Experts Confirm: Alternative Enzyme Therapies for Celiac Disease Unfounded
“Enzyme supplements marketed as digestive support for a gluten-free life style with highly suggestive brand names could easily entice patients to try these supplements to counteract the deleterious effects of (inadvertent) gluten consumption,” concludes a study published 2015 Jun 1. doi: 10.1371/journal.pone.0128065.
George Janssen, Chantal Christis, Yvonne Kooy-Winkelaar, Luppo Edens, Drew Smith, Peter van Veelen and Frits Koning asserted, “that available digestive enzyme supplements are ineffective in degrading immunogenic gluten epitopes.”
Here we investigated the composition of such enzyme supplements and tested their ability to degrade gluten proteins and immunogenic fragments thereof. We observed that the enzyme preparations indeed contain proteolytic activity but that the major constituents of the preparations are amylases. We observed that the pH optimum of the principal proteolytic activity in the enzyme supplements is between pH 6.0 and 8.0 and thus outside the pH range of the stomach.
Moreover, we found that the proteolytic activity of the preparations could only partly neutralize gluten proteins as determined by ELISA. In this respect it is important that while the R5 ELISA used is approved by the Codex Alimentarius Commission for determining gluten content in foods, it is specific for a peptide sequence (QQPFP) that is not present in the immunodominant sequences from α-gliadins but is present in a number of γ-gliadin sequences.
Thus, the observed reduction in gluten content with the enzyme supplements as determined with the R5 ELISA is not likely to reflect an actual breakdown of all immunogenic sequences. This is corroborated by mass spectrometric analyses of gluten degradation products which indicates that the commercial enzyme supplements were completely ineffective in degrading immunogenic gluten fragments from both the α- and γ-gliadins. We would like to stress that we have tested the enzyme supplements under a variety of pH conditions and that we have used state of the art mass spectrometry to follow the degradation of well characterized immunogenic α- and γ-gliadin fragments. These 33-mer and 26-mer fragments have been shown to arise from gastrointestinal degradation of gliadin proteins [4,22]. It is well established that the 33-mer fragment contains six copies of immunodominant gluten peptides to which T cell responses are almost invariably found in HLA-DQ2 positive patients. Similarly, the 26-mer fragment contains three immunogenic peptides. Mass spectrometry is a very sensitive technique that allows highly accurate and sensitive detection and identification of peptides and degradation products thereof.
Our results unequivocally demonstrate that the enzyme supplements are only capable of removing a few N-terminal amino acids from both the 33- en 26-mer gliadin fragments, leaving the nine immunogenic epitopes intact. Only at an elevated dose of 10 capsule equivalents we observed that a single epitope of the 26-mer was partially degraded. Thus, the currently available enzyme supplements cannot be used to counteract the effect of gluten consumption in gluten intolerant individuals. Importantly, this implies that all enzyme preparations with a similar composition will fail to effectively degrade gluten.
Finally, next to CD, there is presently much attention for so-called non-celiac gluten sensitivity. Although this is at present an ill-defined disease entity, it has led to the notion that gluten containing cereals pose a general risk to health. Evidently, our observation that the commercial enzyme supplements tested here do not degrade gluten indicates that they would neither be beneficial in this type of disorder. A lifelong gluten-free diet is currently the only available treatment for gluten intolerant individuals.”
*NOTE from The Celiac Scene: At the International Celiac Disease Symposium that The Celiac Scene attended in Chicago in 2013, Dr. Stefano Guandalini, Professor of Pediatrics, Section Chief, Pediatric Gastroenterology, Hepatology, and Nutrition and Founder and Medical Director, University of Chicago Celiac Disease Center specifically debunked the popular myth that over the counter products containing dipeptidyl peptidase-4 or DPP-IV – the active ingredient in Gluten Ease, Gluten Cutter, Gluten Aid, Gluten Relief – can break down gluten:
“Totally unjustified by the lack of any evidence that they can in fact digest and detoxify gluten. It is an enzyme. It helps to digest protein in general. It has no activity toward gluten. Our intestines have plenty of DPP-IV.“
He finished by saying, “Save your money!”
Canadian Celiac Association Weighs in on Alternative Therapies
by Sue Newell, Operations Manager, Canadian Celiac Association as published in the CCA eNews August 2015
“It would have been hard to miss the news from the University of Alberta over the last few weeks. Scientists find enzymes that break down gluten so celiacs can eat pizza and beer! If you just read the brief news reports, it all sounded great. It would be great if it was true. Right now, it is a “good idea, hope it works, looking forward to hearing the results of your trials a few years from now.” Unfortunately, that doesn’t make good headlines.
There are a number of potential drugs in the formal drug testing pipeline to add to the current treatment for celiac disease. Some CCA members have already taken part in the trials. There are many more ideas floating around that theoretically have a good chance of working. None of them are on the market yet and all need more rounds of formal testing before they could ever be approved by Health Canada.
There is one type of product on the market right now. Gluten Ease, Gluten Cutter, Gluten Aid, Gluten Relief*; all the names sound so promising. The only problem is they don’t make gluten safe for someone with celiac disease or gluten sensitivity. When you read the literature on the products, they clearly say “These statements have not been evaluated by the Food and Drug Administration”. In other words, “we have not had to prove that the pills do what we say they do.”
When there are treatments to augment the gluten-free diet, you will hear about it from the CCA [and The Celiac Scene], not from the popular press. There might even be options that will replace the gluten-free diet as a treatment, but that is a very long way down the road from now. In the mean time, we are lucky to have an amazingly effective treatment that allows us to actually get better.”
