Protease enzymes may enhance appetite and satiety effects of whey protein

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"P³ Hydrolyzer optimizes plant and whey protein bioavailability by enhancing the release of essential amino acids (EAAs) during the critical two-hour window following exercise known as the “anabolic window”,” explains Mark Walin, SVP of Business Development & Marketing, BIO-CAT (Getty Images)

Co-ingestion of whey protein and proteases, enzymes that breakdown proteins into peptides and amino acids, may boost the feeling of fullness and satiation in young people, says a new study.

Acute ingestion of 25 grams of whey protein concentrate (WPC) with BIO-CAT’s Optiziome P³ Hydrolyzer, a mixture of 3 microbial protease preparations, led to 14% greater levels of essential amino acids (EAA) and 15% greater levels of branched-chain amino acids (BCAA), compared to whey protein plus placebo.

Data published in The Journal of Nutrition also showed that levels of the hunger hormone ghrelin were 11% lower in the WPC plus P³ Hydrolyzer group, compared to the WPC plus placebo.

Self-reported sensations of fullness and satiation were greater during the WPC+P3 intervention, compared to WPC plus placebo.

“Although protein hydrolysates can result in an accelerated digestion and absorption rate in vivo in humans when compared with intact versions of the same protein, proteases are more versatile,” explained researchers from McGill University (Canada), University of Houston-Clear Lake (USA), BIO-CAT (USA) and Iovate Health Sciences International (Canada).

“Protease co-ingestion has the potential to enhance the digestion of any protein within a meal setting, making them applicable in a broader range of real-world dietary contexts.”

Benefits for many consumer groups

Mark Walin, senior vice president of Business Development & Marketing at BIO-CAT, told NutraIngredients that following successful results with plant protein, the company implemented this second human clinical trial to explore how Optiziome P³ Hydrolyzer may improve whey protein performance.

“Both clinical trials show that P³ Hydrolyzer optimizes plant and whey protein bioavailability by enhancing the release of essential amino acids (EAAs) during the critical two-hour window following exercise known as the “anabolic window,” he said. “As amino acids are the building blocks of muscle, this allows consumers to enhance their EAA uptake.

“P³ Hydrolyzer is designed to benefit athletes, older adults, those on a GLP-1 medication (critical to enhance EAA availability due to restricted dietary intake) and individuals recovering from illness or surgery. Multiple positive clinical results with P3 Hydrolyzer enables formulators to innovate, differentiate and vastly improve the performance of their protein products.”

Study details

The researchers first tested their hypothesis that the proteases would improve gastric release of amino acids using an in vitro model. Building on those positive results, they then conducted a randomized, double-blinded, placebo-controlled crossover study with 12 health young men and 12 healthy young women (average age of 25). The participants were randomly assigned to consume 25 grams of WPC with P³ Hydrolyzer or a maltodextrin placebo. Participants were then monitored for four hours and given an “all you can eat” meal.

Results showed higher plasma levels of EAAs and BCAAs 60 minutes after consumption of the WPC plus P³ Hydrolyzer, compared to WPC and placebo, but there were no differences between the groups for total amino acids or leucine.

Ghrelin levels were lower following ingestion of protein and proteases, while self-reported measures of fullness and satiation were higher with P3 versus placebo.

On the other hand, no differences between the groups were reported for blood sugar levels, insulin or energy intake during the “all you can eat” meal.

The researchers recommended that future studies to explore the potential metabolic effects of these observations and how this could impact whole-body and skeletal muscle protein synthesis rates. They also suggested examining how the proteases may benefit older people who have compromised protein absorption and digestion.

“In these populations, even a subtle improvement in the capacity to digest dietary protein and increase postprandial plasma amino acid availability could be of significance from a nutrition perspective,” they wrote.


Source: The Journal of Nutrition. doi: 10.1016/j.tjnut.2025.07.006. “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”. Authors: Y. Huang, et al.