A pilot study of N-acetyl glucosamine, a nutritional substrate for glycosaminoglycan synthesis, in paediatric chronic inflammatory bowel disease

Background: The breakdown of glycosaminoglycans is an important consequence of inflammation at mucosal surfaces, and inhibition of metalloprotease act ivity may be effective in treating chronic inflammation. Aim: To report an alternative approach, using the nutriceutical agent N-ace tyl glucosamine (GlcNAc), an amino-sugar directly incorporated into glycosa minoglycans and glycoproteins, as a substrate for tissue repair mechanisms. Methods: GlcNAc (total daily dose 3-6 g) was administered orally as adjunct therapy to 12 children with severe treatment-resistant inflammatory bowel disease (10 Crohn's disease, 2 ulcerative colitis). Seven of these children suffered from symptomatic strictures. In addition, similar doses were admi nistered rectally as sole therapy in nine children with distal ulcerative c olitis or proctitis resistant to steroids and antibiotics. Where pre- and p ost-treatment biopsies were available (nine cases), histochemical assessmen t of epithelial and matrix glycosaminoglycans and GlcNAc residues was made. Findings: Eight of the children given oral GlcNAc showed clear improvement, while four required resection. Of the children with symptomatic Crohn's st ricture, only 3 of 7 have required surgery over a mean follow-up of > 2.5 y ears, and endoscopic or radiological improvement was detected in the others . Rectal administration induced remission in two cases, clear improvement i n three and no effect in two. In all cases biopsied there was evidence of h istological improvement, and a significant increase in epithelial and lamin a propria glycosaminoglycans and intracellular GlcNAc. Conclusions: GlcNAc shows promise as an inexpensive and nontoxic treatment in chronic inflammatory bowel disease, with a mode of action which is disti nct from conventional treatments. It may have the potential to be helpful i n stricturing disease. However, controlled trials and an assessment of ente ric-release preparations are required to confirm its efficacy and establish indications for use.