David S. Kronfeld

Insulin Resistance in Equids: Possible Role in Laminitis

Insulin is a major regulatory hormone in glucose and fat metabolism, vascular function, inflammation, tissue remodeling, and the somatotropic axis of growth. Insulin resistance alters insulin signaling by decreasing insulin action in certain resistant pathways while increasing insulin signaling in other unaffected pathways via compensatory hyperinsulinemia. In humans, altered insulin signaling is implicated in reduced glucose availability to insulin-sensitive cells, vasoconstriction and endothelial damage, and inflammatory response. Although no direct evidence exists for insulins role in these mechanisms in the laminitic horse, changes in the glucose availability, vasculature, and inflammation were all demonstrated in hoof separation. Insulin resistance was first implicated in the pathogenesis of laminitis in the 1980s using tolerance tests. Our present findings provide the first specific evidence of insulin resistance as a major predisposing condition for laminitis. Specific quantitative characterization of insulin resistance is essential toward identifying the following: 1) ponies in need of special management to avoid laminitis, and 2) potential management strategies to avoid laminitis by increasing insulin sensitivity, including reducing obesity, increasing exercise, and moderating dietary carbohydrates, particularly starch.

Optimal Nutrition for Athletic Performance, with Emphasis on Fat Adaptation in Dogs and Horses

Four mathematical approaches are proposed to determine optimal ranges of nutrients for specified purposes. For exercise, the diet must provide optimal mixtures of fuels, also optimal amounts of nutrients conducive to a sound structure, a desired power/weight ratio, a water-electrolyte system that resists dehydration and buffers hydrogen ions, a tolerance to the cumulative stress of repetitive competition and tractable attitude. The nutritional strategy of carbohydrate loading risks a variety of abnormalities in dogs and horses. An alternative strategy of fat adaptation (the combination of fat feeding and training) was found to improve aerobic performance in dogs and horses and to spare glycogen utilization and reduce lactate accumulation. Surprisingly, improved anaerobic performance has also been confirmed in fat-adapted horses that have been sprint trained. Fat adaptation increased the blood lactate responses to incremental tests and repeated sprints. Blood lactate accumulation during repeated sprints was affected synergistically by the combination of fat adaptation and sodium bicarbonate supplementation. Fat adaptation in horses appears to facilitate metabolic regulation to achieve power needs, with glycolysis decreasing during aerobic work but increasing during anaerobic work and with blood lactate changes following accordingly. Interactions between fat adaptation and dietary cation-anion balance need further investigation.

Antioxidant Status of Horses during Two 80-km Endurance Races

Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA; *Rectortown Equine Center, Rectortown, VA; †Department of LACS, Phase II, Virginia Maryland Regional College of Veterinary Medicine, Blacksburg, VA; ‡Department of Animal Sciences, Hebrew University, Rehovot, Israel and §Equine Studies Group, Waltham Centre for Pet Nutrition and Care, Leicestershire, UK

Dietary Aspects of Developmental Orthopedic Disease in Young Horses

The clinician may choose between two approaches to nutritional intervention. One is to evaluate the ration and make a painstaking effort to identify those specific factors operating in a particular case, then correct them. The second is to evaluate the ration, inspect for obvious aberrations, and, if finding none, proceed with no further delay to formulate an optimal diet, or a series, for the animals, and design a feeding program to suit farm management. Veterinarians should counsel clients on the possible or probable consequences of level of feeding on growth rate and clinical expression of DOD. In our view, retardation of growth rate by feeding poor quality hay is irresponsible. At present, we suggest that the new approach to retarded growth in weanlings and yearlings--a carefully formulated diet that specifically restricts starch and protein while supplying NRC minimum requirements of other essential nutrients--should be confined to selected individuals and be conducted under strict professional supervision.

Comparison of oxidative stress and antioxidant status in endurance horses in three 80-km races

This study tested our hypothesis that during an 80-km Research Ride in 2002 (R2) horses that did not finish (NF) the ride would have elevated muscle enzyme activities in the blood and changes in biomarkers of oxidative stress as compared to horses that finished (F) the ride. These results were then compared to previous rides – Old Dominion (OD) and the Research Ride 2001 (R1). For R2, 40 mostly Arabian horses competed and had blood samples collected before, at 27, 48 and 80 km, and 170 to 190 min after the 80-km race. Blood was collected similarly in R1 and OD. Blood was analysed for plasma lipid hydroperoxides (LPO), α-tocopherol (TOC), creatine kinase (CK), aspartate aminotransferase (AST), red and white blood cell total glutathione (GSH-T) and glutathione peroxidase (GPx). Data were analysed using a repeated measure ANOVA in SAS. Associations between muscle enzymes and antioxidant status were determined using Pearsons or Spearmans correlations. Activities of CK and AST were higher ( P r = −0.21; P = 0.005), GPx and AST ( r = −0.15; P = 0.05), and a positive correlation was found with GSH-T and CK ( r = 0.18; P = 0.02). Values of CK, LPO, GPx and GSH-T were higher ( P

Protein status of exercising Arabian horses fed diets containing 14% or 7.5% crude protein fortified with lysine and threonine

Abstract Ten Arabian horses (5 mares and 5 geldings averaging 436±17 kg) were randomly assigned to one of two dietary treatments: LP (7.5% CP fortified with 0.5% lysine and 0.3% threonine) or HP (14.5% CP). Diet composition and nutrient content are shown in Table 1.Horses were conditioned for nine weeks, then an exercise test was performed. It consisted of a warm-up followed by six, one-minute sprints at 10 m/s separated by four minutes of walking on a 6% slope. It concluded with a 30-minute recovery at the walk. Blood samples were taken every two weeks during the conditioning period as well as at rest, during the last 15 seconds of each sprint and at 5, 10, 20 and 30 minutes of recovery during the exercise test. Urine samples were obtained from mares every two weeks. Blood samples were analyzed for albumin, total protein, plasma urea-N (PUN) and creatinine. Urine was analyzed for urea, uric acid and creatinine. Horses were observed daily for clinical signs of protein deficiency. Effects of diet and time were evaluated by analysis of variance with repeated measures. During the conditioning period, there was no effect of diet on plasma albumin (P = .25), total protein (P = .72) or creatinine (P = .21). All values were within the normal ranges reported for horses. There was an effect of diet on PUN (P = .0001) with horses in the high protein group exhibiting greater PUN levels than horses in the low protein group. No difference in urine creatinine levels (P = .78) were observed. Urine urea (P = 0.011) as well as uric acid (P = 0.0001) were lower in the low protein group than in the high protein group. These differences are expected as a reflection of the different protein levels in the diet. During the exercise test, no differences in plasma albumin (P = .32), total protein (P = .81) or creatinine (P = .39) were observed. A greater PUN persisted in the high protein group (P = .0001). This was expected due to the difference in dietary nitrogen. No detrimental effect of the lower level of protein, fortified with amino acids, on protein status was observed during this experiment based on the measurements in this study. These results indicate that the restricted protein level fortified with limiting amino acids was adequate for conditioning and exercise over the nine weeks of the experiment. In a companion study, the lower level of protein fortified with amino acids moderated the acid-base responses to repeated sprints. 1

Lipoic Acid as an Antioxidant in Mature Thoroughbred Geldings: A Preliminary Study

alpha-Lipoic acid (LA) has demonstrated antioxidant effects in humans and laboratory animals. The objective of this study was to determine whether the effects of LA are similar in horses. Five Thoroughbred geldings were supplemented with 10 mg/kg/d DL-alpha-lipoic acid in a molasses and sweet feed carrier and five received only the carrier as a placebo (CON). Blood samples were obtained at baseline (0 d), after 7 and 14 d of supplementation, and 48 h postsupplementation (16 d). Blood fractions of red and white blood cells (RBC and WBC, respectively) and plasma were analyzed for glutathione (GSH), glutathione peroxidase (GPx) and total plasma lipid hydroperoxides (LPO). An experienced veterinarian observed no adverse clinical effects. Plasma LPO baselines differed between groups (P = 0.002). When covariates were used, there was a decrease over time in the LA group (P = 0.015) and concentrations were lower in the LA group than in the CON group at 7 and 14 d (P = 0.022 and P = 0.0002, respectively). At baseline, GSH concentration was 69 +/- 7 in WBC and 115 +/- 13 mmol/mg protein in the RBC, with no differences resulting from either time or treatment. The GPx activity was 47 +/- 4 and 26 +/- 5 U/g protein at baseline WBC and RBC, respectively, with a lower concentration in the LA groups WBC at 7 (P = 0.019) and 14 d (P = 0.013). The results show that 10 mg/kg LA had no evident adverse effects, and moderately reduced the oxidative stress of horses allowed light activity. These findings encourage studying of LA in horses subjected to strenuous exercise.

Acceptance of fat and lecithin containing diets by horses

Abstract Fats have been included in equine diets to increase energy density, replace carbohydrates, diminish excitability and improve athletic performance. Previous experiments have demonstrated the acceptability of corn oil, and the present studies compared the acceptability of various fats to that of corn oil. In three trials, ten fat containing concentrates were fed to horses in cafeteria-style preference trials and ranked from highest to lowest as follows: corn oil, blend no. 3, hydrolyzed tallow, peanut oil, safflower oil, blend no. 2, blend no. 1, cottonseed oil, inedible tallow and fancy bleached tallow. In two trials, acceptabilities of lecithin-containing diets were compared. Mixtures were preferred according to the increasing amounts of corn oil. Soy lecithins and corn lecithins had similar acceptances. These studies demonstrated the superior palatability of corn oil for horses.

Body fluids and exercise: Replacement strategies

Abstract Athletic performance is initially enabled but then becomes limited by changes in body fluids. This review deals with potentially beneficial interventions replacement strategies. It is the second of a trilogy on exercise with a focus on body fluids. The first part (published previously in this Journal) concerned physiological changes in body fluids likely to affect performance. These changes are certain to tax the homeostatic capacity of a competitive horse, which may be supported by supplementation with water and electrolytes before, during or after an event. The simplest replacement strategy is to completely offset depletion, so as to maintain or restore the resting status. A preferred replacement strategy emphasizes more frequent and smaller doses during an event, so as to avoid over-riding the initial beneficial changes in body fluids. Because the turning points from enabling to limiting are not well established, effective electrolyte replacement currently depends as much on the riders development of a specific dosage regimen (amounts and times) for an individual horse as on any scientists rational design of a flexible formula for all horses.Marketedformulas are based on sweat loss and changes in plasma. Most contain Na, K and Cl; some also have Ca, Mg, P, glucose and nutraceuticals. Attention to hyperkalemia at speeds over 4 m/s suggests the need for two formulas—one without potassium for use during an event, the other with potassium for use before and after. Illustrative studies are examined for the validity of their physiological interpretations and their practicalimplications. They indicate various advantages from the administration of hypertonic mixtures of electrolytes in pastes or slurries a few hours before as well as during and after an event, provided that the horse has ample opportunity to drink. Nevertheless, the physiology of absorption suggests that hypertonic mixtures should be regarded as unsuitable for a clinically hypohydrated horse until shown otherwise. The third part of this series will discuss the influence of nutrition and feeding management on body fluids and performance.

Acid–base responses of fat-adapted horses: relevance to hard work in the heat

Abstract Feeding and training may affect acid–base responses to strenuous exercise. Acidosis usually correlates with higher blood lactate concentrations during intense exercise, but alkalosis has been found in several studies of horses, and higher lactate responses during sprints have been found in fat adapted horses. To elucidate these unexpected findings, we applied a comprehensive physicochemical approach to evaluate acid–base responses during exercise in fat adapted horses. In incremental tests and repeated sprints, changes in blood [H + ] were dependent upon corresponding changes in p CO 2 but not strong ion difference (SID, the algebraic sum of ions of sodium, potassium, chloride and lactate). The influence of changes in [Lac − ] were largely offset by changes in [Na + ], [K + ] and [Cl − ], so that SID was unchanged and did not contribute to the exercise induced acidemia, so it may be inaccurate to term this a lacticacidosis. During repeated sprints, central venous [H + ] increased (acidosis) but arterial [H + ] decreased (alkalosis). These changes were consistent with concurrent changes in venous and arterial p CO 2 but not SID. Fat adaptation decreased mixed venous p CO 2 during repeated sprints, which is consistent with the lower respiratory quotient associated with fat oxidation. Less pulmonary work to eliminate CO 2 could benefit horses under hot and humid conditions, especially those with mildly reduced pulmonary function. The blood lactate response was decreased during aerobic tests but increased during anaerobic tests on fat adapted horses. Fat adaptation appears to facilitate the metabolic regulation of glycolysis, by sparing glucose and glycogen at work of low intensity, but by promoting glycolysis when power is needed for high intensity exercise. The blood lactate response to repeated sprints was increased more by the combination of fat adaptation and oral supplementation of sodium bicarbonate than by the sum of the responses to fat alone or bicarbonate alone. This synergism suggests that need for further studies of the interaction of fat adaptation with dietary cation–anion balance, especially under hot conditions. These results integrate harmoniously with previous findings of lower feed intake and fecal output, lower loads of heat and CO 2 , lower water losses in the feces and by evaporation, and less spontaneous activity and reactivity in fat adapted horses. Thus fat adaptation confers several advantages on horses and presumably other equids used for hard work, especially in the heat.