Safety of proline‐specific oligopeptidase as a novel food pursuant to Regulation (EC) No 258/97

Abstract

Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on proline-specific oligopeptidase (Tolerase ® G) as a novel food ingredient submitted pursuant to Regulation (EC) No 258/97 of the European Parliament and of the Council, taking into account the comments and objections of a scientific nature raised by Member States. The novel food is an enzyme preparation of prolyl-oligopeptidase produced with a genetically modified Aspergillus niger self clone strain. The target population is the general adult population. The results from a bacterial reverse mutation test and of an in vitro chromosome aberration test did not indicate genotoxicity. The Panel considers that the reported effects observed in a 90-day rat study are treatment-related effects and can be attributed to the higher energy consumption by these animals. Taking into account the intended maximum use level for Tolerase ® G, its daily consumption would correspond to 2,746 mg TOS/person or to 39.2 mg TOS/kg body weight (bw) per day, when considering a default body weight of 70 kg for an adult person. The margin between this value and the dose in the rats, which caused effects attributable to the excess energy intake, is approximately 45. Noting this margin, the Panel considers that it is unlikely that such effects would occur in human at the intended use levels. The Panel concludes that the NF, Tolerase ® G, is safe for the intended use at the intended use level.

Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet

“…However, testing AN-PEP in patients on long-term GFD who could be exposed to real-life dietary contamination has never been investigated[ 17 - 20 ]. While important in the daily management of CeD, a “real-life” design is not devoid of limitations, as real-life variability and trial effects cannot be controlled[ 8 , 29 , 30 ].…”

“…The protease is an enzyme preparation of prolyl-oligopeptidase produced with a genetically modified A. niger strain. This enzyme’s composition and production process have been previously reported[ 19 , 20 ]. The dose of AN-PEP administered was the highest dose employed in the study König et al [ 16 ], which provides 174000 protease picomol IU/meal, where the authors demonstrated that AN-PEP significantly degraded most gluten in the stomach before it entered the duodenum.…”

Exploring substrate–microbe interactions: a metabiotic approach toward developing targeted synbiotic compositions

“…Microbial enzymes, as contained in digestive aid supplements, are prone to proteolysis in the stomach and small intestine, and therefore have a short duration of action, limiting their efficacy and user-friendliness. 128 , 129 Many microbial metabolites have an unpleasant odor or taste (e.g., short-chain fatty acids or polyamines), thus requiring odor/taste masking efforts or limiting the doses applied. An additional drawback of direct applications is the unfavorable pharmacokinetic profile upon sudden release of substances from the carrier, which is disadvantageous compared to sustained substance release or formation thereof.…”