Gluten is a tough plant protein to digest. Our bodies release a variety of different enzymes to “chop up” or break down proteins in our stomach but they cannot break down gluten. Long chains of undigested gluten protein leave the stomach and reach the small intestine. While most people can handle these undigested gluten protein chains, those with celiac disease cannot. Researchers are actively searching for an enzyme that can quickly break down the small amounts of gluten before it leaves the stomach – this would offer those with gluten related disorders some extra protection.

One important point here is that it does NOT replace the gluten-free diet. Enzymes on the market offer a false sense of security because people who use enzymes might believe they can be less careful with their diet. This can lead to harmful consequences in the long term. There’s no good evidence that the enzymes currently on the market (GliadinX, Gluten Digest, Gluten Rid, Gluten Cutter and others*) can protect people with celiac disease from even small amounts of gluten. Researchers are optimistic, though, that finding the correct enzyme and formulation could be quite useful for those with celiac disease – stay tuned for the research.

Preliminary data for AN-PEP (Aspergillus Niger prolyl endoprotease), the specific enzyme used in GliadinX and others, seems promising per its researchers. Researchers of AN-PEP have shown that the enzyme is safe and well tolerated in healthy human subjects. They also report that the amount of gluten reaching the duodenum (first part of small intestine) was significantly reduced with AN-PEP.¹ However, they are quite cautious.

“The AN-PEP enzyme has been developed as a dietary supplement that in conjunction with a gluten-free diet may help subjects intolerant to gluten to digest unintended dietary gluten. Despite these promising results, the data does not prove that AN-PEP allows subjects intolerant to gluten to ingest gluten safely.”¹

In the first randomized double-blind placebo-controlled pilot-study evaluating the safety and efficacy of AN-PEP in celiac disease, researchers  concluded that a larger number of study subjects and a longer gluten challenge seems to be required to cause significant clinical changes and to determine whether the tendency of AN-PEP to reduce IgA-tTG deposits in the small intestine is of clinical significance.²

First Bottom line:

Before AN-PEP can be used as a future digestive aid for subjects intolerant to gluten, results must be confirmed and AN-PEP’s efficacy and safety evaluated in human studies of subjects intolerant to gluten. ¹ More research is needed. The life-long gluten-free diet remains the only currently available and acceptable treatment for celiac disease.

There is a second consideration for those with gluten-related disorders interested in using digestive enzymes of any kind. While there is no evidence-based clinical research to support the use of enzymes in celiac disease, some people have found relief from trialing digestive enzymes to help with symptoms, such as gas and bloating, related to poor digestion in general. Unlike medications which are chemically synthesized in a factory, enzymes must be produced by a living organism, such as yeast or bacteria. Tricia Thompson, Luke Emerson and I wrote an article on probiotics and digestive enzymes that I discuss below.

“Bacteria, mold, yeast, and enzymes produced by bacteria are used in a variety of products, including probiotics and digestive enzymes. These microorganisms may be grown on media that may include ingredients derived from gluten-containing grain (i.e., wheat, barley, and rye). There is some concern that the use of gluten-derived/gluten-containing growth media may result in residual gluten protein fragments remaining in products containing microorganisms such as bacteria and mold.”³

When we read the label of a digestive enzyme, we can see the bacterial or mold strain listed but the label does not typically include the type of growth media used. We need the US Food and Drug Administration (FDA) to provide more guidance on labeling these proteins.

In June 2016, Gluten Free Watchdog, LLC, a gluten test reporting service in Manchester, MA,  tested a labeled gluten-free probiotic that had been accidentally grown on spent brewer’s yeast The results showed 283.5 ppm of gluten (<20ppm is considered gluten-free). When it was tested again in July and November 2016 using molasses, the results were <10ppm.³

Digestive enzymes and probiotics labeled gluten-free must comply with FDA’s gluten-free labeling rule and contain < 20 ppm gluten. The FDA has issued a rule for gluten-free labeling of fermented or hydrolyzed foods - this includes digestive enzymes and probiotics. However, the specifics on how products containing bacteria and mold cultivated on wheat, barley or rye will be regulated for compliance is not clear.³ Please read the article below about our suggestions to suppliers and manufacturers regarding the specific type of testing for gluten that is recommended, the Competitive ELISA. We also include a list of questions at the end of the article that consumers can ask a digestive enzyme or probiotic company if they choose to use these products.

Second Bottom line:

Make sure the product is labeled gluten-free. And “until more is known about residual gluten from growth media, erring on the side of caution and avoiding products containing ingredients grown on gluten-containing growth media may be best if the product is not tested for residual gluten using a competitive ELISA.”³

*This list of digestive enzyme supplements is not comprehensive.

1. Salden, et al. Randomised clinical study: aspergillus niger-derived enzyme digests gluten in the stomach of healthy volunteers. Aliment Pharmacol Ther. 2015 Aug;42(3):273-85.
2. Greetje, JT. Consumption of gluten with gluten-degrading enzyme by celiac patients: A pilot-study. World J Gastroenterol. 2013 Sep 21; 19(35): 5837–5847.
3. Thompson T, Dennis M, Emerson L. Gluten-free labeling: are growth media containing wheat, barley, and rye falling through the cracks? J Acad Nutr Diet. 2017 Sep 1.
4. A summary of the Thompson, Dennis, Emerson article 

Reviewed September 26, 2022.