Dietary Supplements

1. Dietary Supplements Juanita Escamilla, MS Sodexo Distance Education Dietetic Intern Professional Research Presentation December 11, 2012

2. Background and Research • BS, Food and Nutrition and MS Human Nutrition (Food Biotechnology and Molecular Nutrition) • Thesis: Role of Gut Microflora in Colon Cancer Metastasis • Studied various strains of probiotic bacteria (L. casei, L. rhamnosus GG, B. longum) • Looked at metastasis in vitro, usingvarious assays such as the Boyden Chamber, Western Blot, and Zymography • Community and Clinical Nutrition Experience • San Marcos, A Tu Salud (low-income Spanish speaking women) • San Marcos, Nutrition 101, Hernandez Intermediate School • MEND (Mind, Exercise, Nutrition, Do It) • El Hospital Para el Niño Poblano

3. Gap in Knowledge • What is the Mechanism of Action of Probiotics, D-Mannose, and Cranberry? We know they work, but how do they work?

4. Objectives • Audience will be able to: • State the definition of a Dietary supplement, Nutraceutical, and a Functional Food • State the regulation of Dietary supplements in the market • State the Mechanism of Action of Probiotics, D-mannose and Cranberry • State the recommended uses for Probiotics, D-mannose and Cranberry

5. Raise your hand if you’ve taken a Dietary Supplement?

6. Quick Facts • U.S. adult population. Over 40% used supplements in 1988–1994, and over 50% in 2003–2006 • Multivitamins/multiminerals are the most commonly used dietary supplements, with approximately 40% of men and women reporting use during 2003–2006 • Dietary supplements have been taken by more than half of American adults; consumers spent $26.7 billion on supplements in 2009 • 2011 Survey found that 1 in 4 people take a fish oil supplement

7. Reasons for Taking Dietary Supplements

8. Definition of a Dietary Supplement As defined by Congress in the: Dietary Supplement Health and Education Act (DSHEA), which became law in 1994, a dietary supplement is a product (other than tobacco) that • is intended to supplement the diet; • contains one or more dietary ingredients (including vitamins; minerals; herbs or other botanicals; amino acids; and other substances) or their constituents; • is intended to be taken by mouth as a pill, capsule, tablet, or liquid; and • is labeled on the front panel as being a dietary supplement.

9. Regulation of Dietary Supplements • The Federal Government regulates dietary supplements through the U.S. Food and Drug Administration (FDA). The regulations for dietary supplements are not the same as those for prescription or over-the-counter drugs. In general, the regulations for dietary supplements are less strict. • Dietary supplements are not required by federal law to be tested for safety and effectiveness before they are marketed, so the amount of scientific evidence available for various supplement ingredients varies widely.

10. My Dietary Supplements Mobile App https://myds.nih.gov.

11. Modern Terms • Nutraceutical: • Coined from “nutrition” and “pharmaceutical”, 1989 by Stephen DeFeleice, MD, founder and chairman of the Foundation for Innovation in Medicine (FIM) • “a food (or part of a food) that provides medical or health benefits, including the prevention and/or treatment of a disease”, go beyond supplementation, more therapeutic. • Differ from dietary supplements by the following aspects: • Nutraceuticals must not only supplement the diet but should also aid in the prevention and/or treatment of disease and/or disorder • Nutraceuticals are used as conventional foods or as sole items of a meal or diet • Examples: Green Tea, Vitamin D, Lycopene, Phytochemicals, Probiotics, etc

12. Pharmaceutical Nutrition Scientific Evidence Nutraceutical

13. Functional Foods: • Are similar in appearance to conventional foods and consumed as part of a normal diet • Demonstrated physiological benefits and can reduce the risk of chronic disease beyond basic nutritional functions, including maintenance of gut health • Academy of Nutrition and Dietetics Definition: • All foods as functional at some physiological level because they provide nutrients or other substances that furnish energy, sustain growth, or maintain/repair vital processes. However, functional foods move beyond necessity to provide additional health benefits that may reduce disease risk and/or promote optimal health. Functional foods include conventional foods, modified foods (ie, fortified, enriched, or enhanced), medical foods, and foods for special dietary use

14. Probiotics

15. Human Gut Microflora • Human GI tract is sterile at birth, microflora develops after birth • Colonization rate varies according to factors: • Mode of Birth • Infant Nutrition • Antibiotic Use • Diet • Age

16. Microorganisms that reside on and inside humans outnumber somatic cells • Influence host metabolism, physiology, gene expression • GI contains ~100 trillion microorganisms that represent 1000 separate bacteria, yeasts, parasites • Increase in numbers from the mouth to the anus

17. Probiotics and Gastrointestinal Health • Probiotic bacteria are defined as : “live microorganisms which when administered in adequate amounts confer a health benefit on the host” • Ingestion of probioticshas been shown to aid in overall gastrointestinal health: • Modulating the intestinal flora • Decreasing the number of toxin (carinogenic) producing bacteria in the large intestine. • Reduce the risk of colorectal cancer • Decrease intestinal permeabilty • Stimulation of immune functions • Improved digestion and absorption of nutrients • Synthesis of vitamins

18. Large Intestine Microflora 2 Inhibition of growth of exogenous and harmful bacteria (diarrhoea, IBD, UC, Crohn’s disease, colon cancer) Ps. aeruginosa Intestinal putrefaction Proteus sp. Staphylococci Clostridia Veillonellae Digestion/ absorption of undigested foods and minerals Enterococci Production of carcinogens E. coli Lactobacilli Stimulate immune function Streptococci Diarrhea, constipation, infections, liver damage, cancer, toxigenesis. Bifidobacteria Bacteroides Lipid lowering 11 No./g faeces (log scale)

19. Mechanism of Action in the Context of Cancer 1. Disruption of TJ proteins Primary Tumor Extracellular Membrane 2. Invasion through the ECM (increase MMP-9 activity) 3. Entrance into circulation 4. Metastasis into liver and lungs

20. Claudin ZO-3 Occludin ZO-1 JAM ZO-2 Actin • Separation of single tumor cells from primary tumor • Tight junctions regulate the epithelial barrier function by the apical intercellular junctions formed in normal epithelial cells and tumor cells. • Decreased expression of ZO-1 been implicated in cancer metastasis Paracellular Space

21. Lactobacillus sp. Decrease MMP-9 Protein Levels Control L. casei L. rhamnosus MMP-9 Ponceau S 74.22% 61.38% * * • *Indicates (P = < 0.05) Control L. casei L. rhamnosus

22. Lactobacillus sp. Increase ZO-1 Protein Levels Control L. casei L. rhamnosus ZO-1 β-actin 170.15% * 134.06% P = 0.060 • *Indicates (P = < 0.05) Control L. casei L. rhamnosus

23. What does the Data mean? Probiotics play a role in gene expression!!!!!

24. Probiotics can decrease intestinal permeability which has been implicated in autoimmune disorders such as • Thyroid disorder, Celiac Disease, Parkinson’s, Type 1 Diabetes

25. D-Mannose and Cranberry

26. Urinary Tract • Works with the lungs, skin, and intestines to excrete wastes to maintain homeostasis in the body. • Urinary tract infections can occur and are caused by bacteria in the urinary tract. • CAUTI, Cystitis (bladder), pyelonephritis (kidney) • In the United States, 1 in 5 women report reoccurring UTI, eleven million women receive medication for UTIs annually • Treatments include: antibiotics, increasing fluid intake to flush out bacteria

27. Urinary Tract and Infection • “Bacterial adherence to the uroepithelium is recognized as an important mechanism in the initiation and pathogenesis of urinary tract infections (UTI). The uropathogens originate predominantly in the intestinal tract and initially colonize the periurethral region and ascend into the bladder, resulting in symptomatic or asymptomatic bacteriuria.”

28. D-mannose and Cranberry • d-Mannose is the end product of the digestion of various polysaccharides and glycoproteins found in the diet. • d-Mannose is a monosaccharide found in fruits such as apples, blueberries, and cranberries. • Cranberries (Vaccinium macrocarpon) contain high levels of d-Mannose as well as proanthocyanins (PACs). • Both d-Mannose and PACs have been shown to prevent and treat UTI infections in both men and women

29. Mechanism of Action E. coli d-Mannose Receptor d-Mannose Cranberry Eroepithelial Cells

30. Summary • Dietary Supplements, nutraceuticals, and functional foods fall under DSHEA and are regulated by the federal government with more lenient standards. • Probiotics aid in overall GI Health by mechanisms that affect gene expression, specifically through Tight Junction Proteins and MMP-9 in the context of cancer. • D-mannose and Cranberry have been shown to prevent and treat urinary tract infections by preventing pathogenic bacteria from binding to uroepithelium.

31. THANK YOU!!!! Grazie Merci Gracias

32. Resources • Dietary Supplement Health and Education Act of 1994. U.S. Food and Drug Administration Web site. Accessed at http://www.fda.gov/RegulatoryInformation/Legislation/ on November 24, 2012. • Dietary supplements: background information. Office of Dietary Supplements Web site. Accessed at ods.od.nih.gov/factsheets/DietarySupplements_pf.asp on November 20, 2012. • Dietary supplements: overview. U.S. Food and Drug Administration, Center for Food Safety and Applied Nutrition Web site. Accessed at www.fda.gov/Food/DietarySupplements/ on November 20, 2012. • Natural Medicines Comprehensive Database. Product monographs. Accessed at www.naturaldatabase.com on November 20, 2012. • Radimer K, Bindewald B, Hughes J, et alDietary supplement use by US adults: data from the National Health and Nutrition Examination Survey, 1999–2000. American Journal of Epidemiology. 2004;160(4):339–349. • What’s behind our dietary supplements coverage. Consumer Reports. Accessed http://www.consumerreports.org/cro/2012/04/what-s-behind-our-dietary-supplements-coverage/index.htm

33. Radimer K, Bindewald B, Hughes J, Ervin B, Swanson C, Picciano MF. Dietary supplement use by US adults: data from the National Health and Nutrition Examination Survey, 1999-2000. Am J Epidemiol. 2004;60(4):339-49. • FAO/WHO: Regulatory and clinical aspects of dairy probiotics. Food and Agriculture Organization of the United Nations and World Health Organization Expert Consultation Report. 2001. • Supplement Use Widespread Among Americans. Medline Plus U.S National Library of Medicine NIH website. Assessed at http://www.nlm.nih.gov/medlineplus/news/fullstory_131502.html on November 22, 2012. • Bajzer M, Seeley RJ. The intestinal bacteria in obese humans and mice differ from those lean individuals. Are these bacteria involved in how we regulate body weight, and are they a factor in the obesity epidemic? Nature 2006; 444: 1009-1010. • Cencic A, Chingwaru W. The Role of Functional Foods, Nutraceuticals, and Food Supplements in Intestinal Health. Nutrients 2010; 2: 611-625. • Position of the American Dietetic Association: Functional Foods. J Am Diet Assoc. 2009; 109(4): 735-746. • Lynch, DM. Cranberry for Prevention of Urinary Tract Infections. Am Fam Physician. 2004; 70(11):2175-2177.

34. Millen AE, Dodd KW, Subar AF. Use of vitamin, mineral, nonvitamin, and nonmineral supplements in the United States: The 1987, 1992, and 2000. National Health Interview Survey results. J Am Diet Assoc. 2004;104(6):942-50. • Reid G, Sobel JD. Bacterial Adherence in the Pathogenesis of Urinary Tract Infection: A Review. Clin Infect Dis. 1987; 9(3):470-487. • Visser J, Rozing J, Sapone A, Lammers K, Fasano A. Tight junctions, intestinal permeability, and autoimmunity: celiac disease and type 1 diabetes paradigms. Ann N Y Acad Sci. 2009; 1165: 195-205. • Miele L, Valenza V, La Torre G, Montalto M, Cammarota G, Ricci R, Masciana R, Forgione A, Gabrieli ML, Perotti G, Vecchio FM, Rapaccini G, Gasbarrini G, Day CP, Grieco A. Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease. Hepatology. 2009; 49(6):1877-87. • Perez-Lopez FR, Haya J, Chedraui P. Vaccinium macrocarpon: an interesting option for women with recurrent urinary tract infections and other health benefits. J Obestet Gynaecol Res. 2009; 35(4):630-639. • Pappas E, Schaich KM. Phytochemicals of cranberries and cranberry products: characterization, potential health effects, and processing stability. Crit Rev Food Sci Nutr. 2009; 49(9):741-781.

35. D-Mannose for UTI Pain Relief, Treatment, and Prevention. Integrative Health Review A Resource from the National University System Center for Integrative Health. Assessed at http://www.integrativehealthreview.com/eating-nutrition/d-mannose-the-simple-sugar-that-prevents-and-can-cure-urinary-tract-infections/. December 01, 2012. • Reid G, Sobel J. Bacterial Adherence in the Pathogenesis of Urinary Tract Infection: A Review. Clin Infect Dis. 1987; 9(3):470-487. • Kaper J, Nataro J, Mobley HLT. Pathogenesis of urinary tract infection caused by uropathogenic E. coli. 2004; 2:123-140.