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

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 (n=6 individuals) to assess safety and dose, and a larger study (n=12) 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 (P<0.001), 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: P=0.02 and −0.690: P=0.005), and a concomitant increase in disialylated glycans ( × 1.083: P<0.05). 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.