight and underweight animals may have loss of lean tissue that may not be noted using standard BCS systems. Catabolism of lean tissue can occur rapidly, may account for a disproportionate amount of body mass loss in sick cats and can have deleterious consequences for outcome. Therefore, along with evaluation of body fat, patients should undergo evaluation of muscle mass. The aims of the present study were first to evaluate the repeatability and reproducibility of a 4-point feline muscle mass scoring (MMS) system and second to assess the convergent validity of MMS by dual-energy X-ray absorptiometry (DXA). MMS was as follows: 3, normal muscle mass; 2, slight wasting; 1, moderate wasting; 0, severe wasting. For the first aim, forty-four cats were selected for evaluation based on age and BCS, and for the second aim, thirty-three cats were selected based on age, BCS and MMS. Cats were scored by ten different evaluators on three separate occasions. Body composition was determined by DXA. Inter- and intra-rater agreement were assessed using kappa analysis. Correlation between MMS and BCS, age, percentage lean body mass and lean body mass (LBM) was determined using Spearman's rank-order correlation. The MMS showed moderate inter-rater agreement in cats that scored normal or severely wasted (κ = 0.48-0.53). Intra-rater agreement was substantial (κ = 0.71-0.73). The MMS was significantly correlated with BCS (r 0.76, P < 0.0001), age (r - 0.75, P < 0.0001), LBM (g) (r 0.62, P < 0.0001) and percentage LBM (r - 0.49, P < 0.0035). Additional investigation is needed to determine whether the MMS can be refined and to assess its clinical applicability.

Effects of dietary sodium chloride on health parameters in mature cats.

High sodium diets have been shown to enhance water intake and urine output, a potential benefit in the management of lower urinary tract diseases. However, one study suggested that high salt (sodium chloride) diets might have adverse effects on the kidneys [Kirk CA, Jewell DE, Lowry SR. Effects of sodium chloride on selected parameters in cats. Vet Ther 2006; 7: 333-46]. Therefore, the objective of this controlled, prospective study was to evaluate the effects of diets with different salt content (1.11% sodium and 1.78% chloride versus 0.55% sodium and 1.02% chloride, dry matter (dm)) when fed to mature cats (mean age 7.0 years; 12 cats per group) over a 6-month period. Food intake, body weight, bone mineral content, total body hydration status, blood pressure, and markers of renal function were unaffected by salt intake, and no adverse effects were observed. When a subset of cats (n=9) with an initial serum creatinine > or =1.6mg/dl was evaluated separately, there remained no evidence of adverse effects associated with increased salt intake. These results are consistent with the majority of other studies evaluating sodium intake in cats, as well as with the National Research Council's assessment, all of which indicate that sodium at 1.5% of the diet dm is not harmful to healthy cats.

Disease prevalence among dogs and cats in the United States and Australia and proportions of dogs and cats that receive therapeutic diets or dietary supplements.

OBJECTIVE: To estimate disease prevalence among dogs and cats in the United States and Australia and proportions of dogs and cats that receive therapeutic diets or dietary supplements. DESIGN: Telephone survey. Sample Population-Dog and cat owners located in 5 geographic areas. PROCEDURES: A telephone survey was administered to dog and cat owners. RESULTS: Of 18,194 telephone calls that were made, 1,104 (6%) were to individuals who owned at least 1 dog or cat and agreed to participate. Information was collected for 635 dogs and 469 cats. Only 14 (1%) respondents indicated that their pet was unhealthy, but 176 (16%) indicated that their pets had 1 or more diseases. The most common diseases were musculo-skeletal, dental, and gastrointestinal tract or hepatic disease. Many owners (n = 356) reported their pets were overweight or obese, but only 3 reported obesity as a health problem in their pets. Owners of 28 (2.5%) animals reported that they were feeding a therapeutic diet, with the most common being diets for animals with renal disease (n = 5), reduced-calorie diets (5), and reduced-fat diets (4). Owners of 107 of 1,076 (9.9%) animals reported administering dietary supplements to their pets. Multivitamins (n = 53 animals), chondroprotective agents (22), and fatty acids (13) were the most common dietary supplements used. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that most dogs and cats reported by their owners to have a health problem were not being fed a therapeutic diet. In addition, the rate of dietary supplement use was lower than that reported for people.

Nutrition for aging cats and dogs and the importance of body condition.

Before recommending a diet for a senior pet, a thorough nutritional evaluation should be completed. Although many middle-aged and older pets are overweight, a large percentage of geriatric cats and dogs have a low BCS. Approximately one third of cats older than 12 years of age may have a decreased ability to digest fat, whereas one in five may have a compromised ability to digest protein. Thus, appropriate diets for these two age groups may differ considerably. Mature (middle-aged) cats would likely benefit from a lower calorie food, whereas geriatric cats (>12 years of age) may need a highly digestible nutrient-dense diet. More than 40% of dogs between the ages of 5 and 10 years are overweight or obese. Such dogs may benefit from diets with lower fat and calories. Senior dogs also have an increased need for dietary protein, however. Therefore, healthy older dogs may benefit from diets with an increased protein-to-calorie ratio, providing a minimum of 25% of calories from protein. Common obesity-related conditions in dogs or cats include DM and OA. Diabetes differs between dogs and cats. Type I diabetes, common in dogs, seems to respond to fiber-enriched diets, whereas type II diabetes, common in cats, seems to benefit from high-protein and low-carbohydrate diets. OA, an inflammatory condition that occurs in approximately 20% of dogs, may benefit from weight management and nutrients that reduce the inflammatory responses, such as long-chain n-3 fatty acids.

Comparison of various methods for estimating body fat in dogs.

Obesity is considered one of the most common forms of malnutrition occurring in dogs. Laboratory methods of evaluation of body composition in live dogs have included dual-energy X-ray absorptiometry (DEXA) and deuterium oxide (D(2)O) dilution. Clinical methods of evaluation include assigning a body condition score (BCS) based on visual observation, palpation, and morphometric measurements. This study used these four methods to evaluate 23 healthy, adult, client-owned dogs. Good correlation (coefficient of determination [r(2)]=0.78) was found between measurements of percent body fat (%BF) determined by the D(2)O dilution method and the DEXA scan. Percent body fat can also be estimated using BCS (r(2)=0.92 comparison with DEXA) or by using morphometric measurements with simple calculations (r(2)=0.92 comparison with DEXA).