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

• Published in: European journal of clinical nutrition Vol. 65; no. 5; pp. 648 - 656
• Main Authors: Alavi, A, Fraser, O, Tarelli, E, Bland, M, Axford, J
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2011; Nature Publishing Group
• Subjects: 631/45/72/1201; 631/92/436; 692/700/459/1994; Adult; Biological and medical sciences; Biopolymers; blood proteins; blood serum; Carbohydrates; Clinical Nutrition; dietary carbohydrate; Dietary Carbohydrates - administration & dosage; Dietary fiber; Dietary supplements; Dietary Supplements - adverse effects; dose response; Dose-Response Relationship, Drug; Epidemiology; Feeding. Feeding behavior; Female; Flowers & plants; Fluctuations; Food safety; Fundamental and applied biological sciences. Psychology; Glycoproteins; Glycoproteins - blood; Glycosylation; Health aspects; Humans; immunomodulators; Ingestion; Internal Medicine; Male; Mass spectrometry; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Middle Aged; Nutrition research; Original; original-article; Physiological aspects; Pilot Projects; Plants - chemistry; Polysaccharides; Polysaccharides - administration & dosage; Polysaccharides - blood; Public Health; Regression analysis; Saccharides; Safety; Vertebrates: anatomy and physiology, studies on body, several organs or systems; United Kingdom; Serum glycosylation; sialylation; glycans; dietary fiber; dietary plant polysaccharides; glycomodifications; Healthy subject; Toxicity; Glycoprotein; Label; Metabolic diseases; Glycosylation; N-glycans; Posology; Feeding; Plant; Diet; Serum; Supplementation; Dietary fiber; Polysaccharide; Food supplement; Dietary plant polysaccharides; Glycomodifications; Sialylation
• ISSN: 0954-3007; 1476-5640; 1476-5640
• DOI: 10.1038/ejcn.2010.263

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.