Whey Protein Digestion Releases Peptides That Stimulate Satiety Hormone CCK in Gut Cells | Research

The takeaway

Digested whey protein released low-MW peptides from β-lactoglobulin and α-lactalbumin that stimulated CCK secretion in enteroendocrine cells, with in silico prediction of ACE-inhibitory and DPP-IV-inhibitory bioactivities.

Satiety from milk protein
Small peptides released from whey protein during digestion stimulated CCK — a gut hormone that signals fullness — in enteroendocrine cells

What the researchers found

<3 kDa whey protein intestinal peptides (from β-La and α-La): strongest CCK stimulation in STC-1 cells. In silico: ACE-inhibitory, DPP-IV-inhibitory, antioxidant, antibacterial activities. ENSAEPE motif identified.

Why it matters

Understanding how food proteins release bioactive peptides during digestion enables designing functional foods that naturally regulate appetite and metabolism.

How the study worked

INFOGEST in vitro digestion, peptidomics (LC-MS/MS), STC-1 enteroendocrine cell CCK secretion assay, and MultiPep in silico bioactivity prediction.

What this study cannot tell us

In vitro digestion and cell assays. In silico predictions need experimental validation. Cannot confirm in vivo effects.

How to read the evidence

In vitro digestion + cell assay + in silico prediction. Mechanistic foundation needing in vivo validation.

When this study was published

Published in 2025.

The bigger picture

Whey protein's health benefits may be partly mediated by specific bioactive peptides released during digestion that act on gut hormone cells.

Questions still open

Would whey protein consumption measurably increase CCK and satiety in humans?
Can whey protein hydrolysates be optimized to maximize CCK-stimulating peptides?
Do the DPP-IV-inhibitory peptides survive to affect GLP-1 levels?

Common questions

Does whey protein help control appetite?

This study shows how: during digestion, whey protein releases small peptides that stimulate CCK, a satiety hormone. These peptides also have blood pressure-lowering and blood sugar-regulating properties.

Which whey proteins produce the best appetite-controlling peptides?

β-lactoglobulin and α-lactalbumin released the most CCK-stimulating peptides. Look for whey protein concentrates rich in these proteins.

Read the original research

Release of Bioactive Peptides from Whey Protein During In Vitro Digestion and Their Effect on CCK Secretion in Enteroendocrine Cells: An In Silico and In Vitro Approach.

Molecules (Basel, Switzerland), 31(2)

View on PubMed ↗Publisher’s paper ↗

Citation

Ignot-Gutiérrez, Anaís; Arellano-Castillo, Orlando; Serena-Romero, Gloricel; Alvarado-Olivarez, Mayvi; Guajardo-Flores, Daniel; Martínez, Armando J; Cruz-Huerta, Elvia. (2026). Release of Bioactive Peptides from Whey Protein During In Vitro Digestion and Their Effect on CCK Secretion in Enteroendocrine Cells: An In Silico and In Vitro Approach.. Molecules (Basel, Switzerland), 31(2). https://doi.org/10.3390/molecules31020238