Preparatory work for the safety evaluation by EFSA of Human‐identical Milk Oligosaccharides as Novel Foods

This report describes a scoping literature review as preparatory work for the safety evaluation by EFSA of Human‐identical Milk Oligosaccharides (HiMOs) as Novel Foods (NFs). The main objective was to gather information on the concentrations of Human Milk Oligosaccharides (HMOs) in human milk, both individual and total, and the combinations/mixtures of HiMOs/HMOs in commercially available products or those reported in the literature.

A scoping literature review was conducted, including a search strategy implemented in biomedical (PubMed) and multidisciplinary (Web of Science) databases from 2013 to March 2024, supplemented by an ad hoc search for primary studies included in two key recent systematic reviews and grey literature searches on relevant food business operators' websites. Both primary and secondary studies were selected to determine the individual concentrations of target HMOs, the total concentration of HMOs and relevant HMO fractions, and the combinations/mixtures of HiMOs/HMOs. Only studies with full text published in English or Spanish were eligible, excluding patents, editorials, conference abstracts, books, and dissertations.

The structured searches yielded 2,851 unique references, with 218 selected for full‐text evaluation and 36 additional unique references from the key systematic reviews. Ultimately, 171 publications were included in the review. Fourteen companies related to HiMOs were identified through grey literature. In most publications, concentration data for multiple groups of donors (e.g., based on factors like secretor status or lactation period) were reported. By groups of donors, the mean total concentration of HMOs in milk (excluding colostrum) was 6,740 mg/L, whereas the mean by publication was 5,341 mg/L. By publication, the mean concentrations of individual HMOs (mg/L, excluding colostrum) were: LNnT 288, LNT 971, 2'‐FL 1,468, 3‐FL 800, DFL 232, 3'‐SL 212, 6'‐SL 365, LNFP I 738, and LNT/LNnT 611. By groups of donors, the mean concentrations (mg/L, excluding colostrum) were: LNnT 382, LNT 1064.1, 2'‐FL 1685, 3‐FL 907, DFL 303, 3'‐SL 225, 6'‐SL 435, LNFP I 773, and LNT/LNnT 882. By publication, the mean concentration (mg/L) of groups of HMOs mean concentrations (excluding colostrum) was: 4,577 for total neutral; 851 for total acidic; 4,635 for total acidic fucosylated; 1,631 for α‐1‐3/4‐fucosylated; 3,304 for α‐1‐2‐fucosylated; 1,601 for non‐fucosylated; 1,505 for total sialyllated; 2,293 for acidic sialyllated. By group of donors, the mean concentration (mg/L) of groups of HMOs mean concentrations (excluding colostrum) was: 3,942 for total neutral; 1,032 for total acidic; 6,477 for total acidic fucosylated; 1,650 for α‐1‐3/4‐fucosylated; 3,748 for α‐1‐2‐fucosylated; 2,026 for non‐fucosylated; 1,957 for total sialyllated; 2,293 for acidic sialyllated. The most frequent combinations of HMOs/HiMOs were LNnT + 2'‐FL (24 products, 32%) and 2'‐FL + 3'‐SL (12 products, 16%).

The findings of this review will support EFSA in the safety evaluation of HiMOs as NFs, in accordance with the EC mandate (M‐2023‐00157).