Combination of Gluten-Digesting Enzymes Improved Symptoms of Non-Celiac Gluten Sensitivity: A Randomized Single-blind, Placebo-controlled Crossover Study

Abstract

IntroductionRecently, the population of individuals with non-celiac gluten sensitivity (NCGS) who do not have celiac disease but show improved symptoms with a gluten-free diet, has increased. Enzyme replacement therapy using digestive enzymes is expected to improve the symptoms of NCGS and be sustainable, since gluten-related proteins that are indigestible by the digestive system have been considered triggers of NCGS.MethodsWe selected patients with NCGS by screening demographic interviews, as well as performing medical evaluations, anti-gluten antibody tests, and gluten challenge tests. We performed a single-blind and crossover clinical trial with these subjects using a gluten challenge with the enzyme mixture or a placebo. Our designed enzyme mixture contained peptidase, semi alkaline protease, deuterolysin, and cysteine protease derived from Aspergillus oryzae, Aspergillus melleus, Penicillium citrinum, and Carica papaya L., respectively.ResultsAdministration of the enzyme mixture significantly decreased the change in the score of the symptom questionnaire before and after the gluten challenge compared with administration of the placebo in patients with NCGS without adverse events. In particular, the changes in the score of the gluten-induced incomplete evacuation feeling and headaches were significantly improved. The serum levels of interleukin (IL)-8, tumor necrosis factor (TNF)-α, andregulated on activation, normal T cell expressed and secreted (RANTES) in subjects were not significantly changed by gluten, as expected from previous studies, and the enzyme mixture did not affect these inflammatory markers.ConclusionIn this human clinical study, we demonstrated the efficacy of the enzyme mixture derived from microorganisms and papaya in improving the symptoms of NCGS.

More fuel to the fire: some patients with non-celiac self-reported wheat sensitivity exhibit adaptive immunological responses in duodenal mucosa

“…The inflammatory response was conspicuously higher in CD subjects although pro-inflammatory cytokine-expressing cells were also evident in NCSRWS patients, except for IL-6-and IL-8-expressing cells. These findings have been previously reported by other studies that evaluated cytokine levels on serum and peripheral blood mononuclear cells or duodenal mucosa culture supernatants by ELISA [32][33][34][35][36].…”

More fuel to the fire: Some patients with non-celiac self-reported wheat sensitivity exhibit adaptive immunological responses in duodenal mucosa.

“…The in ammatory response was conspicuously higher in CD subjects although pro-in ammatory cytokine-expressing cells were also evident in NCSRWS patients, except for IL-6-and IL-8-expressing cells. These ndings have been previously reported by other studies that evaluated cytokine levels on serum and peripheral blood mononuclear cells or duodenal mucosa culture supernatants by ELISA (32)(33)(34)(35)(36).…”

Protein Digestibility of Cereal Products

“…Several researchers have been trying to develop solutions for people suffering from celiac disease. One of these investigated solutions involves the pretreatment of the gluten protein with peptidase mixtures (e.g., papaya non-specific endopeptidase and three microbial peptidases ( Aspergillus oryzae leucine aminopeptidase, Aspergillus melleus endopeptidase with activity against hydrophibic amino acid residues and Penicillium citrinum deutorlysin)) [84]. These peptidases are able to digest the above proline-rich peptides and, hence lower the concentration of the immunogenic peptides.…”