A Pilot Study on the Clinical Effectsof Forans Nutri-Gard® for relief ofGastric Ulcers in Horses
R. van den Hoven, S. Wlaschitz, S.Leinker, C.Uray. Clinical Department of Small Animals and Horses, Clinic of InternalMedicine and Infectious Diseases, Veterinary University of Vienna, Veterinärplatz 1, A-1210 Vienna, Austria. Introduction Since 3 meter endoscopes have become routinely available for
coating of the ulcer by a polysulfated sugar such as sucralfate.
equine diagnostic purposes, equine gastrology has come to its
This substance possibly also induces the mucosal production of
full potential. Among many other clinical investigators, it was
the protective prostraglandin E2 (PGE2), which is also the main
especially Murray and his co-operators who gave equine
goal of the third therapeutic approach according to
gastrology an upsurge. It is now commonly known that gastric
Merritt (2003). Feeding corn oil also may increase mucosal
ulcers are recognised problems in thoroughbred and standard
PGE2 synthesis (Merritt, 2003). A combination of sucralfate and
bred race horses. The prevalence in horses stabled at race
H2-antagonisten is also given to horses. If this is a rational
tracks or at training yards is estimated between 66 and 90%
combination remains questionable, since in man sucralfate is
(Hammond et al. 1986, Murray 1994). Even in leisure horses the
only used to treat ulcers in the pars glandularis and in the
prevalence is about 37% (Murray et al. 1989). Most lesions in the
duodenum and not for oesophageal ulcers. Orsini (2000)
living horse can be found endoscopically in the epithelium of the
believes that this fact may be the explanation for the apparent
pars cutanea, especially near the margo plicatus. In horses kept
lack of efficacy of sucralfate in horses, since most equine ulcers
at pasture the condition is rather uncommon (Murray 1994). It is
are not located in the pars glandularis.
presumed that the squamous epithelial lining of the parscutanea of the horse stomach has a limited resistance to peptic
The bioavailability of H2-antagonists for the horse is less than
injury similar to the oesophageal mucosa of man
in man (Orsini 2000), which complicates treatment. However
(Orlando 1991). When horses are not eating, the equine gastric
proton pump inhibitors appear to pose more potential (Papoch
mucosa becomes exposed periodically to highly acidic
1993, Sangiah et al, 1989).Treatment of race and sport horses
conditions (Murray and Schusser 1993). This condition may
with drugs like omeprazole, ranitidine and cimetidine may
occur in stabled horses that are fed oats or pellets 2 or 3 times
cause problems in doping control. Recently FEI allowed
daily in combination with limited amounts of roughage. Horses
competition horses to be treated with omeprazole and
at pasture continuously fill their stomachs with food, thereby
ranitidine, but other racing and equestrian organisations still
continuously buffering the gastric acid production and gastric
prohibit the presence of any foreign substance in the body of the
ulcers will develop less likely. The term “Equine Gastric Ulcer
horse and its excreta. Apart from doping rules and side effects,
Syndrome” (EGUS) has been adopted in reference to a number
the other drawback of these pharmacological substances is
of specifically unique problems that can manifest as mucosal
erosion and ulceration within either the oesophagus, stomachor upper duodenum, or some combination thereof (Orsini,
Alternatives to buffer intragastric pH or protect the ulcers may
2000). In the majority of cases only the stomach is affected.
be pectin-lecitin based product (Pronutin®). Venner et al. (1999)
Gastric ulceration in mature horses may be suspected from
described favourable effects on ulcer healing by this product.
subjective clinical signs such as mild to severe colic, poor
Another plant based product is Nutri-Gard®. It contains a
appetite, poor body condition, dullness and attitude changes,
concentrated level of potato cell wall fibre. The product has a
poor performance and other behavioural changes (Murray et al.
very high water binding capacity with 90% absorbed in less than
1989, Orsini 2000). As could be expected from the vague clinical
one minute. Furthermore it contains lecithin, inulin, galactose,
symptoms, Murray et al (1989) reported that the correlation
between clinical signs and severity of ulceration appearsquite variable.
The purpose of this study was to investigate the protective andhealing effect on EGUS of Nutri-Gard® in competition horses.
The therapeutic strategies for ulcer healing include 3 basic
The study was an explorative clinical study using routine clinical
approaches. The first approach is to keep the intragastric pH>4,
endoscopy techniques for evaluation of treatment and did not
which can be achieved with HCl buffering compounds such as
Al/Mg hydroxide, or alternatively with histamine –2-antagonists(H2-antagonsits) such as cimetidine or ranitidine (Furr andMurray 1989). Both drugs must be given 3 times daily. There isstill doubt on the efficacy of H2-antagonsits on ulcer healing(Nieto et al. 2001). A more efficient drug, the proton pumpinhibitor omeprazole, only needs to be given once daily(MacAllister et al, 1999) and was highly effective in a large fieldtrial (Johnson et al, 2001). The second approach may be the
Materials and Methods Clinical cases and treatment Thirteen patients with clinical and/or endoscopical symptoms of
Lesions were scored immediately by the endoscopist according
gastric ulcer disease, comprising racing animals and saddle
to the practitioner’s simplified scoring system (Andrews et al,
horses, were used. The distribution of age, gender and use are
1997; Orsini, 2000) on a scale from 0 to 3 (0 -intact mucosa, can
have mild reddening and/or mild hyperkeratosis; 1 - smallsingle or multiple ulcers; 2 -big solitary or multiple ulcers; 3 –
extended, confluent ulcers with regions with deep ulceration). All observations were recorded and photographs were taken
After initial analysis, an alternative scorings system was used tosemi-quantify lesion number and severity of blinded randomised
endoscopic photographs of the abnormal gastric areas of the
cases. Two experienced endoscopists who were in ignorance of
the case information, scored the randomly ordered picturesaccording to the system (Table II) of MacAllister et al. (1997).
Table II: No./Severity score according to MacAllister et al. (1997)
At the start of the treatment, the clinical histories of the animals
were taken in order to find out if animals had been medically
treated within the last 4 weeks. Horses that had been treatedless than 4 weeks before presentation with cimetidine,
Deeper structures involved (depth Grade 1)
ranitidine or omeprazole were not included in the trial.
The horses were stabled in the facilities of the clinic of internalmedicine for about 18 hours. After endoscopy and initiation of
therapy, animal were sent home and received their regular feed
which comprised pasture hay and commercial horse pellets,
oats or muesli. Pasture hay was of moderate quality. Nutri-Gard® was mixed with the pellets and or oats. No other
medication or feed supplement was given to the horses duringthe conduct of the trial. The management of the majority of the
The data were analysed with Friedman test using SPSS 11.5 for
horses could be supervised by personnel of the clinic of internal
Windows. Kendall correlation was used for comparison of
medicine, since most of the horses were housed on yards that
were frequently visited for other reasons too. After 14 days andafter 28 days animals returned to the clinic for their second andthird gastroscopic examination. Study design The study was set up as a longitudinal self controlled study. Gastric ulcer scores before and after Nutri-Gard® treatment were compared case by case over a one month observation period. The trial was executed from December 2003 till February 2004. Procedures After over night fasting, the animals underwent gastroscopy under standing conditions in stocks. If deemed necessary, a sedative mixture of detomidine (Domosedan®) and butorphanol (Butomidor®) was administered intravenously. Results Thirteen horses entered the study. All horses underwent a first
The EGUS Scores obtained by the unblinded observers and
and a second gastroscopic examination. Two horses that were
the Severity (SC) and the Number Scores (NS) obtained by
already healed on Day 14 were allowed to omit the final
blinded endoscopist were moderately correlated (EGUS with
examination on 28 Days. One horse that had not shown
NS: r2 = 0.66 - 0.81, EGUS with SC: r2 = 0.65 - 0.81). The median
improvement by the 14-day examination did not report for its
scores and their 95%-confidence intervals are given in Table IV.
28-day examination appointment. This horse was considered asa treatment failure.
The total numbers of ulcers had decreased by treatment as wasshowed by the1.5 unit decrease in score, but this reduction in NS
A treatment effect was already seen after 14 days of
was not statistically significant (p=0.128). The ulcers had
supplementing the feed with Nutri-Gard® in 38% (5 out of 13) of
decreased in severity in the opinion of unblinded endoscopists.
the cases. At 28 days after start of treatment the success rate
The SC had improved by 1.5 units, but this difference was also
had increased to 69% (8 out of 13). The body weight changes are
statistically not significant (p=0,203). Discussion The trial was set up as a self-controlled study. This design type is
Table III. Mean, minimum, maximum and standard deviation
suitable for initial investigations of new treatments
of body weight and ulcer score before (day 0), after 14 days
(Louis et al, 1986). We performed this study to get an impression
of treatment (day 14) and at 28 days of treatment (day 28).
whether its worth to further study the effects of the product. The
first ulcer scoring system that was used by the endoscopists
during the examination of the horses was the practitioner’s
simplified scoring system (Andrews et al, 1997; Orsini 2000), alsoknown as EGUS score. Andrews et al (1997) used this scoring
system to evaluate the effects of omeprazole treatment in a dose
confirmation trial. Using the EGUS score, we could show that
Nutri-Gard® improved or healed gastric ulcers in 69% of thetreated horses. Although 39% of the horses already showed
improvement after 14 days, most of the cases needed 28 days to
show a clear treatment effect. Andrews et al (1999) reported thatspontaneous improvement or healing of ulcers was found in 32%of their cases, while treatment with 4 mg/kg omeprazole daily for
A quantification of the effect using the EGUS score was
1 month resulted in improvement or healing of 92% of the cases.
performed and the results are given in Table IV.
The average pre-treatment score in that study was 2.2, which isslightly less than the mean EGUS score of 2.4 in our study. Taking
Table IV. Median and 95%-confidence intervals for each
a spontaneous healing percentage of 32%, the observed healing of
69% in our study analysed by Chi2-test on proportional data wassignificantly different (p=0.05). Since the clinical success rate after
Nutri-Gard® treatment was significantly greater than that what
could have occurred after spontaneous improvement or healing,we concluded that Nutri-Gard® treatment has a beneficial activity
on the healing of gastric ulcer syndrome in the horse. Compared
to the omeprazole healing rate, Nutri-Gard® under our testing
conditions appeared less potent. The healing based onimprovement of scores in our study could not be proven by
statistically significant differences.
In an explorative trial, Venner et al (1999) reported ulcer healingafter a 14 day treatment period with a pectin-lecitin based
An example of the endoscopic appearance of a healed case is
product. In contrast to this, Murray and Grady (2002) could not find
a preventive effect of this pectin-lectin complex on gastricmucosal lesions in a feed deprivation model in ponies, although in2 of 8 ponies showed some protective effect could be seen. Conclusion The conclusion of our study was that we could show that Forans Nutri-Gard® was better than spontaneous healing and that clinical ulcer scores improved after a one-month treatment period, however this trend was not statistically significant. These initial findings support further studies with the product in larger
groups of horses using more advanced study designs.
The mean body weight first increased and later decreased,
however the changes were not significant (p=0.097). The EGUS
The authors would like to thank Mr. David Foran, Foran Equine
score had improved by 1 scoring unit after one month, this
Products Ltd, a division of Forans Chemicals Ltd., Dublin 10,
difference was not statistically significant (p=0.095).
Ireland, for material and financial support. References
Andrews, F.M., Sifferman, R.L., Bernard, W., Hughes, F.H., Holste, J.E.,
Sangiah,S., MacAllister, C.G., Amouzadeh,H.R. (1989) Effects of
Daurio, C.P., Alva, R.,and Cox, J.L. (1999). Efficacy of Omeprazole paste
misoprostol and omeprazole on basal gastric pH and free acid content
in the treatment and prevention of gastric ulcers in horses.
Equine vet J., Suppl., 29, 81-86.
Res Vet Sci, 47, 350-354.
Furr, M.O., Murray, M.J. (1989). Treatment of gastric ulceres in horses
Venner,.M., Lauffs, S., and Deegen, E. (1999) Treatment of gastric
with histamin type 2 receptor antagonists.
lesions in horses with pectin-lectin complex.
Equine vet J., Suppl 7, 77-79.
Equine Veterinary Journal, Suppl. 29, 91-96.
Hammond, C.J., Mason, D.K., Watkins, K.I. (1986) Gastric ulceration in mature Thoroughbred horses. Equine vet J., 18, 284-287.
Johnson, J.H., Vatistas, N., Castro, L., Fischer, T., Pipers, F.S., Maye, D. (2001). Field survey of the prevalence of gastric ulcers in racehorses and on response of treatment of affceted horses with omeprazole paste. Equine vet. Educ., 13, 221-224.
Louis, T.A., Lavori, P.W., Bailar III, P.W., and Polansky, M. (1986). Cross-over studies and self-controlled designs in clinical research in: J.C. Bailar III and F. Mosteller (eds) Medical uses of Statistics. NEJM Books,Waltham, Massachusetts, USA, pp 67-90.
MacAllister, C.G.,Andrews, F.M., Deegan, E., Ruoff, W., and S.-G. Olovson (1997) A scoring system for gastric ulcers in horses. Equine vet J., 29, 430-433.
MacAllister, C.G., Sifferman, R.L., McClure, S.R., White, N.J., Vatistas,N.J.,Holste, ,J.E., Ericsson, G.F., and Cox, J.L.(1999). Effects ofomeprazole paste on healing of spontaneous gastric ulcers in horsesand foal: a field trial. Equine vet.J Suppl. 29, 77-80.
Merrit, A. M. (2003) Equine gastric ulcer syndrome (EGUS): anti-ulcertherepy. In Proceedings of the 8th Geneva Congress of EquineMedicione and Surgery, pp 163-164.
Murray, M.J. (1994). Gastric ulcers in adult horses. Comp. cont. Educ.pract.Vet. 16, 792-794,797.
Murray, M.J., Grodinsky, C., Anderson, C.W.,Radue, P.F.,Schmidt, G.R. (1989) Gastric ulcers in the horse: a comparisson of endoscopic findings in horses with and without clinical signs. Equine vet J., Suppl. 7,68-72.
Murray, M.J., Schusser, G.F. (1993). Measurement of 24-h gastric pH using an indwelling electrode in horses unfed, fed, and treated with ranitidine. Equine vet J., Suppl. 25, 417-421.
Murray, M.J. and Grady, T.C.(2002) The effects of a pectin-lecitin complex on prevention of gastric mucosal lesions induced by feed deprivation in ponies. Equine vet J., 34,195-198.
Nieto, J.E., Spier, S.J., van Hoogmoed, L., Pipers, F.,Timmerman, B. And Snyder, J.R. (2001). Comparison of omeprazole and cimetidine in healing of gastric ulcers and prevention of recurrence in horses. Equine vet Educ. 13, 260-264.
Orlando, R.C. (1991) Oesophageal epithelial defence agianst acid injury. J.clin. Gastroenterol. 13, Suppl. 2, S1-S5.
Orsini, J. (2000). Gastric ulceration in the mature horse: a review. Equine vet Educ. 12, 24-27.
Papoch, M.G. (1993). Anti-ulcer therapy. Vet. Clin. N. Am. 202, 1465-1468.
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