Evaluation of Safety and Efficacy of Dietary Supplement ZyGluten In Patients with Gluten Sensitivity

Celiac.com 07/05/2016 - Principal Investigator: Amrit P.S. Narula M.D, F.A.C.P, F.A.C.G, F.A.C.N., A.G.A.F
Study Coordinator: Alicia Mercuri, PA-C

Background
Research estimates that approximately 18 million Americans have gluten sensitivity. That is six times more than patients confirmed with celiac disease. Non-celiac gluten sensitivity is defined as those individuals who cannot tolerate gluten in the diet and experience the same symptoms attributed to celiac disease, but lack antibodies and intestinal damage as seen in celiac disease.

Celiac.com Sponsor (A12):
A dietary supplement called ZyGluten was developed from in vitro studies, not in vivo. The primary aim in its development was a supplement which, if taken at the beginning of a meal, would hydrolyze gluten concentration in ingested food. Foods tested included McDonald's hamburger, white sliced bread, a plain bagel, macaroni and cheese, spaghetti, a muffin, and frozen pizza. The amount of gluten was measured at 0, 30 and 60 minutes after the introduction of ZyGluten. In all samples, gluten measured at the end of 60 minutes was less than 20 ppm.

ZyGluten is a compound of amylases, proteases, and lipase enzymes with probiotics, specifically Lactococcus lactis and Lactococcus cremoris. It is derived from plant and microbial sources.

Inclusion Criteria

• Ages 18-80 years
• Physician diagnosed gluten sensitivity by history and experienced symptoms of gluten sensitivity for at least 1 month prior to involvement
• Willing to take supplement twice daily for 2 weeks
• Sign informed consent

Exclusion criteria

• Active Inflammatory Disease
• Celiac disease confirmed by antibodies and duodenal biopsy
• Peptic ulcer disease
• Lactose intolerance
• Pregnant or lactating women
• Received any experimental drug within 30 days of enrollment

Methods
27 patients, all of whom met the inclusion criteria, were selected to take 2 capsules of ZyGlutens before 2 major meals of the day for 2 weeks. 23 patients were female and 4 were male, with ages ranging from 25-77. The following symptoms were assessed at baseline, week 1, and week 2 which was the conclusion of the study:

• Abdominal pain
• Diarrhea
• Constipation
• Headaches
• Joint pain
• Fatigue
• The severity of symptoms was measured as mild, moderate, or severe, and none if symptoms were absent.

All patients were contacted by phone within 48 hours of start of the trial to assess for any adverse effects. Following parameters were checked at baseline, week 1, and week 2:

• Weight
• Height
• Blood pressure
• Pulse rate
• Respiration rate
• Patients were not charged or reimbursed for their participation in the study.

Results
The following number of patients (27) had these symptoms at baseline:

 The following number of patients (23) had these symptoms at week 1:

The following number of patients (23) had these symptoms at week 2: 

The following number of patients rated their symptom improvement as:

• No improvement: 0
• Improved: 4
• Markedly improved: 19

Adverse Effects
No patients reported any adverse effects.

Participants
Twenty-seven participants were enrolled in the study. Two patients withdrew from the study; one of which had a scheduling conflict with follow-up visits and one stopped taking the medication due to increased sleepiness after two pills. Two patients were lost to follow-up. These four patients were excluded from analysis.

Conclusion
In conclusion, ZyGluten study is a 2 week open labeled trial. Our outcome so far has shown to be extremely efficacious with no significant side effects. There was no significant difference found in patients who complained of headaches or joint pain. The majority of the patients found significant improvement in their symptoms of abdominal pain, bloating, changes in bowel habits, and fatigue. In fact, 83% of patients rated that their symptoms markedly improved, and 17% rated an improvement in their symptoms.

Patient Testimonials

• *The medication was known by patients as ‘Gluten Buster' during the clinical trial.
• "Medication has given me more freedom. I am no longer afraid to eat, especially away from home. I am very pleased with the medication".-MF
• "My symptoms have improved. I would like to keep taking this if I can, especially since it's natural, to see how long I can go without an endoscopy".-MH
• "I feel that this pill has made a tremendous improvement in my condition". –BW
• "Bloating is gone. Stools seem to be more formed. Feeling good". –PS
• "It's wonderful to not be limited in what I can eat. It's great not to have the symptoms of pain, etc. when eating gluten foods". –JH
• "Great for bloating".-JF
• "Very little of passing gas. I feel good". -PW
• "Bloating is a lot better". -LW
• "I have not had any cramping or urgency to have a BM after a meal. My bowel movements are now normal. I have had no GI distress since on the meds". –KY
• "Gluten Buster has been a miracle pill. After so many years of having bowel problems, I never knew what it was like to have a regular bowel movement. I have had no problems with digestive system since I starting taking these pills". -JM
• "Medication was very helpful". –KO
• "My experience with the Gluten Buster that Dr. Narula has given me to take has been simply amazing. It has made my quality of life so much better. He is an amazing doctor to help those that otherwise thought there was no hope! I feel great"!-CM
• "Seems a little bit better. Still have IBS. Still have a lot of gas and bloating."-AM
• "It has been helping to go to the bathroom. The weight is going up and the stomach is going down a little bit".-SH
• "Before taking the medicine, mornings were hard because of bloating and diarrhea. Now I feel great in the morning".-GK
• "Gluten Buster is a life changer. Will definitely go on it when available in market." -MC
• "It is helping with bloating and gas. Has improved all of my GI symptoms. Overall, I can eat anything, including French fries and food I could not eat before (Super Pill)". -MK
• "I feel it has improved. Still have bloating, but eating regular food. Diarrhea has improved, no pain in stomach or abdomen". -BS
• "I feel 10x better than I did before starting the medication. No stomach cramps of bloating, I only have a BM twice/day. Feel great!" -JB
• "I am doing 100% better now since I have been taking the Gluten Buster meds". - JZ
• "Passing more gas, feeling better". -ML
• "I'm feeling better. I'm eating anything I want, not sticking with gluten free food. If it's due to taking the Gluten Buster, then I would still take it". -BS
• "It has made a big difference in bloating and abdominal pain. I would like to continue taking it". -JP
• "My stomach feels fantastic when I take the product. This should be available for all people with gluten sensitivity. This would be a great idea for Shark Tank. It needs to be available to the masses! I don't know how my stomach will survive without it, especially at the holidays". -LT

References

1. Am J Gastroenterol. 2011 Mar;106(3):508-14; quiz 515. doi: 10.1038/ajg.2010.487. Epub 2011 Jan 11. Gluten causes gastrointestinal symptoms in subjects without celiac disease: a double-blind randomized placebo-controlled trial. Biesiekierski JR1, Newnham ED, Irving PM, Barrett JS, Haines M, Doecke JD, Shepherd SJ, Muir JG, Gibson PR.
2. The Oslo definitions for celiac disease and related terms. Jonas F Ludvigsson,1,2 Daniel A Leffler,3 Julio C Bai,4 Federico Biagi,5 Alessio Fasano,6 Peter H R Green,7 Marios Hadjivassiliou,8 Katri Kaukinen,9 Ciaran P Kelly,3 Jonathan N Leonard,10 Knut Erik Aslaksen Lundin,11 Joseph A Murray,12 David S Sanders,13,14 Marjorie M Walker,14 Fabiana Zingone,15 Carolina Ciacci16
3. Food Allergy - An Overview (PDF|1 MB). DHHS. NIH. National Institute of Allergy and Infectious Diseases.
4. Gastroenterol Hepatol. 2014 Jun-Jul;37(6):362-71. doi: 10.1016/j.gastrohep.2014.01.005. Epub 2014 Mar 22. [Non-celiac gluten sensitivity: a critical review of current evidence]. [Article in Spanish] Molina-Infante J1, Santolaria S2, Montoro M2, Esteve M3, Fernández-Bañares F3.
5. Gluten Causes Gastrointestinal Symptoms in Subjects Without Celiac Disease: A Double-Blind Randomized Placebo-Controlled Trial. Jessica R Biesiekierski, Evan D Newnham, Peter M Irving, Jacqueline S Barrett, Melissa Haines, James D Doecke, Susan J Shepherd, Jane G Muir and Peter R Gibson.
6. Nutrients. 2013 Sep 26;5(10):3839-53. doi: 10.3390/nu5103839. Non-Celiac Gluten sensitivity: the new frontier of gluten related disorders. Catassi C1, Bai JC, Bonaz B, Bouma G, Calabrò A, Carroccio A, Castillejo G, Ciacci C, Cristofori F, Dolinsek J, Francavilla R, Elli L, Green P, Holtmeier W, Koehler P, Koletzko S, Meinhold C, Sanders D, Schumann M, Schuppan D, Ullrich R, Vécsei A, Volta U, Zevallos V, Sapone A, Fasano A.
7. BMC Med. 2014 May 23;12:86. doi: 10.1186/1741-7015-12-86. Non-celiac gluten sensitivity - why worry? Lundin KE.
8. BMC Med. 2014 May 23;12:85. doi: 10.1186/1741-7015-12-85. An Italian prospective multicenter survey on patients suspected of having non-celiac gluten sensitivity. Volta U1, Bardella MT, Calabrò
9. Neurogastroenterol Motil. 2013 Nov;25(11):864-71. doi: 10.1111/nmo.12216. Epub 2013 Aug 12. Non-celiac gluten sensitivity: clinical relevance and recommendations for future research. Mooney PD1, Aziz I, Sanders DS.
10. World J Gastroenterol. 2014 Jul 21;20(27):8837-45. doi: 10.3748/wjg.v20.i27.8837. Irritable bowel syndrome and food interaction. Cuomo R, Andreozzi P, Zito FP, Passananti V, De Carlo G, Sarnelli G.
11. Expert Rev Gastroenterol Hepatol. 2012;6(1):43-55. Problems of an Emerging Condition Separate From Celiac Disease. Amy C Brown
12. Dig Dis Sci. 1999 Jul;44(7):1317-21. Pancreatic supplements reduce symptomatic response of healthy subjects to a high fat meal. Suarez F1, Levitt MD, Adshead J, Barkin JS.