Acute Effects of Oral Microbial Protease Co-ingestion with Whey Protein on Postprandial Plasma Amino Acid Concentrations, Appetite, and Satiety in Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled, Crossover Clinical Trial.

Background: Proteases are enzymes that breakdown proteins into peptides and amino acids. When co-ingested with dietary protein, proteases may enhance digestion, increase postprandial plasma amino acid concentration, and affect gut hormones, appetite, and/or satiety.

Objectives: The aim of this study was to assess the effects of a mixture of 3 microbial protease preparations (P3) on postprandial plasma amino acid concentration when co-ingested with whey protein concentrate (WPC) in healthy young adults.

Methods: P3 was first tested in vitro for proteolytic effects in a static simulation of orogastric digestion. In a subsequent randomized, double-blinded, placebo-controlled crossover study, 12 males and 12 females [body mass index (BMI)-mean: 23.6 (SD: 2.9); age-mean: 25 y (SD: 3 y)] consumed WPC (25 g protein) containing P3 or placebo (maltodextrin). Plasma amino acid, glucose, insulin, and appetite regulatory hormone concentrations were assessed at baseline and throughout a 240-min postprandial period. Perceived appetite sensations were assessed by visual analog scale questionnaires. An ad libitum meal was administered following each treatment to determine energy intake.

Results: P3 demonstrated proteolytic activity at 50,000 hemoglobin units on tyrosine basis per 31.9 g serving of WPC in vitro. Adjusted geometric mean postprandial plasma 60-min incremental area under the curve was 14% greater for essential amino acids (treatment: P = 0.025) and 15% greater for branched-chain amino acids (treatment: P = 0.021) with P3 than placebo, with no differences for total amino acids or leucine (all P > 0.05). Adjusted geometric mean postprandial plasma ghrelin was 12% lower (treatment: P < 0.001), whereas adjusted mean visual analog scale-derived fullness (treatment: P = 0.025) and satiation (interaction: t = 30-150 min; all P < 0.05) were greater with P3 than placebo. Adjusted mean postprandial plasma glucose, insulin, and ad libitum meal energy intake were not different between treatments (all P > 0.05).

Conclusions: Co-ingestion of WPC with P3 can enhance early postprandial plasma aminoacidemia and alter select indices of appetite and satiety in young adults. This trial was prospectively registered at clinicaltrials.gov as NCT05957185.