2013 Superfix Gastro-G Flavonoid treatment for Equine Ulcers Equine Gastric Ulcer syndrome is common in race horses treatment is usually with Gastrogard and dietary management with antacids and supplements to promote ideal gut health. None of these provide the ideal therapy which is to provide healing and restore integrity and balance, could plant flavonoids be a better all round treatment? Dr. Carol Michael Superfix 12/3/2013 Ideal therapy for gastric ulcer syndrome in horses is to relieve the pain, heal the ulcer Effectively prevent recurrence. To date no drug or nutritional therapies fit these criteria To achieve peace and harmony in the gut there should be a balance between the aggressive action of the digestive juices (acid and pepsin) and the protective barrier of the mucosal membrane. Ulcers are caused by an imbalance in the amount of gastric acid produced or diminished mucosal barrier by; An increase in gastric acid production The bicarbonate fails to neutralise the stomach acid and/or an impaired mucous secretion Superficial lesions and granulations on the mucosal layer in the stomach and hind gut which are caused by Bute, drug or bacterial infection. Drug and nutritional therapy is aimed at prevention of gastric acid – Gastrogard- blocks the production of gastric acid by inhibiting the proton pump this remains the most effective course of treatment against ulcers caused by the over production of gastric acid but has no effect against ulcers caused by bacteria, nor inflammation nor is omeprazole able to stimulate mucus –bicarbonate flow or improve the integrity of the mucosal lining of the stomach. Cimetidine and Ranitidine- both block the action of histamine, diminishing the production of gastric acid. Antacids- either increased saliva production from feeding continuous hay or buffering and coating the stomach with added dihydroxy-aluminium sodium carbonate, aluminium phosphate and magnesium carbonate. Omeprazole is an effective treatment for gastric ulcers but synthetic drugs are not able to provide a balanced, strong or healthy gastro intestinal tract. Plants are the only therapy to give a shotgun effect, firing multiple compounds into the system to bring about a number of biological beneficial processes. There are certain plants which contain flavonoids able to target the gastrointestinal tract, treat the gastric ulcers, provide pain relief and destroy the harmful bacteria which cause hind gut colitis. Flavonoids are in essence functional foods and can be given as part of a normal diet in larger amounts to treat gastric ulcers or in a lower dose to offer protection stopping the over production of gastric acid and by encouraging a thicker mucosal membrane. Gastro G contains compounds with several natural proton pump inhibitors (PPI’s) The action of these natural PPI’s (Galactitol, Catechin, Epicatechin, Quercetin, Rutin) is highlighted in the following experiment. In this experiment gastric ulcers were induced by the use of ethanol. Ethanol destroys the mucus barrier in a similar way to the damage done by the over production of gastric acid. M.I. represents the flavonoids in Gastro G and omeprazole is the active ingredient in Gastrogard. The experiment was over 7 days and the protection offered by M.I. was better than that of the omeprazole at 55% and 70% for the full dose of M.I. (10mg/kg) Chronic gastric lesions induced by ethanol Size of Lesions 140 120 100 80 60 40 20 0 control omeprazole M.I. 3mg/kg M.I. 10mg/kg M.I. 30 mg/kg In vitro inhibition of the proton pump activity with flavonoids (M.I.) and a comparison with omeprazole IC50 = 41 µg/ml 6 5 4 3 2 IC50 = 41 µg/ml 1 0 In the second and third experiments gastric ulcers were induced by the use of indomethacin and acetic acid which prevents the production of prostaglandin. Prostaglandin has 3 jobs –the first is to limit gastric acid production and the second is to stimulate mucus- bicarbonate secretion. The third is to stimulate blood flow to the area which is an important part of pain relief in horses. Treatment of chronic gastric lesions induced by indomethacin size of lesions 40 35 30 25 20 size of lesions 15 10 5 0 control omeprazole M.I.3mg/kg M.I. 10mg/kgM.I. 30mg/kg treatment of chronic gastric lesions induced with acetic acid size of lesions 100 90 80 70 60 50 40 30 20 10 0 size of lesions control omeprazole M.I. 3mg/kg M.I. 10mg/kg M.I. 30mg/kg At the higher dose M.I. is more effective than omeprazole at treating the gastric ulcers induced by acetic acid Below the volume of gastric acid was measured and the full dose 30mg/kg of M.I. gave the least amount of secretion indicating the potential M.I. has as a gastro-protective agent volume of gastric acid secretion volume 6 5 4 3 volume 2 1 0 control omeprazole M.I. 3mg/kg M.I. 10mg/kg M.I. 30mg/kg Continued use of Omeprazole (gastrogard) leads to virtual anacidity which when stopped causes over production of gastric acid meaning the horse becomes prone to a further recurrence of ulcers. Gastric Acid secretion total acidity total acidity 70 60 50 40 30 total acidity 20 10 0 control omeprazole M.I. 3mg/kg M.I. 10mg/kg M.I. 30mg/kg A maintenance dose of M.I. Gastro- G maintains the optimum ph level of a healthy gut Nitric oxide levels following treatment with M.I. flavonoids NO x 50 45 40 35 30 25 20 15 10 5 0 NO x control omeprazole M.I.3mg/kg M.I.10mg/kg M.I. 30mg/kg The Nitric oxide content of gastric acid secretion was reduced by the M.I. 72, 73 and 93% respectively. Nitric oxide regulates micro circulation, gastric motility, mucus and acid secretion. Anti oxidant effect of glutathione is unaltered by the use of maytenus indicating that the gastro-protective properties are not related to this mechanism glutathione 1800 1600 1400 1200 1000 800 600 400 200 0 glutathione Long term use of Omeprazole Effects absorption of calcium, vit b 12 and magnesium Alters gut bacteria, makes bones porous and fractures slow to heal Three large studies using administrative databases have implicated the use of proton pump inhibitors as a risk factor for bone fractures in humans there is no data available for horses. The relation between the use of proton pump inhibitors and fracture may involve calcium malabsorption due to induced hypochlorhydria. Summary Gastric ulcers in horses are caused by over secretion of gastric acid which damages the gut lining exposing it to injury. The recommended veterinary treatment is Gastrogard /Omeprazole Ulcer Guard which is effective but expensive; both contain omeprazole which stops gastric acid secretion (proton pump inhibitor) so potently it creates low stomach acidity which prevents protein breakdown and the absorption of the vitamins, b12, magnesium and calcium . It also predisposes to bone fragility, including sore shins and fractures, liver inflammation and tying up. Plant flavonoids which target the gastrointestinal tract are an effective ‘functional food’ alternative and compare very favourably with omeprazole in vivo and in vitro trials. Gastro –G is given as part of a one month course and then can be given at a ¼ dose for maintenance purposes. The flavonoids contained in Gastro-g are compliant with the rules of racing and there is no interaction with any other synthetic medication. Gastroprotective compounds –both proton pump inhibitors (omeprazole) and H2 antagonists (ranitidine, cimetidine) decrease or prevent gastric acid production but by different mechanisms. M.I. (Gastro-g) contains bio chemical compounds with both properties, plus anti inflammatory and analgesic compounds . Proton pump inhibitors Galactitol, Catechin, Epicatechin, Quercetin, Rutin, H2 Antagonists Arabinogalactan, mauritianin, trifolin, kaempferol Omeprazole (gastrogard) is a non competitive proton –pump inhibitor Although generally well tolerated, proton pump inhibitors may cause untoward CNS and endocrine effects as well as interference with the absorption, metabolism, and elimination of various drugs. Omeprazole is a weak base that reaches the parietal cell through the bloodstream, diffuses through the cytoplasm, and becomes activated and trapped as a sulfenamide in the acidic canaliculus of the parietal cell. It covalently binds to H+K (+)-ATPase, thereby irreversibly blocking acid secretion in response to all modes of stimulation. The main drawback to its use is its extreme potency, which leads to virtual anacidity, gastrin and ECL cell hyperplasia and hypergastrinemia. Plant compounds have no such side effects and are less potent but not less effective they have a synergistic action with the body’s own systems and do not destroy or completely inhibit vital endocrine chemical signalling pathways.