Frank Andrews is a graduate of Washington State University College of Veterinary Medicine. He completed an equine medicine and surgery residency at

Transcription

1 Frank Andrews is a graduate of Washington State University College of Veterinary Medicine. He completed an equine medicine and surgery residency at The Ohio State University and is Board Certified in Large Animal Internal Medicine. After 20 years at the University of Tennessee College of Veterinary Medicine as Professor and Section Chief, he is currently LVMA Equine Committee Professor and Director of the Equine Health Studies Program at Louisiana State University School of Veterinary Medicine. Equine gastric ulcer syndrome (EGUS) is a condition in horses characterized by ulcers in the terminal esophagus, proximal (squamous) stomach, distal (glandular) stomach, and proximal duodenum [1]. Diagnosis of EGUS is based on history, clinical signs, endoscopic examination, and response to treatment. All ages and breeds of horses are susceptible to EGUS, and current pharmacologic strategies focus on blocking gastric acid secretion and increasing stomach ph, which creates a permissive environment for ulcer healing. However, long-term treatment with pharmacologic agents is expensive and requires frequent daily handling of the horse. Recently, nutritional and dietary management factors have been identified to play an important role in gastric ulcers in horses. Thus, diet and nutritional management can be employed as an adjunct and follow-up to pharmacologic therapy to decrease ulcer severity and recurrence. This review focuses on nutritional and dietary factors that have been implicated to cause EGUS and how the horse diet can be managed to lessen ulcer severity and prevent recurrence of EGUS. Highlighted in this review are the basic anatomy and physiology of the equine stomach, current feed management practices that put the horse at risk for EGUS, and dietary strategies that can decrease ulcer severity and prevent recurrence once ulcers are successfully treated. Anatomy and gastric acid secretion Horses are predisposed to gastric ulcers because of their compound stomach. The majority (80%) of ulcers occur in the proximal-third of the stomach, which is lined by non-glandular 1 / 6

2 stratified squamous epithelia. The distal two-thirds of the stomach are lined by glandular mucosa that secrete protective mucus and bicarbonate, as well as hydrochloric acid (HCl), and pepsinogen for digestion [2]. This glandular region also has an extensive capillary network and undergoes rapid restitution of epithelium when injured. Approximately 20% of ulcers occur in this region, and many heal rapidly without therapeutic intervention. The nonglandular squamous mucosa is predisposed to acid injury because it lacks this substantial protective mucus and bicarbonate layer [3]. Horses are continuous gastric HCl secretors, and acid exposure is thought to be the primary cause of EGUS [4]. Gastric acid secretion is stimulated by gastrin, histamine, and acetylcholine from the Vagus nerve. However, other acids (volatile fatty acids [VFA], bile acids [BA], and lactic acid [LA]) and enzymes (pepsin) found in the stomach also contribute to an acidic environment and low stomach ph. A recent study found that horses have a lower ph in the proximal stomach during early morning (1:00 to 9:00 AM), which suggests a circadian pattern for gastric acid secretion [5]. Prolonged exposure of the proximal stomach to a low ph environment is the likely cause of EGUS and is similar to gastroesophageal reflux disease (GERD) in humans. Synergistic action between VFA, LA, BA, and HCl may cause acid damage to the non-glandular mucosa of the stomach, leading to EGUS [6, 7, 8]. Both HCl alone and in combination with VFA (ph 4.0) byproducts of grain fermentation by resident stomach bacteria have been shown to inhibit non-glandular stomach mucosal cell sodium transport, resulting in cell swelling and eventual ulceration. The ulcerogenic effects of VFAs were dose-dependent, and the severity of the damage was related to VFA carbon chain length [7, 8, 9]. However, a recent study showed that D- and L- lactic acids, also byproducts of bacterial fermentation of grain, when exposed to the non-glandular stomach mucosa in vitro in an acid environment, did not significantly alter barrier function or sodium transport through the tissues, when compared to VFA with similar PKa [10]. Thus, the role of LA in the cause of EGUS needs further investigation. Bile acids, on the other hand, were shown to increase non-glandular mucosal cell permeability to hydrogen ions, which eventually leads to ulceration [6]. However, the effects of BA in EGUS are questionable because they usually come from less acidic duodenal reflux and are non-ulcergenic at a ph >4 [11]. Also, the proteolytic enzyme pepsinogen, which is cleaved to pepsin at a ph 2 g/kg body weight (BW) of starch per day were likely to have a 2-fold increase in gastric ulcer severity score of 2. Although the absolute fiber and grain requirements have not been determined for horses, current recommended levels of long-stem, high quality forage are at kg per 100kg of BW and 0.5 kg per 100 kg BW concentrates [9, 48]. Straw should not be fed as a sole source of forage! 2 / 6

3 Decrease size and increase frequency of concentrate feeding Serum gastrin concentrations are high in horses fed high concentrate diets [45]. Gastrin is the only hormone known to stimulate secretion of hydrochloric acid, and rations that contain more readily available nutrients, such as pellets and sweet feed, produce a significant increase in postpranial gastrin concentrations. In particular, grain feeding was shown to delay gastrin secretion, which corresponded to an increase in gastric acid secretion after the stomach had emptied the grain contents [49]. Also, high concentrate diets are high in hydrolysable or water soluble carbohydrates. Hydrolysable carbohydrates are readily fermented by resident stomach bacteria, resulting in the production of VFAs, which, in the presence of a low stomach ph ( 4), cause damage to the NG squamous mucosa [7-9, 22]. The size of the grain meal may also affect the extent of intragastric fermentation, thereby affecting VFA production [50]. Métayer et al. compared the gastric emptying rates in horses fed a small (300g/100 BW) vs. large (700g/100 BW) high starch concentrate. Although the calculated rate of gastric emptying (g/min) was higher with the large meal, gastric emptying in terms of percent of the original meal was much slower. Therefore, when horses are fed large, starch rich meals, intragastric fermentation and VFA fermentation may be favored because of the large amount of fermentable carbohydrates and the longer retention time within the stomach. In the same study, when comparing the high and low starch meals, gastric emptying was significantly faster for horses consuming a meal lower in starch than one high in starch. Larger meal size and higher starch content were associated with gastric emptying in terms of percent of total original meal. A recent study showed that when grain was fed at 0.5 kg/100 kg BW, VFA concentrations were below threshold values for causing damage to nonglandular mucosa [9]. Thus, grain or concentrates should not be fed in excess of 0.5 kg/100 kg BW every 6 hours. Antibiotics vs. probiotics Helicobacter pylori and other Helicobacter species have not been shown to cause EGUS, although Helicobacter DNA has been isolated from the glandular and non-glandular stomach mucosa in horses [51,52]. Instead, other resident, acid-tolerant bacteria (E. coli, Lactobacillus, and Streptococcus) are suspected contributors to EGUS, and a large population of these bacteria was isolated from the gastric contents of horses fed various diets in one study [53]. In rats, which have a compound stomach similar to horses, bacteria (E. Coli) rapidly colonized acetic acid-induced stomach ulcers and impaired ulcer healing [54]. In this study, oral antibiotic treatment with streptomycin and/or penicillin suppressed bacterial colonization of the ulcer and markedly accelerated ulcer healing compared to placebo-treated controls. Also, oral administration of lactulose resulted in increases Lactobacillus growth and colonization of the ulcer bed. In a recent study in horses with spontaneously occuring gastric ulcers, an antibiotic 3 / 6

4 (trimethoprim suphadimidine) or a probiotic preparation containing Lactobacillus agilis, L. salivarius, L. equi, Streptococcus equinus, and S. bovis administered orally decreased ulcer number and severity compared to untreated controls [55]. These data suggest that resident stomach bacteria are important in maintenance and progression of non-glandular gastric ulcers in horses. Treatment with antibiotic and/or probiotic preparations may facilitate ulcer healing after 2 weeks of treatment, with the full effect occuring after 4 weeks of treatment. Thus, antibiotic treatment may be indicated in horses with chronic non-responsive gastric ulcers, but more importantly, probiotic preparations containing Lactobacillus and Streptococcus may be helpful in prevention of gastric ulcers or may be used as an adjunct to pharmacologic treatment. Dietary supplements A plethora of dietary supplements on the market for horses boast efficacy in treatment and prevention of gastric ulcers. However, many of these products have not been tested in the horse, and to date, very little scientific evidence exists on their efficacy. Below are several supplements that have some scientific testing or have ingredients that have been shown to be helpful in ulcer treatment and prevention. Seabuckthorn berry extract There is an increasing interest in the use of herbs and berries that may have therapeutic application in humans and animals. Berries and pulp from the seabuckthorn plant (Hippophae rhamnoides) are high in vitamins, trace minerals, amino acids, antioxidants and other bioactive substances and have been used successfully to treat mucosal injury, including decubital ulcers, burns and stomach and duodenal ulcers in humans [56, 57]. In addition, seabuckthorn berries have been shown to successfully treat and prevent acetic acid-induced gastric ulcers in rats [58]. A recent study was completed to evaluate the efficacy of seabuckthorn berry pulp and extract (3 ounces fed twice daily; SeaBuck Complete, Seabuck, LLC, Midvale, UT) on the treatment and prevention of gastric ulcers in horses [59]. This preparation of seabuckthorn berries did not significantly decrease non-glandular gastric ulcer scores in eight treated horses, compared to the untreated controls; however, this preparation prevented an increase in gastric ulcer scores following an alternating feed deprivation, ulcer induction model, compared to untreated control horses, which had a significant increase in gastric ulcer scores. Also, gastric ulcer scores in seven of the eight seabuckthorn berry-treated horses either stayed the same or decreased compared to just two of the eight untreated controls. Although this preparation of seabuckthorn berry did not heal ulcers in these horses, it may be efficacious in the prevention or worsening of non-glandular gastric ulcers in horses during times of stress. EGUSIN 250 (Pellet) and SLH (Powder) EGUSIN (Centaur, Inc., Kansas City, KS, USA) is a dietary supplement which contains two antacids (immediate and long acting), lecithin (phospholipid), and pectin, as well as micro-milled whole oats (groats), which contains Beta-glucan-gels, insoluble oats fibers, polar lipids and 4 / 6

5 natural antioxidants. These ingredients help protect the stomach from the damaging effects of stomach acid and against generation of oxygen free radicals. In a study performed at LSU, EGUSIN fed horses had fewer and less severe ulcers after 5 weeks of feeding when compared to untreated controls. There was no alteration in blood ph in horses in this study and stomach ph remained low and did not change significantly over the treatment periods. Calcium carbonate supplements (Neigh-Lox) Many supplements on the market contain calcium carbonate, a primary component of human antacid preparations (Tums; Rolaids). These products contain varying concentrations of calcium carbonate and various other herbs and coating agents. The author (FMA) performed a small study with an antacid preparation containing calcium carbonate (Neigh-Lox, Kentucky Performance Products, Versailles, KY) to determine efficacy in treatment and prevention of gastric ulcers in horses (Frank M. Andrews, DVM, MS, Knoxville, TN, unpublished data, 2001). In that study, four healthy horses were fed hay and a small amount of grain top-dressed with 4 ounces of this calcium carbonate supplement twice daily for 3 weeks. There was no significant difference in gastric ulcer scores between control horses and treated horses; however, gastric juice ph remained 4 for 2 hours after feeding, when compared to control horses. Also, in an in vitro study, this supplement, when added to acid damaged stomach tissue, resulted in recovery of sodium transport. Thus, these data suggest that calcium carbonate preparations may have some efficacy in maintaining mucosal integrity, but may need to be fed more frequently than twice daily to prevent EGUS. Oils (corn oil, rice bran oil) Dietary fats delay gastric emptying time in humans and other species [60]. In contrast to most species, gastric emptying rates are slower in horses fed a high carbohydrate diet, compared to horses fed a high fat diet, although these rates were not statistically significant [61]. However, gastric relaxation was significantly greater in horses fed the high carbohydrate diet compared to horses fed the high fat diet. Supplementation of dietary fat may not have a profound effect on gastric emptying in horses. However, in another study [62], ponies fed dietary corn oil (45 ml, orally, once daily) by dose syringe with gastric cannulas had a significantly lower gastric acid output and increased prostaglandin concentration in gastric juice. The authors conclude that corn oil supplementation could be an economical approach to the therapeutic and prophylactic management of glandular ulcers in horses, especially those associated with the use of non-steroidal antiinflammatory drugs. In contrast to the previous study, results from an evaluation of the anti-ulcerogenic properties of corn oil, refined rice bran oil and crude rice bran oil showed no statistical differences in non-glandular ulcer scores between the treatment groups [63]. However, glandular ulcers were rare in these horses. Horses were fed the oil (8 ounces, once daily, mixed in grain) for 6 weeks. In this model, dietary oils did not prevent non-glandular gastric ulcers in these horses, suggesting that dietary oils may not be useful in treatment or prevention of non-glandular ulcers, but may be helpful in treatment or prevention of glandular ulcers. 5 / 6

6 Concentrated electrolyte pastes or solutions Repeated oral administration of hypertonic replacement electrolyte solutions, commonly given to endurance horses, has been shown to increase the number and severity of gastric ulcers [43]. Thus, these products should be used with caution in horses and may be best given after exercise with feed to minimize their effects on the gastric mucosa. Conclusion 1. If gastric ulcers are diagnosed by your veterinarian, then initiate effective pharmacologic treatment (GastroGard or Ranitidine) to heal the ulcers. 2. Provide a minimum of 1 to 1.5 kg/100 kg BW of long stem, high quality forage free-choice throughout the day and night. 3. Feed alfalfa hay or a mixture of alfalfa hay to help buffer stomach acid. 4. Feed grain and concentrates sparingly. Give no more than 0.5 kg/100 kg BW of grain or grain mixes (such as sweet feed), and do not feed grain meals less than 6 hours apart. Weigh all grains before giving. 5. Try corn oil or other tested dietary supplements (Seabuckthorn berry, EGUSIN 250 or SLH, or Zinpro performance minerals) to prevent recurrence of ulcers 6. Fee hypertonic electrolyte pastes or supplements after exercise mixed with a small amount of grain (see 4 above). 7. Consider therapeutic or preventative doses of effective pharmacologic agents (GastroGard or Ranitidine) in horses that are performing high intensity exercise, traveling, or in a high-stress situation. References Upon Request ( fandrews@lsu.edu ) 6 / 6