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Nutritional Management of Upper GI Disorders Mitchell A. Fleisher, M.D., D.Ht., D.A.B.F.M. Review of the Fundamentals UGI Disorders Dyspepsia Symptoms include: Abdominal discomfort Indigestion Bloating Belching Nausea Regurgitation UGI Disorders Gastritis defined as acute or chronic inflammation of gastric mucosa, with or without erosion Symptoms similar to dyspepsia, but more severe and/or persistent Gastric and duodenal mucosa protected by: Mucus barrier on mucosa Bicarbonate buffering of acid Rapid removal of excess acid Rapid repair of mucosal tissue UGI Disorders Gastritis, due to: H. pylori infection Tobacco Alcohol Aspirin NSAIDs Stress Atrophy UGI Disorders Atrophic gastritis Loss of parietal cells in atrophic gastric mucosa due to autoimmune activity Causes hypochlorhydria (decreased HCl production) or achlorhydria (loss of HCl production) Decrease or loss of intrinsic factor secretion resulting in B12 malabsorption, and pernicious anemia Gastritis Gastroesophageal Reflux Disease GERD defined as symptoms and/or mucosal damage caused by abnormal reflux of gastric contents into esophagus Symptoms include burning sensation in the stomach and/or chest, heartburn, regurgitation, or both, esp. after meals, which are aggravated by recumbency, bending forward, and relieved by oral antacids Hiatal Hernia Defined as an outpouching of a portion of the stomach into the chest through the esophageal hiatus of the diaphragm Heartburn after heavy meals, certain foods, esp. spicy, and/or reclining after meals May worsen GERD symptoms Anatomy of Hiatal Hernia and GERD UGI Disorders Peptic Ulcer Disease defined as erosion through mucosa into submucosa May be gastric and/or duodenal Due to: H. pylori, Aspirin, NSAIDs, Stress (severe burns, trauma, surgery, shock, renal failure, radiation, prolonged ICU stay) May be asymptomatic, or, symptoms similar to dyspepsia or gastritis Risks of hemorrhage, perforation, and penetration into adjacent organs Gastric and Duodenal Ulcers Gastric ulcer formation involves inflammation of acid-producing, parietal cells, but usually occurs with low acid secretion Duodenal ulcers are associated with high acid secretion, and low bicarbonate secretion Hemorrhage and increased mortality are more often associated with gastric ulcers Review of the Fundamentals Diagnosis is empirical, though symptoms may not correlate with the degree of UGI mucosal inflammation and/or damage UGI Endoscopy is utilized to confirm ulceration and/or dysplasia, e.g., Barrett's esophagitis, as well as to rule out malignant pathology Negative endoscopic exam does not rule out presence of GERD Review of the Fundamentals Upper gastrointestinal disorders, including dyspepsia, GERD, gastritis, and peptic ulcer disease, are very prevalent, affecting 45% of Americans in a given, three month period (Prevalence and socioeconomic impact of upper gastrointestinal disorders in the United States: results of the U.S. Upper Gastrointestinal Study. Camilleri et al. Clin. Gastroentrol. Hepatol. 2005 Jun;3(6):543-52.) Review of the Fundamentals Helicobacter pylori is a gram-negative, spiral, flagellated microorganism that infects the gastric mucosa, leading to chronic gastritis It has been linked to the increased risk for development of ulcer disease in patients on nonsteroidal anti-inflammatory drugs, and as a potential contributor to functional, non-ulcer dyspepsia and GERD (http://www.webmd.com/digestive-disorders/h-pylori-helicobacter-pylori) Review of the Fundamentals Helicobacter pylori infection is the primary, causative and/or contributing, pathogenetic agent in a very large percentage of upper gastrointestinal disorders Research reveals that most ulcers, i.e., 80% of stomach ulcers, and 90% of duodenal ulcers, develop due to Helicobacter pylori infection (http://www.webmd.com/digestive-disorders/h-pylori-helicobacter-pylori) Helicobacter pylori Bacterium Helicobacter pylori Invasion of Gastric Mucosa Helicobacter pylori Gastric Cytopathology Destruction of Mucus Barrier and Mucosal Erosion Helicobacter pylori Gastritis Endoscopic View of Infected Gastric Mucosa Helicobacter pylori Gastric Histopathology Destruction of Gastric Mucosal Architecture Problems with Conventional Pharmacotherapy of UGI Disorders Neutralization or inhibition of gastric acid by antacids, H2 blockers and/or proton pump inhibitors leads to lack of activation of gastric protease enzymes When neutralized, gastric chyme enters duodenum, the usual, acidic stimulus to bile and pancreatic digestive enzyme secretion is absent causing undersecretion Results in inadequate digestion and malabsorption of proteins, lipids, carbohydrates, and fat-soluble vitamins, with subsequent, relative malnutrition Suboptimal macronutrient and micronutrient assimilation undermines the protective, mucus barrier, and promotes poor healing of injured, UGI mucosa Problems with Conventional Pharmacotherapy of UGI Disorders Dr. David Graham, M.D., a world renowned, medical authority on Helicobacter pylori infection stated in a 2008 report: "Traditional triple therapy remains effective only when used to treat infections with susceptible organisms.” "The prevalence of antibiotic resistance has increased to such an extent that, to maintain acceptable cure rates, all patients should be considered as having resistant infections.” (i.e., if you have H. pylori, it is highly likely that you have a resistant strain that will not be killed by conventional triple therapy) "Therapies that do not reliably yield 90% cure rates should not be prescribed empirically; triple therapies that contain combinations of a PPI, amoxicillin, clarithromycin or metronidazole now typically yield cure rates less than 80% and are no longer acceptable as empiric therapy.” Graham, D. and Shiotani, A. New Concepts of Resistance in the Treatment of Helicobacter pylori. Nature Clinical Practice Gastro & Hep. 2008, http://www.medscape.com/viewarticle/574479 Problems with Conventional Pharmacotherapy of UGI Disorders There are multiple, adverse drug reactions Problems with Conventional Pharmacotherapy of UGI Disorders Gaby, A. R. helicobacter pylori Eradication: are there alternatives to antibiotics? Altern Med Rev. 2001 6 (4):355-366 Therapy of UGI Disorders Dyspepsia Avoid offending foods Check for food sensitivities Avoid overindulgence Eat slowly and chew food thoroughly Therapy of UGI Disorders Gastritis Avoid foods and drugs that increase gastric acid secretion, e.g., chocolate, black or red pepper, coffee (even decaf.), caffeine, alcohol, tobacco Identify foods that irritate gastric mucosa, or are not generally tolerated by the individual patient Eliminate food allergens from diet Support gastric mucosal barrier Eradicate H. pylori infection Therapy of UGI Disorders GERD Restrict foods that decrease LES pressure, e.g., chocolate, coffee, mint, high fat content food Avoid or greatly limit alcohol intake Avoid eating within 3 hours before bedtime Eat smaller, more frequent meals Remain upright after eating for one hour Wear loose-fitting clothing around waist Raise the head of bed for sleep, i.e., use 30 to 45 degree wedge pillow, etc. Initiate smoking cessation (lowers LES pressure) Initiate weight reduction, if overweight or obese Therapy of UGI Disorders Peptic Ulcer Disease Follow general guidelines for gastritis Must avoid all alcohol and tobacco use Must avoid aspirin, NSAIDs, corticosteroids Critical to eradicate H. pylori infection due to high incidence of recurrence of PUD Nutriceutical Therapy of UGI Disorders Gastro Pro Specially designed, nutriceutical complex, containing Deglycyrrhizinated licorice root (DGL), Neem Leaf Powder (Azadirachta indica), Mastic Gum (Pistacia lentiscus), Bovine Colostrum, and L-Glutamine Significantly supports healthy gastrointestinal system integrity and function, especially of the stomach, esophagus and intestines Indicated for acute and chronic gastritis, peptic ulcers, GERD, inflammatory bowel disease, and intestinal permeability disorders, particularly those caused by Helicobacter pylori infections Mechanisms of Action of Gastro Pro DGL A human study concluded that Deglycyrrhizinated licorice root (DGL) is more effective at alleviating duodenal ulcers than Cimetidine Brogden, R. N., et al. Deglycyrrhizinised liquorice: a report of its pharmacological properties and therapeutic efficiency in peptic ulcer. Drugs. 8(5):330-339, 1974 Another human study concluded that DGL caused a reduction in gastric ulcer size in 78% of subjects and caused complete healing of gastric ulcers in 44% of subjects Glick, L. Deglycyrrhizinated liquorice in peptic ulcer. The Lancet. 2:817, 1982 DGL is useful for repairing the damaged cells in intestinal permeability Tewari, S. N., et al. Deglycyrrhizinated licorice in duodenal ulcer. Practitioner. 210:820823, 1973) Mechanisms of Action of Gastro Pro Neem Leaf Powder (Azadirachta indica) Helps to alleviate peptic ulcer disease (PUD), i.e., gastric and duodenal ulcers, through the suppression of Helicobacter pylori infections that are responsible for many cases of PUD Subapriya, R., et al. Medicinal Properties of Neem Leaves: A Review. Current Medicinal Chemistry-Anti-Cancer Agents, Vol. 5, No. 2, March 2005, pp. 149-156(8) Kiranmai M, et al. Evaluation of Anti-helicobacter pylori activity and total flavonoids content of Azadirachta indica extracts. Department of Pharmaceutical Chemistry, Nizam Institute of Pharmacy, Pochampally(M), Deshmukhi, Nalgonda-508284 Mechanisms of Action of Gastro Pro Mastic Gum (Pistacia lentiscus) A double-blind clinical trial was carried out on thirty-eight patients with symptomatic and endoscopically proven duodenal ulcer to compare the therapeutic responses to mastic gum and placebo administered for two weeks Symptomatic relief was obtained in sixteen (80%) patients on mastic gum and in nine (50%) patients on placebo, while endoscopically proven healing occurred in fourteen (70%) patients on mastic and four (22%) patients on placebo The differences between treatments were highly significant Mastic gum was well tolerated and did not produce side effects The authors concluded that mastic gum has a significant, ulcer healing effect In addition to helping heal peptic ulcers caused by Helicobacter pylori, mastic gum can also promote healing of PUD caused by other factors, including NSAIDs and stress Al-Habbal, M. J., et al. A double-blind controlled clinical trial of mastic and placebo in the treatment of duodenal ulcer. J. Clin Exp Pharm Physiol. 11:541-544, 1984 Mechanisms of Action of Gastro Pro Mastic Gum (Pistacia lentiscus) Other research has shown that, even in low doses, mastic gum (1,000- 2,000 mg per day for two weeks) can promote very rapid healing of PUD Mastic gum is highly active against Helicobacter pylori infection It kills seven strains of Helicobacter pylori irrespective of the strain’s degree of susceptibility to nitroimidazole antibiotics (some strains of Helicobacter pylori have developed resistance to the effects of nitroimidazoles) Effectiveness of mastic gum against Helicobacter pylori is regarded as equal to or better than conventional, pharmaceutical antibiotics Dabos, KL, et al. The effect of mastic gum on Helicobacter pylori: a randomized pilot study. PhytoMedicine. 2010 Mar;17(3-4):296-9 Huwez, F. U., et al. Mastic gum kills Helicobacter pylori. New England Journal of Medicine. 339(26):1946, 1998 Marone, P., et al. Bactericidal activity of Pistacia lentiscus mastic gum against Helicobacter pylori. J. Chemother. 13(6):611-614, 2001 Mechanisms of Action of Gastro Pro Bovine Colostrum Helicobacter pylori infection is known to be the primary, causative agent of chronic gastritis and duodenal ulcers, and has been linked to gastric adenocarcinoma and lymphoma of the stomach In a controlled trial, bovine colostrum was shown to inhibit the ability of H. pylori to bind to receptors on the intestinal surface, blocking a critical step in pathogenesis The authors suggest that bovine colostrum may be an effective preventive agent against Helicobacter pylori-induced ailments Bitzan, et al. Inhibition of Helicobacter pylori and Helicobacter mustelae binding to lipid receptors by bovine colostrum. J Infect Dis. 177:955-961, 1998 Mechanisms of Action of Gastro Pro Bovine Colostrum Non-steroidal anti-inflammatory drugs (NSAIDs) cause GI injury Bovine colostrum is a rich source of growth factors A study examined whether spray dried, defatted colostrum could reduce gastrointestinal injury caused by indomethacin The authors concluded that bovine colostrum could provide a novel, inexpensive approach for the prevention and treatment of the injurious effects of NSAIDs on the gut, and may also be of value for the treatment of other ulcerative bowel conditions Recent studies suggest that colostral fractions, or individual peptides present in bovine colostrum, might be useful for the treatment of a wide variety of gastrointestinal conditions, including inflammatory bowel disease Playford, R. J., et al. Colostrum and milk-derived peptide growth factors for the treatment of gastrointestinal disorders. American Journal of Clinical Nutrition. 72(1):5-14, 2000 Playford, R. J., et al. Bovine colostrum is a health food supplement which prevents NSAID induced gut damage. Gut. 44(5):653-658, 1999 Mechanisms of Action of Gastro Pro L-Glutamine Most abundant, conditionally essential amino acid in body Significantly enhances the general health of the entire GI tract, which uses it as its primary, cellular energy source Required for the proper function of the gallbladder and pancreas Alleviates intestinal permeability due its role as a fuel for enterocytes, second only to short-chain fatty acids Serves as an important, nitrogen source for the cells of the small intestine Plays a major role in maintaining mucosal cell integrity and gut barrier function Souba, W. W. Glutamine: Physiology, Biochemistry and Nutrition in Critical Illness. Landes Co. Austin, Texas, USA. 1992 Mechanisms of Action of Gastro Pro L-Glutamine Has been clinically demonstrated to support the healing of gastritis and peptic ulcers Therapeutic doses of glutamine increase mucosal thickness and intestinal villous height, as well as increasing the secretion of IgA, which serves to decrease bacterial adherence and bacterial translocation, and strengthen the intestinal wall Useful for repairing damage to the intestines in irritable bowel syndrome and inflammatory bowel disease Glutamine deficiency can result in atrophy of the gut mucosa, decreased gut-associated lymphoid tissue (GALT), and increased intestinal permeability Miller, A. L. Therapeutic considerations of L-glutamine: a review of the literature. Alternative Medicine Review. 4:239-248, 1999 Shive, W., et al. Glutamine in treatment of peptic ulcer. Tex J Med. 53:840-843, 1957 Recommended Indications for Gastro Pro Supports prevention and control of inflammatory disorders of the gastrointestinal system Helps prevent and/or eliminate Helicobacter pylori infections of the gastrointestinal tract Promotes healing of acute and chronic inflammation of the gastrointestinal system Supports healthy, gastrointestinal functional integrity, normal digestion and intestinal permeability Helps prevent and/or promote healing of acute and chronic gastritis, peptic ulcers, GERD and inflammatory bowel disorders Recommended Dosage of Gastro Pro For gastrointestinal disorders due to Helicobacter pylori infection, dosage is four capsules three times daily between meals on a nearly empty stomach for two to four weeks, then four capsules twice daily for three months, and then two capsules twice daily thereafter for prevention of recurrence Children between 2 and 6 years old may be given half of the above-recommended adult dosages Contents of capsules may be mixed into a small amount of applesauce or other fruit jam or preserves for ease of administration in children and/or the elderly Nutriceutical Therapy of UGI Disorders In addition to Gastro Pro: For Dyspepsia and GERD, give digestive enzymes and probiotics For Atrophic Gastritis, give digestive enzymes, probiotics, acidifier and sublingual vitamin B12 Digestin 1 to 2 capsule(s) with every meal AcidaZyme 1 to 2 capsule(s) with every meal Broad Spectrum Probiotic 1 to 2 tablet(s) daily B-12 Lingual 1 to 2 tablet(s) daily B-12 Intrinsic Factor 1 to 2 capsule(s) daily Gastro Pro and above nutraceutical agents are available from Progressive Labs at (800) 527-9512, order #7876 "The doctor of the future will give no medicine, but will interest his patients in the care of the human frame, in diet, and in the cause and prevention of disease." Thomas Edison