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The Catch 22 of GI Disease Chris D. Meletis, ND

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1 The Catch 22 of GI Disease Chris D. Meletis, ND
Executive Director

2 The Catch 22 of GI Disease Chris D
The Catch 22 of GI Disease Chris D. Meletis, ND The following potential conflict of interest relationships are germane to my presentation.   Equipment: N/A Speakers Bureau: N/A Stock Shareholder: N/A Grant/Research Support: N/A Consultant: Vitamin Research Products Status of FDA devices used for the material being presented: NA/Non-Clinical      Status of off-label use of devices, drugs or other materials that constitute the subject of this presentation   Enter Device or Drug Name: NA/Non-Clinical

3 Gastrointestinal Disease

4 Proactive Steps to Strengthen GI Health

5 Facts and Figures The entire length of the gastrointestinal tract is between 6-8 meters long (18 to 24 feet) Approximately 90% of digestion (and essentially all lipid digestion) takes place in the first two sections of the small intestine (duodenum and jejunum). Constipation is the most common gastrointestinal complaint in the United States, resulting in about 2 million annual primary care visits. However, most people treat themselves without seeking medical help, as is evident from the $725 million Americans spend on laxatives each year.

6 Beating the Statistics
60 to 70 million people are affected by overt diagnosable digestive diseases. Annually, an astounding 234,000 people die from GI diseases including cancer. Yet, far more people (14 million per year) end up in the hospital from non-fatal GI conditions. Adams PF, Hendershot GE, Marano MA. Current estimates from the National Health Interview Survey, National Center for Health Statistics. Vital Health Stat. 1999;10(200). National Center for Health Statistics. (Technical Appendix from Vital Statistics of the United States: Mortality) Hyattsville, Maryland: 2004. Kozak LJ, Owings MF, Hall MJ. National Hospital Discharge Survey: 2002 annual summary with detailed diagnosis and procedure data. National Center for Health Statistics. Vital Health Stat. 2005;13(158).

7 More than Diagnosed GI Disease
Tens of millions of Americans suffer from subclinical GI health issues: Decreasing their ability to absorb nutrients from their diet, supplements and even drugs. Undermining even the healthiest protocol. Contributing to underlying inflammatory burden (C-Reactive Protein).

8 Pro-Active vs. Re-Active Approach
Proactive GI health care is essential: 6 million diagnostic and therapeutic in-patient hospitalization procedures conducted annually. 1.9 million people disabled due to GI disease. Burt CW, Schappert SM. Ambulatory care visits to physician offices, hospital outpatient departments, and emergency departments: United States, 1999–2000. National Center for Health Statistics. Vital Health Stat. 2004;13(157). Collins, JG. Prevalence of selected chronic conditions: United States, 1990–1992. National Center for Health Statistics. Vital Health Stat. 1997; 10(194). Sandler RS, Everhart JE, Donowitz M, Adams E, Cronin K, Goodman C, Gemmen E, Shah S, Avdic A, Rubin R. The burden of selected digestive diseases in the United States. Gastroenterology. 2002;122:1500–1511.

9 Dion, S., Ward, T., Baker, K.; Digestion and Nutrient Absorption (powerpoint presentation); Salem State College - Sport, Fitness and Leisure Studies Dept. Dion, S., Ward, T., Baker, K.; Digestion and Nutrient Absorption (Powerpoint presentation); Salem State College - Sport, Fitness and Leisure Studies Dept.

10 Absorption As the bolus travels down the gastrointestinal tract, it is progressively broken down into elemental particles – amino acids, glucose, vitamins and minerals. These nutrients are actively or passively absorbed through the intestinal wall and into the bloodstream to provide specific nutrients and energy to the body’s cells.

11 Sites of Absorption Dion, S., Ward, T., Baker, K.; Digestion and Nutrient Absorption (powerpoint presentation); Salem State College - Sport, Fitness and Leisure Studies Dept. Illustration from a MacGraw-Hill publication, specific source not stated in presentation Illustration from a MacGraw-Hill publication

12 A Single Critical Nutrient As An Example “Iodine”

13 Iodine- An Example of Nutrient Assimilation and GI Health Iodine
NIS on the surface of enterocytes of the small intestine actively accumulates iodine. Therefore the health of the GI tract is critically important to the absorption of iodine and overall thyroid health Nicola, JP et al. The Na+/I-symporter (NIS) mediates active iodide uptake in the intestine. Am J Physiol Cell Physiol Dec 3 The degree of atrophic gastritis has been correlated to the degree of iodine deficiency and to the presence of a goiter. In addition, normal gastric mucosa contains more iodine than tissue affected by atrophic gastritis. Venturi S. et al.A new hypothesis: iodine and gastric cancer. Eur J Cancer Prev 1993;2:17–23.

14 Iodine- More Links Poland: Observed association between improved iodine supply and decrease of incidence of stomach cancer Golgowski, F. et al. Iodine prophylaxis--the protective factor against stomach cancer in iodine deficient areas. Eur J Nutr Aug;46(5): Epub 2007 May 11 Turkey: Tissue iodine levels were lower in gastric cancer tissue (approx ng I/mg protein) compared with surrounding normal tissue (approx. 41 ng I/mg protein) Gulaboglu, Mine et al. Comparison of iodine contents in gastric cancer and surrounding normal tissues Clin Chem Lab Med 2005;43(6):581–584

15 The ratio of urinary iodine to urinary creatinine in 100 patients diagnosed with stomach cancer and 84 people in a control group. •Mean urinary iodine levels were lower in the patients with stomach cancer, 61.9 microg/g creatinine, compared to microg/g creatinine in the control group. •More of the cancer patients (49.0%) had severe iodine deficiency (< 25 microg/g creatinine) than people in the control group (19.1%) (P< ). “We found the relationship between stomach cancer and iodine deficiency to be significant.” BehrouzianR, AghdamiN. Urinary iodine/creatinineratio in patients with stomach cancer. East MediterrHealth J Nov;10(6):921-4.

16 Fueling the Entire Body
The process of digestion ensures adequate nutrition to the 75 trillion cells in our body; however, if there are any changes in the chemistry or physiology of the intestinal tract, then the consequences are far-reaching. Disruptions such as infections, food intolerances, inflammation can start a chain reaction of malabsorption in the gastrointestinal tract that feeds on itself unless stopped and repaired with the correct nutrients. Many of these deficiencies begin with 2 major symptoms of gastrointestinal dysfunction: diarrhea and constipation.

17 Gastrointestinal Disorders:
diarrhea

18 Diarrhea and Malabsorption
Regardless of the type of diarrhea, nutrients do not get absorbed as efficiently into the body due to: Decreased transit time Incomplete digestion Inflammation of intestinal lumen Altered biochemical environment in the intestinal wall decreases nutrient absorption.

19 Complications of Malabsorption
Diarrhea affects the gastrointestinal system; however, it also cause severe nutritional deficiencies that affect various systems: Anemia: due to a lack of B vitamin and Iron absorption. Muscle wasting and weakness: Lack of essential minerals such as calcium, magnesium, potassium and sodium chloride as well as CoQ10. Nerve problems: Vitamin B12 deficiency can cause neurasthenias and other upper and lower motor neuron dysfunctions. Hormonal imbalance: due to lack of amino acids and fatty acids to make steroid-based hormones. Skin problems such as eczema, psoriasis, acne, premature aging due to lack of adequate electrolytes, fatty acids, protein, zinc, sulfur and collagen building nutrients.

20 Gastrointestinal Disorders:
constipation

21 Causes Constipation occurs when the colon absorbs too much water or if the colon’s muscle contractions are slow or sluggish, causing the stool to move through the colon too slowly. As a result, stools can become hard and dry. Common causes of constipation include: Lack of fiber Lack of physical activity Dehydration Medication – including laxative abuse Gastrointestinal disease: IBS, Crohn’s Neurological disorders – stroke, spinal cord injuries Metabolic endocrine disorders – diabetes, hypothyroid Systemic disorders – lupus, scleroderma Intestinal obstructions – tumors, adhesions, diverticulosis

22 http://www. helpfulhealthtips

23 Complications Anal fissures and Hemorrhoids: a common condition with chronic constipation. The hardness of the stool and constant pressure in the perineal area makes the tissue inflamed and more friable. Diverticulosis: this is the “outpouching” of the large intestine that occurs when fecal matter stays in one area too long. These pouches can later become areas of infection in the intestinal tract as fecal matter becomes entrapped in the “pouches”. Fecal impaction Lazy bowel syndrome – from laxative overuse Nutrient Deficiency – due to poor absorption Colon cancer – long term

24 Toxic Burden The body processes myriad toxins from the environment.
Many toxins are conjugated in the liver and secreted in the bile; while others are bound in the dietary fiber in the gastrointestinal tract. However, with constipation – there are two additional risks we face: Increased exposure of toxins in the bowel Increased re-up take of previously conjugated toxins back into the bloodstream.

25 GI Health Diarrhea and constipation are both symptoms of various GI disorders. Sometimes they can co-exist within one patient. The constant inability to absorb the necessary nutrients with diarrhea and the increased exposure to toxins with constipation, creates an environment in the gastrointestinal tract that is not conducive to its health and healing. Both diarrhea and constipation cause inflammation and wearing away of tissues that compromise the integrity of a person’s health and well-being.

26 Gastrointestinal Disorders:
Celiac disease

27 Cause A large US study recently (2004) reported a prevalence of celiac disease of 1/133. Prevalence rates were even higher for those with gastrointestinal symptoms (1/56) and in those with a first-degree relative with celiac disease (1/22). Celiac disease is a genetic inability to break down the gliadin proteins. When the intestinal wall is exposed to gliadins, it becomes inflamed. Tha inflammation decreases absorption of nutrients such as iron, folic acid, calcium, and fat-soluble vitamins.

28 http://www. bio. davidson

29 Intestinal Changes in Celiac
Normal villi Atrophied villi

30 Extraintestinal Signs of Celiac
Dermatitis herpetiformis Apthous ulcers

31 Symptoms Many patients have minimal symptoms, and gastrointestinal symptoms are frequently absent. When patients are symptomatic, the following symptoms are seen: Stomach pain, gas, and bloating Chronic diarrhea Pale, foul-smelling bowel movements Weight loss Bone or joint pain Dermatitis herpetiformis, a painful rash of itchy blisters Stunted growth (in children) Anemia Fatigue Infertility

32 Complications Due to the poor absorption of nutrients, patients with celiac disease can suffer from: Anemia Osteoporosis Celiac disease tend to have other diseases in which the immune system attacks the body’s healthy cells and tissues. The connection between celiac disease and these diseases may be genetic. They include: type 1 diabetes autoimmune thyroid disease autoimmune liver disease rheumatoid arthritis Addison’s disease, a condition in which the glands that produce critical hormones are damaged Sjögren’s syndrome, a condition in which the glands that produce tears and saliva are destroyed

33 Nutrient Deficiencies & Celiac Disease
Iron (Bis-glycinate) Folic acid (MTHF) Calcium Vitamin A Vitamin D Vitamin E Vitamin K

34 Iron The most common nutritional anemia associated with celiac disease is iron deficiency. Anemia without other clinical clues of intestinal malabsorption is one of the most common extraintestinal manifestations of celiac disease. Studies have found anemia in celiac disease can be due to inflammation as well as to intestinal malabsorption. Hershko C, Patz J.Ironing out the mechanism of anemia in celiac disease. Haematologica Dec;93(12):1761-5

35 Folic Acid Malnutrition and nutritional deficiencies (zinc, folic acid, vitamin A) also predispose to mucosal damage. Low folate levels are common findings in asymptomatic CD patients. Folic acid deficiencies result in GI tract disturbances because it is vital in the cellular DNA expression, particularly in rapidly multiplying cells, such as those in the gastrointestinal tract. Davidson G, Kritas S, Butler R.; Stressed mucosa. Nestle Nutr Workshop Ser Pediatr Program. 2007;59:133-42; discussion Tikkakoski S, Savilahti E, Kolho KL.;Undiagnosed coeliac disease and nutritional deficiencies in adults screened in primary health care. Scand J Gastroenterol Jan;42(1):60-5. Kim YI, Baik HW, Fawaz K, et al. Effects of folate supplementation on two provisional molecular markers of colon cancer: a prospective, randomized trial. Am J Gastroenterol. 2001;96(1):

36 Calcium & Vitamin D CD patients have a high incidence of osteoporosis.
Chronic inflammation and malabsorption in celiac disease (CD) can cause bone metabolism alterations and bone mineral loss in children and adults. Findings suggest that calcium malabsorption in celiac disease does not result from the absence of vitamin D receptors, but rather from reduction in vitamin D regulated proteins and functions essential for active calcium absorption that are located in the enterocytes of the villi. Bianchi ML, Bardella MT.; Bone in celiac disease. Osteoporos Int Dec;19(12): Epub 2008 Apr 17. K W Colston, A G Mackay, C Finlayson, J C Wu and J D Maxwell ;Localization of vitamin D receptor in normal human duodenum and in patients with celiac disease. Gut 1994;35: ; doi: /gut Copyright © 1994 BMJ Publishing Group Ltd & British Society of Gastroenterology.

37 Vitamin A & Vitamin E Carcinoma of the pharynx and esophagus, and adenocarcinoma of the small intestine, are increased in frequency in patients with celiac disease. The increased risk of carcinoma of the esophagus may be related to vitamin A deficiency. Tocopherol deficiency is implicated in the biological processes leading to malignant cell transformations, neurological complications, brown bowel syndrome and reproductive disorders. Untreated patients with CD have higher incidences of these disorders than in general population. Wright DH.; The major complications of celiac disease. Baillieres Clin Gastroenterol Jun;9(2): Hozyasz KK, Chelchowska M, Laskowska-Klita T.; [Vitamin E levels in patients with celiac disease] [Article in Polish] Med Wieku Rozwoj Oct-Dec;7(4 Pt 2): Odetti P, Valentini S, Aragno I, Garibaldi S, Pronzato MA, Rolandi E, Barreca T.; Oxidative stress in subjects affected by celiac disease. Free Radic Res Jul;29(1):17-24

38 Vitamin K Vitamin K-deficiency bleeding is a rare complication that occurs almost exclusively in patients with typical CD manifestations. Question: What about Vitamin K2? Djuric Z, Zivic S, Katic V. Celiac disease with diffuse cutaneous vitamin K-deficiency bleeding; Adv Ther Nov-Dec;24(6):

39 Gastrointestinal Disorders:
Crohn's disease

40

41 Common Nutrient Deficiencies
Vitamin A / Beta-carotene Vitamin D Vitamin E Vitamin K Vitamin C Vitamin B1, B2, B3, B12 Folic Acid (MTHF) Biotin Calcium, Magnesium , Iron, Zinc and Selenium

42 Zinc 40% of patients with Crohn's Disease have a zinc deficiency. (Zinc monomethionine) Zinc deficiency leads to common CD complications and symptoms such as acrodermatitis enteropathica, alopecia, etc. Diarrhea, mental changes, irritability, depression and decreased visual acuity, which resolve with zinc supplementation. Patients with diarrhea may lose trace minerals, and a correlation exists between stool volume and fecal losses of zinc. Myung SJ, Yang S-K, Jung H-Y, et al.; Zinc deficiency in Crohn’s disease; J9 2G4astroenterol 1998; 33:924–925

43 Vitamin B12 (Methylcobalamin)
Vitamin B12 deficiency is common in Crohn's disease. Deficiency of this vitamin can cause further inflammation of the gastrointestinal tract and increases vulnerability of gastrointestinal tract to dysplastic changes. Vitamin B12 deficiency can also cause appetite loss and stomach inflammation, which further prevent adequate B12 absorption. Food and Nutrition Board, Institute of Medicine. Vitamin B12. Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B6, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington D.C.: National Academy Press; 1998:

44 Vitamin C Vitamin C is intimately related with the integrity of connective tissue and blood vessels. Deficiency of vitamin C results in weakening of blood vessels, connective tissue, and bone, which contain collagen. Thus, in Crohn's disease, deficiency of this vitamin can further prevent healing of the intestinal mucosa which further exacerbates the lack of vitamin C absorption. Food and Nutrition Board, Institute of Medicine. Vitamin C. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington D.C.: National Academy Press; 2000:

45 Gastrointestinal Disorders:
Ulcerative colitis

46 Common Nutrient Deficiencies
Vitamin K (vitamin K2) Vitamin A Folic Acid (MTHF) Zinc Arginine (NOS-vasodilation) EFA

47 Iron (Bisglycinate) Iron deficiency and resultant anemia is frequent in UC due to chronic GI bleeding. Research on preneoplastic colonic mucosa of UC patients has demonstrated immunoreactivity to the major iron-binding proteins, lactoferrin, transferrin, and ferritin. Increased expression of these proteins and subsequent iron accumulation may trigger a self perpetuating cycle, resulting in further tissue damage and a trend toward neoplastic progression. Sturniolo GC, Tuccari G, D’Inca R, et al.; Mucosal iron concentration and immunohistochemical; evidence of iron-binding proteins in long-standing ulcerative colitis. Ital J Gastroenterol 1993;25:A68.

48 Vitamin K One of the first signs of vitamin K is a change in Prothrombin time. Studies have identified that 1/3 of patients with gastrointestinal disorders suffer from vitamin K deficiency. This study also noted that Vitamin E levels were decreased in patients with low vitamin K levels. SD Krasinski, RM Russell, BC Furie, SF Kruger, PF Jacques and B Furie; The prevalence of vitamin K deficiency in chronic gastrointestinal disorders; American Journal of Clinical Nutrition, Vol 41, , 1985.

49 Vitamin A Carotenoids and retinol play an essential role in enhancing the mucosal integrity of the gut. Retinol absorption rates were also decreased in patients with severe UC.

50 Folic Acid (MTHF) Folic acid status in ulcerative colitis patients may be influenced by: reduced dietary intake red cell hemolysis secondary to chronic drug therapy chronic diarrhea sulfasalazine therapy that interferes with absorption of folate Carruthers LB. Chronic diarrhea treated with folic acid. Lancet 1946;I: Lashner BA. Red blood cell folate is associated with the development of dysplasia and cancer in ulcerative colitis. J Cancer Res Clin Oncol 1993;119:

51 Stephania Tetrandra & Gastrointestinal Health
Tetrandrine extract improved the symptoms of ulcerative colitis in a study using an animal model of this inflammatory bowel disease. A significant improvement was observed in the disease activity index and histological score in mice given tetrandrine. Furthermore, the increase in NF-kappaB DNA binding activity was significantly reduced following administration of tetrandrine. Activity of IL-1beta, and TNF-alpha also was significantly reduced following administration of tetrandrine. According to the researchers, “The administration of tetrandrine leads to an amelioration of DSS-induced colitis, suggesting administration of tetrandrine may provide a therapeutic approach for UC.” Zhang DK, Cheng LN, Huang XL, Shi W, Xiang JY, Gan HT. Tetrandrine ameliorates dextran-sulfate- sodium-induced colitis in mice through inhibition of nuclear factor -kappaB activation. Int J Colorectal Dis Jan;24(1):5-12.

52 Irritable bowel syndrome
Gastrointestinal Disorders: Irritable bowel syndrome

53 Common Nutrient Deficiencies
Fat soluble vitamins: A, D, E, K Minerals – calcium, magnesium, iron and zinc Since IBS is a functional disorder, the nutritional deficiencies seen in this disorder are similar to those of diarrhea or constipation.

54 Clinical Tools to Break the Cycle

55 Clinical Tools to Break the Cycle
One of the main challenges in treating gastrointestinal disorders is to break the cycle of inflammation. Inflammation can be due to nutritional deficiencies as well as infections. The microflora of the gut must be balanced. Probiotics help establish a healthy intestinal environment conducive to healing, nutrient absorption and inflammation control. Replace nutrients that have been lost to ensure proper healing of the digestive tract.

56 Anti-Inflammatory Botanicals
Boswellia serrata – studies have shown this herb to be valuable in the treatment of inflammatory gastrointestinal disorders. Curcuma longa – contains curcuminoids, which have been found to have anti-oxidant and anti-inflammatory properties. Ocimum sanctum (Basil)– has been shown to have strong anti-inflammatory properties. Ernst E.; Frankincense: systematic review. BMJ Dec 17;337:a2813. doi: /bmj.a2813. Itokawa H, Shi Q, Akiyama T, Morris-Natschke SL, Lee KH. Recent advances in the investigation of curcuminoids; Chin Med Sep 17;3:11. Singh S, Nair V, Jain S, Gupta YK.; Evaluation of anti-inflammatory activity of plant lipids containing alpha-linolenic acid. Indian J Exp Biol Jun;46(6):453-6.

57 Glycyrrhiza glabra Glabridin, a functional compound of licorice, attenuates colonic inflammation in mice with (DSS) dextran sulphate sodium-induced colitis. Author: Kwon,-H-S; Oh,-S-M; Kim,-J-K Citation: Clin-Exp-Immunol Jan; 151(1):

58 Enzymes Plant Enzymes help us digest foods that our own digestive enzymes do not digest. Some studies have found that the use of plant enzymes can help celiac disease symptoms. Another study found that the use of bromelain healed mucosa in UC patients. Stenman SM, Venalainen JI, Lindfors K et al; Enzymatic detoxification of gluten by germinating wheat proteases: Implications for new treatment of celiac disease. Ann Med Apr 7:1-11. [Epub ahead of print] Phelan JJ, Stevens FM, McNicholl B et a. Coelic disease: the abolition of gliadin toxicity by enzymes from Asergillus niger. Clin Sci Molec Med 1977; 53: 35-43 Kane S, Goldberg MJ. Use of bromelain for mild ulcerative colitis. Ann Intern Med 2000;132:680.

59 Essential Fatty Acids Fish oil has been shown to decrease colonic damage and inflammation, weight loss and mortality in animal models of colitis. Fish oil supplementation in patients with inflammatory bowel diseases increases n-3 PUFA and decreases inflammation in the gut mucosa. Clinical outcomes report improved gut histology, and decreased disease activity with the use of fish oils. Resolvins, molecules that are byproducts of omega 3 fatty acids, biosynthesized by human cells via cell-cell interactions, have been shown to be potent anti-inflammatory in nature. Calder, P.C.; Polyunsaturated fatty acids, inflammatory processes and inflammatory bowel Diseases. Mol Nutr Food Res Aug;52(8): Serhan CN.; Novel eicosanoid and docosanoid mediators: resolvins, docosatrienes, and neuroprotectins. Curr Opin Clin Nutr Metab Care Mar;8(2):

60 Probiotics Probiotics are some of those supplements that can work for several different conditions. It is best seen as a normalizer, as it both acts to decrease diarrhea, and to improve constipation. Numerous studies have shown that the use of probiotics significantly improves bowel movement quality by increasing the bulk of the stool. De Paula JA, Carmuega E, Weill R.; Effect of the ingestion of a symbiotic yogurt on the bowel habits of women with functional constipation. Acta Gastroenterol Latinoam Mar;38(1):16-25. Pitkala,-K-H; Strandberg,-T-E; Finne-Soveri,-U-H; Ouwehand,-A-C; Poussa,-T; Salminen,-S Fermented cereal with specific bifidobacteria normalizes bowel movements in elderly nursing home residents. A randomized, controlled trial. J-Nutr-Health-Aging Jul-Aug; 11(4):

61 In one study, the effective rate of probiotic capsules including Lactobacillus and Bifidobacteria in the treatment of IBS was 56.8 percent by the second week, and 74.3 percent during the fourth week. Fan YJ, Chen SJ, Yu YC, et al. A probiotic treatment containing Lactobacillus, Bifidobacterium and Enterococcus improves IBS symptoms in an open label trial. J Zhejiang Univ Sci. B 2006 Dec;7(12): In another study, probiotic and prebiotic supplementation was shown to decrease nausea, indigestion, flatulence, and marginal colitis in patients with IBS at 2 weeks. At 52 weeks, the rate of IBS remissions was 81.5 percent to 100 percent. Bittner AC, Croffut RM, Stranahan MC, et al. Prescript-assist probiotic-prebiotic treatment for irritable bowel syndrome: an open-label, partially controlled, 1-year extension of a previously published controlled clinical trial. Clin Ther Jun;29(6): Studies demonstrate that probiotic-secretory proteins protect the intestinal epithelial tight junctions and the barrier function from hydrogen peroxide-induced insult. Fanigliulo L, Comparato G, Aragona G, et al; Role of gut microflora and probiotic effects in the irritable bowel syndrome. Acta Biomed Aug;77(2):85-9. Seth,-A; Yan,-F; Polk,-D-B; Rao,-R-K Probiotics ameliorate the hydrogen peroxide-induced epithelial barrier disruption by a PKC- and MAP kinase-dependent mechanism; Am-J-Physiol-Gastrointest-Liver-Physiol Apr; 294(4): G1060-9 Brenner DM, Chey WDBifidobacterium infantis 35624: A Novel Probiotic for the Treatment of Irritable Bowel Syndrome. Rev Gastroenterol Disord Winter;9(1):7-15.

62 Probiotics Probiotics, particularly Lactobacillus rhamnosus GG, have been shown to prevent and treat diarrhea in children and adults. Probiotics have various functions in the gastrointestinal tract: compete with pathogens for nutrients and receptors induce hydrolysis of toxins and receptors induce production of antimicrobial substances (including peptides of the innate immune system) induce production of organic acids and modulation of nitric oxide synthesis regulate intestinal permeability by modulating the epithelial tight junctions exert a trophic action on the intestinal mucosa, which leads to brush border enzyme activation, stimulation of glucose absorption and antiapoptotic effects on the enterocyte inhibit selected intracellular mechanisms involved in viral replication Guarino, A., Lo Veccio, A., Canani, R.B.; Probiotics as Prevention and Treatment for Diarrhea; Current Opinion in Gastroenterology. Published: 04/22/ /5/09.

63 L-Glutamine Glutamine is the most abundant free amino acid in the body. Glutamine is essential for maintaining intestinal structure. Particularly in GI disorders with high cell turn-over. Glutamine serves as metabolic fuel for enterocytes that line the colon and affect cell proliferation. The GI tract has the largest demand for glutamine in the body. Insufficient glutamine can present with atrophy, ulceration, and necrosis of the colon lining. Medina MA. Glutamine and cancer. J Nutr. 2001;131:2539S-42S. Sacks GS. Glutamine supplementation in catabolic patients. Ann Pharmacother. 1999;33: Miller AL. Therapeutic considerations of L-glutamine: a review of the literature. Altern Med Rev. 1999;4:

64 Zinc Zinc supplementation reduces the duration and severity of acute and persistent diarrhea; however, the mechanisms by which zinc exerts its anti-diarrheal effect have not been fully elucidated. Zinc supplementation in IBD has been noted to improve anti-oxidant status. Lukacik,-M; Thomas,-R-L; Aranda,-J-V; A meta-analysis of the effects of oral zinc in the treatment of acute and persistent diarrhea. Pediatrics Feb; 121(2): Roy,-S-K; Hossain,-M-J; Khatun,-W; Chakraborty,-B; Chowdhury,-S; Begum,-A; Mah-e-Muneer,-S; Shafique,-S; Khanam,-M; Chowdhury,-R; Zinc supplementation in children with cholera in Bangladesh: randomised controlled trial; BMJ Feb 2; 336(7638): 266-8 Blázovics A, Szentmihályi K, Prónai L, Hagymási K, Lugasi A, Kovács A, Fehér J.; [Redox homeostasis in inflammatory bowel diseases]; [Article in Hungarian] Orv Hetil Jul 11;145(28):

65 Berberine Berberine extracts and decoctions have demonstrated significant antimicrobial activity against a variety of organisms including bacteria, viruses, fungi, protozoans, helminths, and chlamydia. The pharmacologic actions of berberine include metabolic inhibition of certain organisms, inhibition of bacterial enterotoxin formation, inhibition of intestinal fluid accumulation and ion secretion, inhibition of smooth muscle contraction, reduction of inflammation, platelet aggregation inhibition, platelet count elevation in certain types of thrombocytopenia, stimulation of bile and bilirubin secretion, and inhibition of ventricular tachyarrhythmias. Birdsall TC, Kelly GS. Berberine: Therapeutic potential of an alkaloid found in several medicinal plants. Altern Med Rev 1997;2: Akhter MH, Sabir M, Bhide NK. Possible mechanism of antidiarrhoel effect of berberine. Indian J Med Res 1979;70:

66 5 HTP The gastrointestinal tract contains approximately 95% of the body's serotonin and colic mucosal serotonin metabolism has been reported to be altered in IBS patients. Serotonin activates both intrinsic and extrinsic primary afferent neurons to respectively initiate peristaltic and secretory reflexes and to transmit information to the central nervous system. Serotonin levels in IBS patients are altered. Supplementation with 5-HTP provides serotonin on an as needed basis to provide relief for IBS MD Gershon, “ Review article: roles played by 5-hydroxytryptamine in the physiology of the bowel”, Aliment Pharmacol Ther (1999), 13: pp Sikander A, Rana SV, Prasad KK.; Role of serotonin in gastrointestinal motility and irritable bowel syndrome. Clin Chim Acta May;403(1-2): Epub 2009 Feb 4.

67 Global Considerations
Hypoallergenic Protein Anti-Inflammatory Drink L-Glutamine DGL (DeGlycyrrhizinated Licorice) NAG (N-Acetyl-Glucosamine) Slippery Elm/Marshmallow Berberine Cabbage Phosphatidylcholine Gamma Oryzanol

68 Synergistic Products for GI Health
Powdered Anti-Inflammatory Nutrients and Botanicals Encapsulated Synergistic Approach

69 Take Home Message All the Positive Intention in the World, if not properly assimilated and welcomed into our bodies, will have less than full beneficial effect. Everyone wishing to maximize their supplement routine and wellness must also maximize their Colon Health. Thank You


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