New Research: Digestive Enzymes for NCGS

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Therapy for Non Celiac Gluten Sensitivity (NCGS) recommends complete elimination of gluten from the diet. A recent study by Scricciolo et al. investigated whether novel enzymes, designed to help metabolize gluten, can support reintroduction of gluten without triggering symptoms.

NCGS is characterized by intestinal and extraintestinal symptoms that occur after ingestion of foods containing gluten in patients in whom both celiac disease and wheat allergy have been ruled out.

Currently, the only treatment available for NCGS is a gluten-free diet and no accompanying or secondary conditions have been associated with NCGS. Patients with NCGS may follow a less-strict diet than those with celiac disease and may not follow it lifelong. While symptoms may disappear after a patient implements a gluten-free diet, it is unclear to what extent they may tolerate reintroduction of gluten.

Various digestive enzyme supplements claim to help break down gluten. These enzymes designed to help metabolize gluten could theoretically represent a therapeutic option for NCGS patients to allow for diet liberalization. The study by Scricciolo et al. aims to evaluate the effect of controlled reintroduction of gluten on gastrointestinal symptoms in NCGS patients taking the proline-specific endopeptidase enzyme P1016.


In this randomized, double-blind, placebo-controlled, single-center study, gluten was gradually reintroduced over a period of three consecutive weeks.

Twenty-eight adult patients with NCGS who had been on a gluten-free diet for at least six months were included. Participants were randomly divided into two groups and received either the proline-specific endopeptidase enzyme P1016 or a placebo.

In both groups, gluten was reintroduced at an increasing dose. All participants were assessed for symptoms, quality of life, and mental health symptoms before the start of the study, at the end of the first week, at the end of the second week, and at the end of the third week of the intervention.


After the intervention phase, 11 patients in the placebo group and 12 patients in the P1016 group completed the protocol and were included in the analysis. Results showed no significant differences after gluten reintroduction between the two groups.

No effect of P1016 on the symptoms was found. Patients in both groups reported a significant increase in abdominal pain and deterioration in stool consistency. In addition, there were no differences during the intervention, either within or between groups, by SCL-90 values ​​(general score) or SF-36 values ​​(physical health)


The study was designed to test the hypothesis that consumption of the proline-specific endopeptidase P1016 leads to an improvement in symptomatic and psychological quality of life in NCGS patients who receive controlled amounts of gluten. However, the results of the study showed no differences in terms of gastrointestinal and psychological symptoms or quality of life. The results therefore do not support the effectiveness of the proline-specific endopeptidase P1016 as a digestive enzyme supplement for those with NCGS.

Despite its potential impact on quality of life, the only effective treatment for patients with NCGS remains a gluten-free diet. While all patients show symptom improvement on a gluten-free diet, the degree of gluten restriction needed to achieve relief may vary from patient to patient.

Looking forward, future research could investigate the use of a proline-specific endopeptidase enzyme along with probiotics or prebiotics to assess the effect of controlled reintroduction of gluten on gastrointestinal symptoms in patients with NCGS.