1. Carbonated Beverages and Upper GI Disorders What Is the Evidence? Ronnie Fass, MD. Professor of Medicine University of Arizona

2. Changes in Intraesophageal pH During Ingestion of Carbonated Beverage (A) and Coffee (B) Agrawal A et al. Dig Dis Sci 2005;50(10):1916-1920

3. Comparison of Percentage of Time of pH < 4.0 for Test and Drink Periods Shoenut J P et al. Dig Dis Sci 1998;43(4):834-839 Total time of pH <4.0 (%) Time during drink of pH <4.0 (%) Water (N=32) 9.2  9.617  40 Coffee/tea N=35) 5.9  7.317  68 Juice (N=29) 9.0  11.451  57 Coke (N=34) 6.5  5.263  47 Beer (N=12) 7.7  6.417  17

4. Comparison of Minutes of pH <4.0, 10 Minutes Before and After Drink Shoenut J P et al. Dig Dis Sci 1998;43(4):834-839 10 min prior to drink 10 min following drink Water (N=32) 0.86  1.740.87  2.60 Coffee/tea N=35) 0.41  1.700.82  2.30 Juice (N=29) 0.16  0.400.43  1.20 Coke (N=34) 0.48  1.000.83  1.63 Beer (N=12) 0.65  1.304.21  11.00

5. Number of Total Gastroesophageal Refluxes Recorded by pH Impedance 1 H Before and 4 H After Meal (N = 15) B 1 = Still waterB 2 = Sprite© without CO 2 B 3 = Sprite © with CO 2 P < 0.05 vs basal level Cuomo et al. Neurogastroenterol Motil 2008;20:780-789

6. Diet, Lifestyle and Gender in Gastroesophageal Reflux Disease Dore MP et al. Dig Dis Sci 2007 Nov 22. [Epub ahead of print] Assessment of risk factors associated among 3,000 patients presenting with GERD versus 200 controls Positive: Being femaleOR = 2.1 Lack of college educationOR = 2.1 ObesityOR = 1.8 Not associated: Soda consumption

7. Level of Evidence Kaltenbach T et al. Arch Intern Med 2006;166:965-971 Evidence AOne or more well-designed randomized controlled clinical trials with consistent evidence Evidence BCohort or case-control trials, nonrandomized or uncontrolled clinical trials Evidence C Case reports, flawed clinical trials, population studies Evidence D Expert or investigator opinion Evidence EInsufficient evidence or trials with significantly conflicting data

8. Summary of Physiologic Evidence for Gastroesophageal Reflux Kaltenbach T et al. Arch Intern Med 2006;166:965-971 FactorTrials, No. Lowered LESP Worsened pH Worsened Symptoms Tobacco12BBB Alcohol16No effect (B)BB Obesity24EEE Coffee and caffeine14EENo effect (C) Chocolate2BBE Spicy foods2EEC Citrus3No effect (B)EC Carbonated beverages2BEC Fatty foods9DBE Mint1DEE Recumbent position1EBB RLD position3BBE Late-evening meal3ENo effect (B)E

9. –For esophageal adenocarcinoma – OR = 0.71 (95% CI = 0.49-1.03) –For esophageal adenocarcinoma (after adjustment for risk factors) – OR = 0.47 (95% CI = 0.29-0.76) –For noncardia adenocarcinoma – OR = 0.65 (95% CI = 0.4-0.98) Overall, high carbonated soft drink consumption was associated with reduced risk of esophageal adenocarcinoma in men and women. High Carbonated Soft Drink Consumption and Risk for Upper GI Cancer Mayne S et al. J Natl Cancer Inst 2006; 98(1):72-75

10. Distribution of 304 Squamous Cell Esophageal Cancer Case Patients and Corresponding 743 Control Subjects, According to Consumption of Carbonated Soft Drinks (CSD), Italy 1992-1997 CSD Regular Drinkers (  1 glass/day) All CSD drinkers (  1 glass/mo) CharacteristicCase/ControlsOR (95% CI)Case/ControlsOR (95% CI) Sex Men Women 41/98 4/22 0.80 (0.49-1.29) 0.70 (0.15-3.19) 92/220 10/48 0.82 (0.57-1.18) 1.11 (0.38-3.27) Age, y <60  60 27/63 18/57 0.94 (0.50-1.78) 0.86 (0.44-1.69) 61/37 41/131 1.09 (0.67-1.78) 0.69 (0.43-1.12) Gallus S et al. J Natl Cancer Inst 2006;98(9):645-646

11. Total Stomach Emptying of Liquid Component of Mixed Solid/Liquid Meal with Sparkling versus Still Water Pouderoux et al. Dig Dis Sci 1997;42(1):34-39 P < 0.05 sparkling water versus still water N = 8

12. Total Stomach Emptying of Solid Component of Mixed Solid/Liquid Meal with Sparkling versus Still Water Pouderoux et al. Dig Dis Sci 1997;42(1):34-39 P < 0.05 sparkling water versus still water N = 8

13. Mean Visual Analogue Scale of (a) Hunger, (b) Fullness, (c) Desire to Eat and (d) Thirst Before Carbonated Beverage Preload Until 18 Minutes Post Consumption for Women (N=15) Moorhead et al. Br J Nutr 2008;99:1362-1369

14. Half Gastric Emptying Time and Percent of Gallbladder Emptying Contraction with 3 Beverages (N = 15) Cuomo et al. Neurogastroenterol Motil 2008;20:780-789 B1 = Still water B2 = Sprite© without CO2 B3 = Sprite © with CO2 Dashed line = Mean P = all NS

15. Predictive Factors for Peptic Ulcer Disease in Greece (N=295) Predictive –Family history –Smoking –Alcohol consumption –H pylori infection Not predictive –Education level –Area of residence –Cola drink consumption Archimandritis A et al. Ann Med Interne (Paris) 1995:146:299-303

16. Dyspepsia Scores Before and After Each Water Treatment Before After Before After Means are indicated by a short horizontal line in each column of data. Cuomo R et al. Eur J Gastroenterol Hepatol 2002, 14:991-999

17. Constipation Scores Before and After Each Water Treatment Cuomo R et al. Eur J Gastroenterol Hepatol 2002, 14:991-999 Means are indicated by a short horizontal line in each column of data.

18. Colonic Transit Time and Gastric Emptying Parameters in the Two Treatment Groups Cuomo R et al. Eur J Gastroenterol Hepatol 2002, 14:991-999 Carbonated Water GroupTap Water Group BeforeAfterBeforeAfter Colonic transit time (total transit; h) 40.8  18.035.6  10.256.4  38.253.6  30.6 Gastric emptying (half time; min) 76.6  12.668.4  16.194.8  22.478.9  21.4 Rate (% per min) 0.64  0.140.70  0.160.57  0.140.64  0.14 Lag time (min.) 19.9  7.716.2  7.021.1  13.916.2  12.7

19. Therapeutic Usage of Carbonated Beverages such as Cola in Gastroenterology 1.Oral hydration for diarrhea (acute and chronic) 2.Declogging feeding tubes 3.Cleaning barium prior to upper endoscopy 4.Bezoar removal 5.Clearance of esophageal food impaction