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.

Sidney Abou Sawan, José A Correa, Kelly M Tinker, Sean M Garvey, Sarkis J Hannaian, José A Morais, Zachary W Bell, Tyler A Churchward-Venne, Yijia Huang, Alyasamin Alhamwi, Benjamin Sauvageau, Divine Malenda, Silar Gardy, Thalia Krauth-Ibarz, Ari Gritsas

Journal: The Journal of nutrition 2025

PMID: 40675336

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Plain Language Summary

Protein is a nutrient that is essential for growth and development. After consumption, protein digestion is partly performed by digestive enzymes called proteases resulting in the release of amino acids, which are the building blocks for muscle. They are also responsible for the release of metabolites which trigger hormones involved in the control of food consumption. This study investigated the effects of a specific enzyme, called microbial protease, alongside whey protein, on the production of amino acids.

The findings showed that the co-ingestion of microbial protease with whey protein significantly influenced the levels of amino acids in the blood after eating, as well as affecting appetite and satiety (the feeling of being full). There were no effects on blood glucose levels, insulin levels and the amount eaten.

It was concluded that the addition of microbial protease to a protein source is associated with increased amino acid release and feelings of being full. This study could be used by healthcare professionals to understand how microbial protease may enhance the effects of protein digestion on amino acid levels and appetite control.

Abstract

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.

Address: Department of Kinesiology and Physical Education, McGill University, Montréal, Quebec, Canada.; Department of Kinesiology and Physical Education, McGill University, Montréal, Quebec, Canada; Department of Clinical Health and Applied Sciences, University of Houston-Clear Lake, Houston, TX, United States.; Department of Kinesiology and Physical Education, McGill University, Montréal, Quebec, Canada; Research Institute of the McGill University Health Centre, Montréal, Quebec, Canada.; Department of Mathematics and Statistics, McGill University, Montréal, Quebec, Canada.; Research Institute of the McGill University Health Centre, Montréal, Quebec, Canada.; Department of Research and Development, BIO-CAT, Inc, Troy, VA, United States.; Iovate Health Sciences International, Oakville, Ontario, Canada.; Research Institute of the McGill University Health Centre, Montréal, Quebec, Canada; Division of Geriatric Medicine, McGill University, Montréal, Quebec, Canada.; Department of Kinesiology and Physical Education, McGill University, Montréal, Quebec, Canada; Research Institute of the McGill University Health Centre, Montréal, Quebec, Canada; Division of Geriatric Medicine, McGill University, Montréal, Quebec, Canada. Electronic address: [email protected].

DOI: 10.1016/j.tjnut.2025.07.006