Alginate as a protease inhibitor in vitro and in a model gut system; selective inhibition of pepsin but not trypsin

•Alginate inhibits proteolytic activity of pepsin but not trypsin.•Level of pepsin inhibition correlates with alginate F[M].•An in vitro model gut system was used to model alginate inhibition of proteolysis.•Proteolysis inhibited in gastric phase of digestion, but not small intestinal phase.•pH dependent ionic interactions reduce substrate availability at pH 2.5. Alginates are widely used in the food and medical industries, including as a Gastro-Oesophagul Reflux treatment. This work investigates the inhibitory effects of alginate on the reflux aggressors trypsin and pepsin and the role of alginate-substrate binding, pH and alginate structure on inhibition. Alginates were shown to reduce pepsin activity by up to 53.9% (±9.5SD) in vitro. Strong positive correlation between alginate mannuronate residue frequency and levels of pepsin inhibition was observed. Limited inhibition of trypsin was shown. Viscometric observations of pH dependent interactions between alginate and protein suggest a mechanism whereby pH dependent ionic interactions reduce substrate availability to enzyme at acidic pH. To understand how dietary protein digestion is affected by alginate, proteolytic digestion was investigated in an in vitro model of the upper digestive tract. Significant inhibition of proteolysis was shown in the gastric phase of digestion, but not the small intestinal phase.