Evidence and hypotheses on adverse effects of the food additives carrageenan (E 407)/processed Eucheuma seaweed (E 407a) and carboxymethylcellulose (E 466) on the intestines: a scoping review

Abstract

This scoping review provides an overview of publications reporting adverse effects on the intestines of the food additives carrageenan (CGN) (E 407)/processed Eucheuma seaweed (PES) (E 407a) and carboxymethylcellulose (CMC) (E 466). It includes evidence from human, experimental mammal and in vitro research publications, and other evidence. The databases Medline, Embase, Scopus, Web of Science Core Collection, Cochrane Database of Systematic Reviews and Epistemonikos were searched without time limits, in addition to grey literature. The publications retrieved were screened against predefined criteria. From two literature searches, 2572 records were screened, of which 224 records were included, as well as 38 records from grey literature, making a total of 262 included publications, 196 on CGN and 101 on CMC. These publications were coded and analyzed in Eppi-Reviewer and data gaps presented in interactive maps. For CGN, five, 69 and 33 research publications on humans, experimental mammals and in vitro experiments were found, further separated as degraded or native (non-degraded) CGN. For CMC, three human, 20 animal and 14 in vitro research publications were obtained. The most studied adverse effects on the intestines were for both additives inflammation, the gut microbiome, including fermentation, intestinal permeability, and cancer and metabolic effects, and immune effects for CGN. Further studies should focus on native CGN, in the form and molecular weight used as food additive. For both additives, randomized controlled trials of sufficient power and with realistic dietary exposure levels of single additives, performed in persons of all ages, including potentially vulnerable groups, are needed.

Keywords:

• Autoimmune effects
• barrier function
• carboxymethylcellulose
• carrageenan
• colitis
• Crohn’s disease
• food additive
• inflammation
• inflammatory bowel disease
• intestinal microbiome
• irritable bowel syndrome
• permeability
• processed eucheuma seaweed
• scoping review
• ulcerative colitis

Acknowledgments

The authors would like to thank Ragnhild Agathe Tornes, the NIPH library, for performing the literature searches. Håkon Valen and Gunn Elisabeth Vist at NIPH, and Zak Ghouze at University College London, are thanked for good advice and help with EPPI-Reviewer. The authors gratefully acknowledge the comments of the Editor and the external reviewers selected by the Editor who were anonymous to the authors.

Declaration of interest

This research did not receive any grants from funding agencies in the public, commercial or not-for-profit sectors, and the work was funded only by regular employment and engagements of the authors at NIPH. The motivation for this work was questions to NIPH from the public about the safety of these food additives. The authors report no conflicts of interests. The authors have not participated in and do not anticipate participation in any legal, regulatory or advocacy proceedings related to the contents of the paper.