If your dog is struggling with SID (small intestinal dysbiosis) or bile or acid reflux, you might want to try a little Slippery Elm powder to alleviate the problem before trying chemical based antibiotics or acid reflux medicines.
Slippery Elm (SE) is a natural powder made from the inner bark of the American Elm Tree. It is also know as Ulmus Rubra. It is a known mucilage with beneficial prebiotic properties and has been used by dogs, cats and people to address gastrointestinal distress with no known adverse effects, unless there is an Elm Tree allergy.
Slippery Elm Powder (SE) can be purchased at most health food stores or ordered online in loose bulk packages or loose in bottles.
The 2017 revised suggested dosing instructions for dogs and cats is as follows (or in many cases even less SE works as well or better in many cases):
Give Slippery Elm (SE) powder with breakfast and dinner meals. It can also be given separately with something like yogurt. Just be sure to always give with moisten food, and add a spoon or two of water as SE is a mucilage and will thicken. Incubating not necessary. SE can be give for just a few days, or a week or two…. or it may be given at a reduced amount continuously as a maintenance supplement. Remember…. sometimes even less (Slippery Elm) works better…..
1/8 tsp for dogs under 10lbs,
¼ tsp for dogs 10lbs to 30lbs,
½ tsp for dogs 30lbs to 80lbs,
3/4 tsp for dogs 80lbs to 100lbs,
1 tsp for dog 100/+lbs.
Slippery Elm chemical scientific analysis
Some structural features of the mucilage from the bark of Ulmus fulva (slippery elm mucilage)
Slippery elm mucilage contains residues of l-rhamnose, d-galactose, 3-O-methyl-d-galactose, and d-galacturonic acid. The methylated polysaccharide yields 3-O- and 4-O-methyl-l-rhamnose, 2,3,4,6-tetra- and 2,3,6-tri-O-methyl-d-galactose, and 2,3,4-tri- and 2,3-di-O-methyl-d-galacturonic acid, in addition to trace amounts of 2,3,4-tri and 3,4-di-O-methyl-l-rhamnose and 2,4,6-tri-O-methyl-d-galactose. Borohydride reduction of the periodate-oxidised polysaccharide yields a polyalcohol, which, on partial hydrolysis with acid, affords O-(3-O-methyl-d-galactopyranosyl)-(1 → 4)-O-(3-O-methyl-d-galactopyranosyl)-(1 → 4)-O-(3-O-methyl-d-galactopyranosyl)-(1 → 4)-l-rhamnose. Mild, acid hydrolysis yields a Smith-degraded polysaccharide. Methylation analyses are reported for the polyalcohol and for the Smith-degraded polysaccharide. It is concluded that the polysaccharide contains chains of 3-O-methyl-d-galactose residues attached to the C-4 positions of certain l-rhamnose residues, and that 3-O-methyl-d-galactose residues occur in some cases as non-reducing end-groups. d-Galactose is attached as single residues or as 4-O-substituted residues to the C-3 positions of some l-rhamnose residues. This evidence indicates that the polysaccharide is more highly branched than was at one time supposed.
- J. POLYMER X I . : PART C NO. 36, PP. 461-466 (1971)
- Structure of Slippery Elm Mucilage (Ulmus Fulva)
- R. J. BEVERIDGE, J. K. N. JONES, R. W. LOWE, and W. A. SZAREK Departmefit of Chemistry, Queen ‘s University, Kingston, Ontario, Canada SYNOPSIS The structure of the mucilage has been investigated using (a) the methylation p r e cedure, (b) by oxidation of the polysaccharide with periodate (the Smith procedure), and (c) by its partial hydrolysis or methanolysis with the formation of sugars and ol& gosaccharides. It is composed of a main chain of alternating g-galacturonic acid and &- rhamnopyranose residues joined by &linkages through positions 4 of the galacturonic acid and 2 of the &-rhamnopyranose. The polysaccharide has side chains, containing one or two residues of 3-Q-methyl-~-galactopyranose or a-galactopyranose, attached to some &- rhamnose residues a t C-4 and C-3, respectively. The synthesis of the disaccharide present at a branching point, namely, Q-(3-Q-methyl-~~-galactopyranosyl)-(l~)-~-rhamnose – is described. INTRODUCTION Anderson [ l ] , who was a pioneer in the analysis of gums and mucilages, examined the mucilage obtained from the bark of the slippery elm tree (Ulmus &ha) in 1934. He showed that it contained B-galacturonic acid,&alactose and – L-rhamnose residues, and that a residue, relatively resistant to acidic hydrolysis, was composed of Dgalacturonic acid and L-rhamnose. He also observed that, on acidic hydrolysis o f the mucilage, l o s s of viscosity of the solution was accompanied by the formation of an insoluble residue termed X-body. In 1939, it was shown [ 2 ] that, in the fraction resistant to acidic hydrolysis, the _P galacturonic acid component was joined to an L-rhamnose residue through the hydroxyl group at C-2 of the I,-rhamnose portion by an a-glycosidic linkage. Methylation of the polymer wasdifficult to achieve by the Haworth procedure  , and it was found more convenient to convert the polymer into its thallium derivative  which, on heating in methyl iodide, gave the methylated polymer. The composition of this polymer was determined, after methanolysis, by fractional distillation of the glycosides, the separation being followed by change of boiling point, refractive index, and optical rotation of the fractions. Each fraction was hydrolyzed and examined. Identification of the components was made by converting them into known crystalline compounds. Despite the 46 1 0 1 9 7 1 by John Wiley & Sons, Inc.
- 462 BEVERIDGE ET AL. uncertainties inherent in this tedious procedure, results were obtained [ 51 which were later [6, 71, for the most part, substantiated by modern methods of analysis. Anderson [ I ] in his earlier work had commented on the presence of methoxyl groups in slippery elm mucilage. With the advent of paper chro- matography it was possible to re-examine the sugars produced on hydrolysis of the polymer. This led to the isolation and identification of 3-Q-methyl- – Dgalactose  , the first time a methylated sugar had been found as a component of a naturally occurring polysaccharide. The isolation of this sugar required re-examination of the products produced on hydrolysis of the methylated polymer, because 3-Q-methyl-D-galactose could yield, on further methylation, 2,3,6-tri- or 2,3,4,6-tetra-Q-m~hyl-D-galactose, – both of which had been detected earlier [ 5 ] . RESULTS Periodate Oxidation and Methylation Analysis of the Mucilage 3-Q-Methyl-Q-galactopyranosides are unaffected by the periodate reagent while _D-galactosides containing hydroxyl groups on adjacent carbon atoms are oxidized. It was argued, therefore, that oxidation of the polysaccharide by periodate, followed by reduction (NaBH,) of the product and a further hydrolysis, should yield fragments enriched in 3-Q-methyl-D-galactose. As ex- pected from the results of methylation analysis, R-galactoseand R-galacturonic acid were practically completely destroyed after this treatment, but L-rhamnose and 3-Q-methyl-Q-galactose were present in relatively large amounts. Moreover, methylation analysis of the polymer, after periodate oxidation, reduction, and then methylation, led to the isolation of 2,3,6-tri- and 2,3,4,6-tetra-Q-methyl- – – D-galactose, indicating the possibility that chain(s) of 3-Q-methyl-D-galactose might be present in the original polysaccharide . This was substantiated when three oligosaccharides were isolated  , after graded hydrolysis with hot dilute acid of the oxidized and reduced mucilage. These were identified as Q(3-Q-methyl-~-~-galactopyranosyl)-( 1 +4)-krhamnose ( I ) , Q- (3-Q-methyl-~-~-galactopyranos~~1~4)-3-~-methyl-~-galactose (2), and 0- (3-Q-methyl-fl-D-galac topyranosy l)-( 1 +4)-0_(3-Q-me th~l-P-&ylactopyranosyl-( 1 +4)-LrhamnoG (3), by chemical and nuclear magnetic resonance (nmr) studies  , Disaccharide 1, on hydrolysis, yielded 3-Q-methyl-D-galactose – and – – Lrhamnose in a molar ratio of 1 : 1 as determined by paper chromatographc and gas-liquid chromatographic (glc) techniques. On reduction and hydrolysis, 3-0- methyl-g-galactose and &-rhamnitol were produced, showing that the rhamnoG was the reducing portion of the disaccharide. Methylation of the disaccharide, followed by methanolysis of the product, yielded 2,3,4,6-tetra-Q- methyl-g-galactose and 2,3-di-Q-methyl-Grhamnose identified by glc. Similarly, the reducing disaccharide 2 gave 3-Q-rnet~ylyl-~-galactose only, on hydrolysis, and after methylation and hydrolysis, it yixded 2,3,4,6-tetra- and 2,3,6-tri- – O-methyl-Qgalactose in a ratio of approximately 1 : 1, determined quantitatively by glc. %saccharide 3, on hydrolysis, gave 3-Q-methyl-D_-galactose – and
- STRUCTURE OF MUCILAGE 463 – – Lrhamnose in a ratio of 2:1, and, on hydrolysis after reduction (NaBH,) rhamnitol was produced, showing that L-rhamnose was at the reducing end of the trisaccharide 3. Methylation of thetrisaccharide, followed by hydrolysis, yielded 2,3,4,6-tetra- and 2,3,6-tri-Q-methyl-~-galactose and 2,3-di-Qmethyl-_L rhamnose, the identities of which were confirmed by comparison with authentic specimens (glc). Disaccharide 2 and trisaccharide 3, when examined in deuterium oxide solution, showed a doublet at 7 8.58, in the nmr spectrum, assigned to the C-methyl group of the L-rhamnose residue. Disaccharide 2 showed a methoxyl signal at 7 6.39, while% the spectrum of the trisaccharide 3 two methoxyl signals at 7 6.38 and 6.30 were detected. These two signals were also observed in the spectrum of 2 , when it was examined in deuterium oxide solution. The formulation of 2 as _0-(3-Q-methyl-@-galactopyranosyl)-( 1-+4)& rhamnose was corroborated by comparison of the naturally derived product with a sample obtained by a structurally definitive synthesis. Earlier work  on the analysis of the methylated mucilage had indicated the presence of 2,4,6-tri-Q-methyl-~-galactose. This was probably detected because it readily forms a well crystalline N-phenylglycosylamine derivative, and is, therefore, easily detected even when small quantities only are present. More recent work  has indicated that this material is present in small amount in the hydrolyzed methylated polymer, and is probably an artifact resulting from in- complete methylation of the polysaccharide. Table I shows the relative amounts
- 464 BEVERIDGE ET AL. of methylated sugars produced. As a result of these figures and bearing in mind that the structure of the aldobiouronic acid component is known, one of many possible structures for the mucilage is shown in Figure 1. TABLE I Examination of Methanolysis and Hydrolysis Products from Methylated Polysaccharide – O->Iethyl sugars Approx. relative proportions molar 2,3,4-Tri-c-methyl-~-rhamnose Trace 3,4-Di-~-methyl-L-rhamnose – Trace 3-c-Methy l-L-rhamnose – +/2 4-2-Me thy 1 -L-rhamnose ++ 2,3,4,6-Tetra-c-methyl-~-galactose – +++ 2.3,6-Tri-~-methyl-~-galactose +++ – 2,4,6-Tri-~-methyl-D-~alactose – 2,3,4-Tri-~-methyl-~-galacturonic acid 2,3-Di-~-methyl-~-galacturonic acid Trace +/2 ++ 4 t I 3 -0tvie-D-Galp – – 4 t I 3-OMe-D-Galp – – – FIG. 1. A possible structural fragment for the water-soluble polysaccharide obtained from slippery elm mucilage.
- STRUCTURE OF MUCILAGE 465 Methanolysis of the Mucilage Link and his associates , in their examination of the structure of pectin, showed that the polymer could be degraded by boiling methanolic hydrogen chloride. They were able to obtain an insoluble polymeric residue, resistant t o further hydrolysis, which was composed of Q-galacturonic acid residues as their methyl esters. Inspection of the structureproposed above for slippery elm mucilage indicates that the polymer might fragment, on methanolysis, at the 1+4 linkage between L-rhamnose and D-galacturonic acid to yield oligo- saccharides containing tfiree to four sugz residues. Surprisingly, on meth- anolysis, the mucilage is converted into methyl glycosides of Pgalactose and 3-Q-methyl-~-galactose, and an insoluble portion, resistant to methanolysis, which contazs only Q-galacturonic acid (48%, calculated as C, H, O,-COOCH,) and krhamnose which were detected, after acid hydrolysis, by paper chro- matography. The nmr spectrum of the methanol-insoluble portion indicated the presence of as-methyl residue at 7 8.65 and an ester methoxyl group at 7 6.1 0 in the approximate ratio of 1 : l . Gel chromatography of this material on Sephadex G50 indicated that the material had a molecular weight of 8,000-9,000 [lo]. The optical rotation in water (t93″) suggested that most of the &-rhamnopyranose residues were a-linked to the L&alacturonic acid groups which were in turn a-linked to the L-rhamnopyranose – residues. On reduction (sodium borohydride and boric acid) only some of the galacturonic acid residues were converted into galactose which was detected by paper chromatography after hydrolysis by acid of the partly reduced polymer. The polysaccharide was, therefore, methylated by the Kuhn procedure [11 J , reduced (LiAlH,), and then remethylated. Acid hydrolysis of this material, followed by reduction with sodium borohydride, acetylation, and glc of the derived acetates, showed the presence of 3,4-di-O-methyl-_Grhamnitol and 2,3,6-tri-Q-methyl-Q-galactitol in the approximate ratio of 1 : l r t h e presence of no monomethyl rGmnitol was detected. These results are consistent with the structural formulation for slippery elm mucilage shown in Figure 1 . Synthesis of Disaccharide 1 Disaccharide 1 was synthesized  from 2,4,6-tri-Q-acetyl-3-Q-methyl- a-ggalactosyl chloride (4) and benzyl 2,3-Q-isopropylidene-a-~-rhamonpyran- oside (5) as shown in Figure 2. De-Q-acetylation of th; condensation product of 4 and 5 , followed by acid hydrolysis under mild conditions to remove the isopropylidene residue, gave the benzyl glycoside of I which, on hydrogenolysis, yielded 1, identical in all respects with the product isolated from the mucilate . Acknowledgment The authors thank the National Research Council of Canada for the award of a scholar- ship (to R. J. B.) and for a grant which made this work possible.
- 466 BEVERIDGE ET AL. ââQC, + H o w P h OAC c I I C 0, P A 0 v2ph OAc 0 0 â r â 1 FIG. 2. Synthesis of _O-(3-Q-methyl-~Q-galactopyranosyl)-( – 1â4)-~-rhamnose . – ( I ). REFERENCES 1. E. Anderson,J. Biol. Chem., 104, 163 (1934). 2. R. E. Gill, E. L. Hirst, and J. K. N. Jones,J. Chem. SOC., 1469 (1939). 3. W. N. Haworth,J. Chem. Soc., 107,8 (1915). 4. C. M. Fear and R. C. Menzies,J. Chem. SOC., 937 (1926). 5 . R. E. Gill, E. L. Hirst, and J. K. N. Jones,J. Chem. SOC., 1025 (1946). 6. R. J . Beveridge, J. F. Stoddart, W. A. Szarek, and J. K. N. Jones, Gzrbohyd. Rex, 9, 7. R. J. Beveridge, W. A. Szarek, and J. K. N. Jones, Curbohyd. Rex, 19, 107 (1971). 8. E. L. Hirst, L. Hough, and J. K. N. Jones, Nature, 165, 34 (195O);J. Chem. Soc., 323 9. S. Morell, L. Baur, and K. P. Link, J. Biol. Chern, 105, 1 (1934). 10. S. C. Churms and A. M. Stephen, Curbohyd. Rex, 15, 11 (1970). 11. R. Kuhn, H. Trischmann, and I. Low,Angew Chem., 67,32 (1955). 429 (1969). (1951).
March 2018 – Herbal Study: Slippery Elm (Ulmus Rubra) Study (people) Benefits of SE as a Prebiotic for Gastrointestinal Issues
The following is research on the success of using Slippery Elm in dogs and cats:
Expedited Management of Canine and Feline Vomiting and Diarrhea. Observational Study in 3952 Dogs and 2248 Cats Using Sucralfate-Like Potency-Enhanced Polyanionic Phyto-Saccharide—Elm Mucilage
Vol. 3 No. 3 (2013) , Article ID: 34284 , 7 pages DOI:10.4236/ojvm.2013.33036
Expedited Management of Canine and Feline Vomiting and Diarrhea. Observational Study in 3952 Dogs and 2248 Cats Using Sucralfate-Like Potency-Enhanced Polyanionic Phyto-Saccharide—Elm Mucilage
Ricky W. McCullough
Mueller Medical International Translational Medicine Research Center, Foster, USA
Copyright © 2013 Ricky W. McCullough. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received November 30, 2012; revised January 30, 2013; accepted March 5, 2013
Keywords: Canine; Feline; Vomiting; Diarrhea; Slippery Elm; Sucralfate
A potency-enhanced polyanionic phyto-saccharide of elm mucilage (PEPPS) was prescribed by 197 small animal veterinarians in an open-labeled field trial. Clients provided informed consent to veterinarians to prescribe PEPPS to 3952 dogs and 2248 cats. A 2 day/4 dose response rate, determined by veterinarians’ consensus, provided clinical threshold for a significant clinical outcome. Data was collected through phone interviews conducted over a period of 3.5 years from June 2003 through December 2006. 82% of 1928 vomiting dogs and 77% of 1064 vomiting cats responded to PEPPS within 2 days or four doses. 93% of 2024 dogs and 79% of 1184 cats with diarrhea responded to PEPPS within 2 days or four doses. PEPPS appears useful for managing vomiting and diarrhea in dogs and cats. However, a randomized blinded placebo controlled trial is needed to quantify true clinical efficacy.
Timely management of disruptive gastrointestinal (GI) symptoms poses a challenge to both veterinary and medical physcians alike [1,2]. Restoration of normal GI function requires effective means to mitigate nausea, vomiting, diarrhea, in dogs and cats  as well as colicky pain and ulcerations in horses . Current approaches in managing nausea (usually observed as inappetence), vomiting and diarrhea in small animals involve supportive care, bowel rest, pancreatic enzyme supplementation and/or appropriate anti-microbials . Management of mucosal erosions and ulceration in small companion animals centers on control of acidity, either by neutralization with antacids, reduction with histamine-2 blockers (e.g., ranitidine, cimetidine, famotidine) or inhibition with proton pump inhibitors (e.g., omeprazole, lanzoprazole, raberazole). A simplified approach in managing disparate GI symptoms would be useful for clinical veterinary practice were it safe, efficient and minimally burdensome [3,4].
The scale of the problem is significant. According to American Medical Veterinary Association  there are 150 – 197 million annual visits to small animal veterinarians in the US. Lund et al.  reported that in the US, 8.3% of veterinarian visits are for unexplained vomiting and diarrhea in dogs and cats. This translates into 12 to 16 million dog and cat visits (Appendix A) that involve diagnostic workups and treatment plans for vomiting and diarrhea. This volume however only reflects the owners who actively utilize veterinarian services. A recent survey of dog and cat owners  revealed that 40% of owners reported pet vomiting, diarrhea, inappetence and bloating yet only 17% of dog owners and 20% of cat owners actually consult a veterinarian. The survey implies that the estimated number of annual visits represents an undersized minority of animals that are actually affected. Given such a pervasive problem, any therapeutic intervention that improves management of disruptive GI symptoms would be a positive development.
Veterinary use of phyto-mucilages, particularly slippery elm, for gastrointestinal have been suggested by some [8,9]. A potency-enhanced version of elm USP, requiring less than 10% of suggested daily doses, has been prescribed by veterinarians since 2003. Veterinarians were familiar with the 2002 original formulation of canine/feline Gastrafate® which contained 5% high potency sucralfate as the active ingredient. Following successful preliminary testing  high potency sucralfate was replaced in January 2003 with magnesium chelated elm mucilage. This report presents observational data from the use of polyanionic phyto-saccharide of elm mucilage (PEPPS) in practice-based settings of small animal veterinarians.
2.1. Potency Enhanced Polyanionic Phyto-Sac Charide
Elm mucilage USP is a polyanionic phyto-saccharide . Unlike sucralfate, PEPPS contains no aluminum or sulfate. Chiefly a high molecular weight mucilage (>200,000 Daltons), it is comprised of galactose-rhamnose disaccharides. Potency-enhanced elm phyto-saccharide is prepared by suspending elm mucilage in an anion-cation solution similar to that used to formulate high potency sucralfate (HPS) . The resultant potency-enhanced phyto-saccharide (PEPPS) is muco-specific and capable of attaining augmented surface concentration of slippery elm. With sucralfate, potency enhancement ranges from 7 – 23 fold 3 hours post-administration, having a lower fold increase on normal GI lining and higher fold increase on inflamed or injured mucosa. The exact postadministration surface concentration of PEPPS is unknown. However, with PEPPS the concentration of elm USP administered is less than 8% the slippery elm dose recommended by holistic veterinarians [8,9]. The formulation strength of Elm USP in PEPPS for small animals is 0.9%. Administration of PEPPS was in accordance to weight. On average dogs or cats weighing less than 25 lbs received daily doses upwards of 72 mg, (b) animals between 25 – 50 lbs received 85 mg and (c) over 50 lbs received 120 mg.
2.2. Dosing Administration
Participating veterinarians prescribed PEPPS in accordance to weight-dose chart in label instructions. PEPPS was given twice daily with food for the majority of the patients. In the cases where vomiting and diarrhea disrupted eating and require intravenous hydration, PEPPS was given orally without food.
3.1. Study Design—Observational Trial
This study was an open labeled non-blinded observational trial. Information was collected regarding (a) weight of the dog or cat and (b) the nature and length of their GI symptoms at time of adding PEPPS. The length of illness is not reported.
As an observational study, treatment intervention was not randomized. By design, differences in outcomes are observed without regard to similarities or dissimilarities of patient characteristics prior to treatment. In fact, in this type of study, treatment decisions were made by veterinarians prior to use of PEPPS, the selection of PEPPS being made by the veterinarian due to concern that prePEPPS treatments were ineffectual. In this trial the question addressed is not one of the efficacy of PEPPS. Instead the question addressed is one of the relative merits of PEPPS as a competing treatment or intervention. Outcome of merit is relative to the expectation of the participating veterinarians. As discussed below a clinical response of 2 days or 4 doses merited note to the veterinarians involved. This study reports the percentage of dogs and cats with vomiting and diarrhea who responded to PEPPS while on failing therapies.
3.2. Comparative Control
As an observational study, there were no control groups. To provide a comparative “control” experience, each veterinarian was asked to reflect on their respective experience and select from a choice of a clinical response times which they would deem to deviate significantly from the expectations of their clinical experience. Most of the small animal veterinarians (85%) felt that a clinical response of 2 days or 4 doses would mark a significant departure from their clinical expectations and this was based on their experience managing vomiting and diarrhea in dogs and cats. This consensus of significant departure from expected time of clinical response was used to benchmark the primary outcome and a meaningful response. In essence, expectations of past clinical experience (replete with interventions requiring more time to work) served as a “comparative control” albeit a subjective one.
All animals were privately owned and owners’ consent was obtained by veterinarians.
3.4. Veterinarians Participating in the Study
Veterinarians placing orders for commercially available PEPPS were recruited to participate in this open-labeled trial. Each had more than 5 years of professional practice. Veterinarians were recruited from June 2003 through December 2006. All veterinarians prescribing PEPPS were engaged exclusively in primary care of small companion animals. They were experienced in the standards of care in treating vomiting and diarrhea in dogs and cats. Out of 256 small animal veterinarians, 197 practicing in 48 states completed the study, the remainder lost to follow up due to their inability to complete the protocol. Veterinarians received no honorarium for their participation.
3.5. Sequential Participation
Participation in the study was sequential, determined solely by the order of spontaneous requests for product made by veterinarians responding to notification of product’s availability. The veterinarians were self-selected. Information prompting orders pertain to the usefulness of PEPPS in the management of vomiting and diarrhea in small animals.
3.6. Inclusion/Exclusion Criterion for Dogs and Cats
Dogs and cats were brought to the veterinarian by clients primarily due to vomiting and/or diarrhea. Included in the trial were dogs and cats with vomiting and/or diarrhea for more than 3 days with or without bleeding and dehydration. Animal’s symptoms were attributed to gastrointestinal infections from viral, bacterial and protozoan agents or to exposure to environmental toxins. Notable inclusions were animals described by veterinarians as having hemorrhagic gastroenteritis, parvovirus enterocolitis, gastritis, intestinal “flare-ups”, and pancreatic “flare-ups”. Cases of food intolerance were included. No cases of medication induced vomiting or diarrhea included. Excluded were animals requiring surgical intervention.
3.7. Test Population
Animals included dogs and cats of varied age, breeds and weights. The size of the test population was 3952 dogs wherein 1928 were vomiting-dominant and 2024 diarrhea-dominant. Vomiting-dominant and diarrhea-dominant was defined by the major concern of the client who initiated the visit. Also included were 2248 cats wherein 1064 were vomiting-dominant and 1184 were diarrheadominant. All patients were studied across multiple office-based practices. The population was also geographically diverse with input provided from 48 out 50 states of the US.
3.8. Conditions Managed
Inappetence, vomiting and diarrhea fail owners’ attempts to adjust the pets’ diet. Following evaluation by physical exam, lab tests and in some cases x-rays the clinical impressions of veterinarian covered a broad range of diagnoses that included hemorrhagic gastroenteritis, parvovirus enterocolitis, gastritis, reflux, suspected ulcer, intestinal “flare-ups”, pancreatic “flare-ups” and “stomach issues”. The severity of GI symptoms or the presence of other (non-surgical) disorders did not preclude patients’ involvement in the study. Cases of food intolerance were included. There were no cases of medication induced vomiting or diarrhea in this study. Both dogs and cats were brought to the veterinarian due to vomiting and/or diarrhea.
3.9. Existing Treatment Regimens in Dogs and Cats
Methods of management for small animals were diverse. Existing treatment regimens for dogs and cats prior to PEPPS varied widely and included antibiotics, anti-emetics, acid reducers, pancreatic enzyme supplementation, bismuth preparations, plain sucralfate and dietary changes. To these diverse regimens PEPPS was added. Veterinarians in the study opted to add PEPPS to existing regimens that had been deemed inadequate or insufficient by them. There was no PEPPS only test group.
3.10. Primary Outcome Measure in Dogs and Cats
There were two symptom-related primary outcome measures for this trial—the cessation of diarrhea and the cessation of vomiting. The cessation of these symptoms within 2 days or 4 doses of PEPPS represented a positive outcome. This veterinarian-defined response to therapy was accepted as a meaningful clinical response (as described in section on Study Design) for the management of vomiting and diarrhea in dogs and cats in this study. Clinical observations made by veterinarians were reported by phone for data collection.
The hypothesis is that a majority of animals with serious and disruptive GI symptoms (of non-surgical etiology) when given PEPPS will experience resolution of symptoms within a timeframe (or dose administration) significant and relevant to the collective historical experience of practicing veterinarians who routinely manage such symptoms. This was a timeframe was 2 days or 4 doses.
Results are based on a per protocol analysis of the data. Chi-square analyses were performed to compare percent response between weight subgroups in dogs and cats at confidence level of 95% and 99% for confidence intervals and alpha level of 0.05.
3.13. Conduct of Observational Field Tests
The study was conducted from June 2003 through December 2006. Clinical observations made by veterinaryans were reported by phone for data collection. Phone interviews were conducted with veterinarian staff to collect results of adding PEPPS to existing treatment regimens. Results were tabulated as either a positive or negative outcome.
4.1. Dogs with Vomiting and Diarrhea ….to see actual charts please go to the website link:
The were dogs grouped roughly according to five weight categories—less than 6 lbs, 6 – 14 lbs, 14.1 – 29 lbs, 29.1 – 50 lbs and greater than 50 lbs. All dogs eventually responded to PEPPS with various clinical response times extending beyond 2 days. However, Table 1 show that 82% [CI 3.9 (CL 99%)] of 1,928 dogs with vomiting responded to PEPPS within 2 days or 4 doses, while 93% [CI 1.46 (CL 99%)] of 2024 dogs with diarrhea responded to PEPPS within 2 days or 4 doses. The collective percent response to PEPPS for vomiting and diarrhea in dogs was 88%. High percent response to PEPPS in 2 days or with 4 doses was similar across all weight classes of dogs regardless of symptom (Table 2). There were no weight-based differences in the percent response in dogs to PEPPS.
4.2. Cats with Vomiting and Diarrhea to see actual charts please go to the website link:
Cats were grouped according to 3 weight categories— less than 6 lbs, 6 to 11 lbs, and greater than 11 lbs. All cats eventually responded to PEPPS with varying clinical response times that extended beyond 2 days. However, Table 3 shows that 77% [CI 3.3 (CL 99%)] of 1064 cats with vomiting responded to PEPPS within 2 days or 4 doses. Similarly 79% [CI 3.05 (CL 99%)] of 1184 cats with diarrhea responded to PEPPS within 2 days or 4 doses. The ability for PEPPS to stop diarrhea and vomiting in 2 days or with 4 doses in cats was the same across all weight classes. Table 4 shows that there were no weight-based differences in the percent response in cats to PEPPS.
5.1. General Impressions
There are limited outpatient options for the treatment of acute vomiting and diarrhea in companion animals. For the most part, evidence-based guidance is drawn largely from human clinical trials, experimental studies in dogs and cats [13,14] and the collective clinical experience of small animal practitioners. Often what is recommended (and practiced) is manipulation of diet alone or concur-Table 1. Veterinary response to PEPPS prescribed to dogs.
Table 2. Chi-Square values comparing percent treatment response in dogs by weight.
Table 3. Veterinary response to PEPPS prescribed cats.
Table 4. Chi-square values comparing percent treatment response in cats by weight.
rently with the use of medications . Few randomized placebo controlled trials exist that offer evidence sufficient support national practice guidelines.
In this study, potency-enhanced polyanionic phytosaccharide was prescribed to 3952 dogs and 2248 cats in the private practices of 197 small animal veterinarians in the US over a 3.5 year period. The data from this study showed an association between the use of PEPPS and the resolution of vomiting and diarrhea in dogs and cats whose symptoms had failed pre-existing therapies. Causality would require a randomized, blinded, placebocontrolled trial. As in must observational trials, a standard control group was not used. Instead, the study used as its “control” the historical experience of veterinarians whose prior management of vomiting and diarrhea did not include PEPPS. Vomiting and diarrhea resolved within 2 days or 4 doses in a majority of dogs (over 80%) and cats (nearly 80%) that received PEPPS. The data supported the original hypothesis that majority of dogs and cats with serious and disruptive GI symptoms when given PEPPS will have symptom resolution within a timeframe significantly less than anticipated from the private practice experiences of the veterinarians involved. In dogs and cats with vomiting and/or diarrhea for more than 3 days with or without bleeding and dehydration the animal’s symptoms were attributable to gastrointestinal infections from viral, bacterial and protozoan agents or to environmental toxins. Notable inclusions were animals described by veterinarians as having hemorrhagic gastroenteritis, parvovirus enterocolitis, gastritis, intestinal “flare-ups”, and pancreatic “flare-ups” who were on failing treatments. The majority of these animals responded to PEPPS with the cessation of symptoms between 2 to 4 days. This study does not rule out whether on not the patients would have improved otherwise. Neither does the study exclude the possibility that patients’ improvement was from other causes, such as premature disqualification of existing treatment regimens or the combination of PEPPS with existing regimens led to improvement. It does support a plausible proof of principle. The study did demonstrate that PEPPS was associated with a 2 – 4 day cessation of vomiting and diarrhea in the majority of dogs and cats that received PEPPS twice daily by direct administration or with their food.
5.2. Disadvantages of Observational Studies
There are obvious disadvantages to an observational study of this nature. Firstly, there are no traditional control groups, the lack of which precludes objective quantification of the efficacy. What is known from this study is that a large majority of the patients got better sooner than 85% of the study’s small animal veterinarians would have thought possible based on their collective past clinical experience. The historical experience of each veterinarian and their consensus of what constitute a significant deviation from that experience are subjective. Consequently, the data offers little predictive value of efficacy. The study design, at best, provides an affirmative proof-of-concept supporting the plausible utility of PEPPS in the management of disruptive GI symptoms in dogs and cats.
A second disadvantage of this study is that the manner of recruitment gives rise to bias. Practitioners were selfselected by virtue of responding to advertisements regarding a new gastrointestinal protectant which is resold at profit if the product is prescribed to a patient. Data obtained utilizing this method of recruitment is vulnerable to a self-selection bias that is profit driven. In general, an appropriately randomized, placebo-controlled blinded investigation would best quantify the efficacy of PEPPS and thereby provide a better basis on which to predict the benefit of PEPPS in managing vomiting and diarrhea.
5.3. Strengths of This Observational Study
Despite the aforementioned drawbacks due to design, there are a number of strengths that provide a significant context for the positive results reported here, results that imply positive benefits in using PEPPS to manage unexplained diarrhea or vomiting in small animals.
The first strength of this study the is the geographic diversity of state-licensed veterinarians involved. The data reflected a nationwide experience among small animal practitioners in 48 of the 50 states. The positive findings were not a coincidence of geography but rather a reflection of generalized experience.
In addition, a study involving thousands animals across 48 contiguous states imply that response to PEPPS was not likely influenced by geographic life-styles (rural versus urban settings) of ownership, diversity of breed, client-companion animal relationships or seasonality (having been conducted over 42 months). The majority of patients demonstrated a high PEPPS response regardless of these factors.
5.4. Implications of Findings
The positive results of this study have implications regarding the physical origin of symptom-states of the GI tract. PEPPS is non-systemic agent. The entirety of its clinical effects is attributed solely to a topical action in coating the mucosal lining. Physical engagement of surface elements accessible to PEPPS as it layers along the gut lining result in a therapeutic effect. Similarly, sucralfate, another agent whose therapeutic effect is limited to engagement of the mucosal lining has been shown as well to reverse nausea, vomiting and diarrhea in small animals . Thus the positive clinical effect of PEPPS and similar surface-active agents (e.g. sucralfate) to reverse symptom-states of vomiting and diarrhea in dogs and cats, imply that those symptom-states are controlled by or to some degree, significantly influenced by physical elements associated with the mucosa onto which these agents are layered. Causal links of mucosal elements to symptom-states of the GI tract has been mentioned elsewhere, in cases involving human patients suffering from functional bowel syndromes that presenting with intestinal symptoms of nausea, vomiting, diarrhea or even constipation [17,18]. The use of surface-active agents to manage symptom-states by engagement of surface elements of the mucosal raises the question as to the nature of those elements so associated. Surely those elements should be targets for the design of other therapeutic agents.
The majority of 3952 dogs and 2248 cats with vomiting and diarrhea treated with PEPPS were observed to have unexpectedly shortened clinical course unanticipated by experienced small animal veterinarians practicing in 48 out 50 states in the US. While all patients eventually responded to PEPPS, most dogs and cats with vomiting and diarrhea responded within 2 days or 4 doses. Data from this 42-month-long observational study supports the notion that PEPPS may be useful in the practice setting to manage vomiting and diarrhea of common etiologies in small companion animals. However, blinded, randomized, placebo-controlled trials are needed to assess the true efficacy of PEPPS.
Fieldwork and data collection were funded as part of Mueller Medical International LLC research on polyanionic saccharides as in-vivo surface active agents for epithelial mediated processes in animals and humans. Thanks to Jeremiah McCullough of University of Connecticut for his assistance in the preparation of this manuscript.
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Volume for office visits was calculated from data by Lund et al.  who reported that 8.3% of dog and cat visits per year for either vomiting or diarrhea. This number was multiplied by 196 million annual veterinarian visits reported in 2007 AVMA Pet ownership sourcebook, then further multiplied by 0.85 as the proportion of total small animal veterinarian visits by dogs and cats.
Additional Slippery Elm Research
The following is the entire American Herbal Pharmacopeia paper on Slippery Elm