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

Azita Alavi (1) , Owen Fraser (1) , Edward Tarelli (1) , Martin J Bland (1) , John S Axford (1)

1 The Sir Joseph Hotung Centre for Musculoskeletal Disorders

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 / 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 (AA) on the N-glycosylation status of serum glycoproteins in a cohort of healthy individuals. Design: An open label study was used. The 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 seven weeks, to evaluate baseline levels and normal fluctuations. The individuals were then monitored for a further seven 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 disilaylated glycans (x1.083: 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.

Mots clés: Serum glycosylation; Dietary plant polysaccharides; Sialylation; Dietary fiber; Glycomodifications; N-glycans

Azita Alavi, Owen Fraser, Edward Tarelli, Martin J Bland, John S Axford. 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. European Journal of Clinical Nutrition, 2011, ⟨10.1038/ejcn.2010.263⟩. ⟨hal-00608019⟩