An open-label dosing study to evaluate the safety and effects of a dietary plant-derived polysaccharide supplement on the N-glycosylation status of serum glycoproteins in healthy subjects

Abstract

Background:The functional role of dietary carbohydrates in nutrition is one of the most complex and at times controversial areas in nutritional science. In-vitro and in-vivo studies suggest that certain dietary saccharide biopolymers can have bifidogenic and or immunomodulatory effects, and that some could represent preferential substrates or precursors that can impact cellular glycosylation.Objective:Examine the impact of oral ingestion of a standardized dietary plant-derived polydisperse polysaccharide supplement (Advanced Ambrotose powder (AA)) on the N-glycosylation status of serum glycoproteins in a cohort of healthy individuals.Design:An open-label study was carried out. This study was in two phases: pilot study (n6 individuals) to assess safety and dose, and a larger study (n12) to evaluate specific glycosylation changes. Serum N-glycosylation profiles, using mass spectrometry, were monitored at weekly intervals, for 7 weeks, to evaluate baseline levels and normal fluctuations. The individuals were then monitored for a further 7 weeks, during which time increasing doses of AA were ingested (1.3-5.2 g/day).Results:No adverse events were encountered. AA supplementation resulted in distinct changes in the relative intensities of seven biantennary N-glycans (P0.001), and a significant overall shift towards increased sialylation. Regression analysis revealed a dose-dependent decrease in mono-and di-galactosylated structures (coefficient 0.130 decrease/week: P0.02 and 0.690: P0.005), and a concomitant increase in disialylated glycans (× 1.083: P0.05).Conclusions:Supplementation with the dietary plant-derived polysaccharides in AA resulted in significant changes in serum protein N-glycosylation in healthy individuals. How this occurs and whether it has biological significance remains to be evaluated. © 2011 Macmillan Publishers Limited. All rights reserved.