University of Pittsburgh



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ABSTRACT

Objective: To present an integrative review of literature on the effects of gluten on gastrointestinal symptoms in individuals who do not have celiac disease.

Background: Despite a rapid increase in the number of people who identify as “gluten free,” the prevalence of celiac disease has remained roughly the same. Previous literature testing the effect of gluten on gastrointestinal symptoms has not been conclusive.

Public Health Significance: Many people believe that being “gluten free” is healthier, when in fact gluten-free products often contain more fats and sugars and cost more financially. This diet trend poses a risk on the health of our population.

Data Sources: The electronic databases of PubMed and OVID were used to identify studies using the key words “gluten free diet,” “irritable bowl syndrome,” and “non-celiac gluten sensitivity.”

Study Selection: Using exclusion and inclusion criteria 427 articles’ titles and abstracts were scanned for relevance to adhering to a gluten free diet and specifically addresses patients with non-celiac gluten sensitivity. Further review of references produced four articles. Thirteen articles were read in full. Six studies fully met inclusion and exclusion criteria for full in-depth review.

Data Synthesis: Based on their findings, studies were either categorized as concluding no significant effect of gluten or significant effects of gluten on gastrointestinal symptoms.

Conclusions: Substantially larger, multi-center research studies need to be conducted in order to truly understand the impact of gluten, if any, on gastrointestinal symptoms in non-celiac disease individuals. While some of the studies conclude there are significant detrimental effects as a result of consuming gluten, other studies conclude no significant changes in symptoms.

TABLE OF CONTENTS

preface x

1.0 Introduction 1

1.1 Purpose 3

1.2 Chapter Summaries 3

2.0 BACKGROUND 5

2.1 What is gluten? 5

2.1.1 What is celiac disease? 5

2.1.2 What causes celiac disease? 6

2.1.3 What are the negative outcomes of celiac disease? 7

2.2 Non Celiac Gluten Sensitivity (NCGS) 7

2.3 Why is there an increase in identifying as “gluten-free?” 7

3.0 METHODS 9

4.0 RESULTS 10

4.1 No gluten effect 10

4.2 Gluten Effect 12

5.0 DISCUSSION 16

5.1 Implications for future research 18

6.0 PUBLIC HEALTH SIGNIFICANCE 20

7.0 CONCLUSION 21

APPENDIX A: STUDIES INCLUDED IN INTEGRATIVE REVIEW 22

APPENDIX B: DIAGRAM 24

BIBLIOGRAPHY 25

List of tables

Table 1. Gluten Products 2

Table 2. Gluten Free Products 2

Table 3. Articles synthesized by study result 22

List of figures

Figure 1. Diagram of study selection for integrative review 24

Introduction

Over the last decade, a debate has been sparked in both the food and medical worlds over gluten and if the general population should avoid eating products that contain gluten. Some people believe that everyone should avoid consuming food that contains gluten, but others believe that people should only adhere to a gluten-free diet if it is deemed medically necessary. In 2013, Harry Blazer, who is the author of Eating Patterns in America, reported that 30% of the population self-reported following a gluten free diet (Blazer, 2013). Blazer attributes this high percentage to the general population following the trendy diet of today, and compares the gluten-free diet to past health fads like avoiding sugars and fats. Not only do gluten free products cost more financially, but in reality, gluten free foods actually have a higher sugar and fat content compared to their gluten counterparts (see Tables 1 and 2).

Table 1. Gluten Products

|Food |Price ($) |Calories |Total Fat (g) |Sodium (mg) |

|No significant effect|Biesiekierski et|Double blind randomized placebo |34 participants |No significant differences|

|of gluten on |al, 2011 |controlled trial | |in biomarkers |

|gastrointestinal |Melbourne, |1/3 response rate to study | | |

|symptom |Australia |advertisements | | |

| |Biesiekierski et|Re-challenge study |37 participants for phase |No significant findings on|

| |al, 2013 |Double blind cross over trial |I |the effect of gluten, |

| |Melbourne, | |22 participants for |specific or |

| |Australia | |re-challenge |dose-dependent, in |

| | | | |participants with NCGS on |

| | | | |a low FODMAP diet |

| | | | |No significant differences|

| | | | |in symptoms between |

| | | | |treatment groups |

| | | | |(p > .209) |

|Significant effect of|Elli et al, |Double blind placebo controlled cross |140 participants enrolled |Significant increase of |

|gluten on |2016 |over trial |98 underwent challenge |symptoms when consuming |

|gastrointestinal |Italy |5.6g of gluten per day | |gluten, compared to the |

|symptoms | | | |placebo |

| |Carroccio et al,|Retrospective study to identify study |150 controls identified by| |

| |2012 |controls |medical charts | |

| |Italy |Double blind placebo controlled |920 study participants | |

| | |challenge | | |

| |Di Sabatino et |Double blind randomized placebo |61 participants enrolled, |Significant increase of |

| |al, |controlled cross over trial |59 completed study |intestinal symptoms during|

| |2015 |4.375g of gluten per day | |gluten consumption (p < |

| |Italy | | |0.0001) |

| | | | |Significant increase of |

| | | | |extraintestinal symptoms |

| | | | |during gluten consumption |

| | | | |(p < 0.0001) |

| |Shahbazkhani et |Double blind randomized placebo |148 participants enrolled,|Significant increase of |

| |al, 2015 |controlled trial |72 completed study |symptoms for participants |

| |Iran |100g of gluten per day | |in the gluten group (p = |

| | | | |0.0001) |

*NCGS – Non celiac gluten sensitivity

APPENDIX B: DIAGRAM

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Figure 1. Diagram of study selection for integrative review

BIBLIOGRAPHY

Asero, R., Fernandez-Rivas, M., Knulst, A., Bruijnzeel-Koomen, C. (2009). Double-

blind, placebo-controlled food challenge in adults in everyday clinical practice: a reappraisal of their limitations and real indications. Curr Opin Allergy Clin Immunol, 9(4): 379-85.

Biesiekierski, J., Newnham, E., Irving, P., Barrett, J., Haines, M., Doecke, J., Shepherd,

S., Muir, J., Gibson, P. (2011). Gluten Causes Gastrointestinal Symptoms in Subjects Without Celiac Disease: A Double-Blind Randomized Placebo-Controlled Trial. Am J Gastroenterol. 106(3): 508-514.

Biesiekierski, J., Peters, S., Newnham, E., Rosella, O., Muir, J., Gibson, P. (2013). No

Effects of Gluten in Patients With Self-Reported Non-Celiac Gluten Sensitivity After Dietary Reduction of Fermentable, Poorly Absorbed, Short-Chain Carbohydrates. Gastroenterology. 145(2): 320-8.

Brottveit, M., Beitnes, AC., Tollefsen, S., Bratlie, J., Jahnsen, F., Johansen, FE., Sollid,

L., Lundin, K. (2013). Mucosal Cytokine Response After Short-Term Gluten Challenge in Celiac Disease and Non-Celiac Gluten Sensitivity. Am J Gastroenterol. 108(5): 842-50.

Bulka, C., Davis, M., Karagas, M., Ahsan, H., Argos, M. (2017). The Unintended Consequences of a Gluten-free Diet. Epidemiology. 28(3): 24-25.

Carroccio, A., Mansueto, P., Iacono, G., Soresi, M., D’Alcamo, A., Cavataio, F., Brusca,

I., Florena, A., Ambrosiano, G., Seidita, A., Pirrone, G., Rini, G. (2012). Non-Celiac Wheat Sensitivity Diagnosed by Double-Blind Placebo-Controlled Challenge: Exploring a New Clinical Entity. Am J Gastroenterol. 107(12): 1898-906.

Di Sabatino, A., Volta, U., Salvatore, C., Biancheri, P., Caio, G., De Giorgio, R., Di

Stefano, M. Corazza, G. (2015). Small Amounts of Gluten in Subjects with Suspected Nonceliac Gluten Sensitivity: A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Trial. Clin Gastroenterol Hepatol. 13(9): 1604-12.

Elli, L., Tomba, C., Branchi, F., Roncoroni, L., Lombardo, V., Bardella, M., Ferretti, F.,

Conte, D., Valiante, F., Fini, L., Forti, E., Cannizzaro, R., Maiero, S., Londoni, C., Lauri, A., Fornaciari, G., Lenoci, N., Spagnuolo, R., Basilisco, G., Somalvico, F., Borgatta, B., Leandro, G., Segato, S., Barisani, D., Morreale, G., Buscarini, E. (2016). Evidence for the Presence of Non-Celiac Gluten Sensitivity in Patients with Functional Gastrointestinal Symptoms: Results from a Multicenter Randomized Double-Blind Placebo-Controlled Gluten Challenge. Nutrients. 8(2): 84.

Mayo Clinic. (March 6, 2018). Celiac Disease. .

Mayo Clinic. (Nov 18, 2017). Irritable bowl syndrome. syndrome/symptoms-causes/syc-20360016.

McCarthy, Niall. (January 17, 2017). The Number of Americans Going Gluten Free Has

Tripled Since 2009 [Infographic].

Shahbazkhani, B., Sadeghi, A., Malekzadeh, R., Khatavi, F., Etemadi, M., Kalantri, E.,

Rostami-Nejad, M., Rostami, K. (2015). Non-Celiac Gluten Sensitivity Has Narrowed the Spectrum of Irritable Bowel Syndrome: A Double-Blind Randomized Placebo-Controlled Trial. Nutrients. 7(6): 4542-54.

Whiteman, Honor. (February 15, 2017). Gluten-free diet may have ‘unintended consequences’ for health. .

World Gastroenterology Organisation. (2016). Celiac Disease. Global Guardian of

Digestive Health. Serving the World. .

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INTEGRATIVE REVIEW OF THE EFFECT OF GLUTEN, IF ANY, ON GASTROINTESTINAL SYMPTOMS IN NON-CELIAC DISEASE PATIENTS

by

Erin A. Caplan

BA, Franklin & Marshall College, 2016

Submitted to the Graduate Faculty of

Environmental and Occupational Health

Graduate School of Public health in partial fulfillment

of the requirements for the degree of

Masters of Public Health

University of Pittsburgh

2018

UNIVERSITY OF PITTSBURGH

GRADUATE SCHOOL OF PUBLIC HEALTH

This essay is submitted

by

Erin A. Caplan

on

April 26, 2018

and approved by

Essay Advisor:

Jim (James) Peterson, PhD ______________________________

Associate Professor

Department of Environmental and Occupational Health

Graduate School of Public Health

University of Pittsburgh

Essay Reader:

Martha Ann Terry, PhD ______________________________

Associate Professor and Director, MPH Program

Department of Behavioral and Community Health Sciences

Graduate School of Public Health

University of Pittsburgh

Copyright © by Erin A. Caplan

2018

Jim (James) Peterson, PhD

INTEGRATIVE REVIEW OF THE EFFECT OF GLUTEN, IF ANY, ON GASTROINESTINAL SYMPTOMS IN NON-CELIAC DISEASE PATIENTS

Erin A. Caplan, MPH

University of Pittsburgh, 2018

Table 3 Continued

Table 3 Continued

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