A New Form of Collagen Peptide Found in Blood After Taking Collagen Supplements
Researchers discovered a previously unknown cyclic collagen peptide in human blood after taking collagen supplements, and it stimulated skin cell growth better than the known linear form.
Quick Facts
What This Study Found
A novel cyclic form of the collagen peptide Pro-Hyp was detected in human blood for the first time after ingestion of collagen hydrolysate. Cyclic Pro-Hyp peaked in plasma at 2 hours post-ingestion, reaching levels of 0.14–0.34 nmol/mL — approximately 5% of the linear Pro-Hyp concentration.
In cell culture experiments, cyclic Pro-Hyp at 7 nmol/mL significantly enhanced the growth rate of mouse skin fibroblasts on collagen gel more than the linear form, suggesting it may be more biologically active despite its lower concentration.
Key Numbers
cyclic Pro-Hyp peak at 2 hours · 0.14–0.34 nmol/mL plasma levels · ~5% of linear Pro-Hyp levels · 7 nmol/mL enhanced fibroblast growth · LC-MS detection
How They Did This
Pilot study in human subjects who ingested collagen hydrolysate. Blood samples were collected at intervals and analyzed by liquid chromatography mass spectrometry (LC-MS) to detect and quantify cyclic Pro-Hyp levels. Cell culture experiments tested the effect of cyclic versus linear Pro-Hyp on mouse skin fibroblast growth on collagen gel.
Why This Research Matters
Collagen supplements are widely used for skin and joint health, but how they work after digestion has been unclear. This study identifies a previously unknown cyclic peptide form that appears in the bloodstream after taking collagen — and shows it stimulates skin cell growth more effectively than the well-known linear form. This could help explain why collagen supplements seem to benefit skin, even though the exact mechanisms have been debated.
The Bigger Picture
The collagen supplement industry generates billions in sales, but the science behind how oral collagen actually benefits skin has been incomplete. This discovery of a bioactive cyclic peptide form adds a new piece to the puzzle and may help explain why collagen hydrolysate shows clinical benefits despite the long-standing skepticism that oral collagen can survive digestion intact enough to matter.
What This Study Doesn't Tell Us
This is a pilot study with a small sample size. The cell culture work used mouse fibroblasts, not human cells. The plasma concentrations of cyclic Pro-Hyp were much lower than the concentration used in the cell culture experiments (7 nmol/mL), so it's unclear whether physiological levels would produce the same fibroblast-stimulating effect in living skin tissue.
Questions This Raises
- ?Do plasma concentrations of cyclic Pro-Hyp reach high enough levels in skin tissue to stimulate fibroblast growth in living humans?
- ?Does the ratio of cyclic to linear Pro-Hyp vary between different collagen supplement sources or formulations?
- ?Could cyclic Pro-Hyp be directly applied to skin for enhanced effects compared to standard collagen peptides?
Trust & Context
- Key Stat:
- ~5% of linear Pro-Hyp but more potent The newly discovered cyclic form was present at much lower concentrations but stimulated skin fibroblast growth more effectively than the standard linear peptide
- Evidence Grade:
- Rated low-moderate because this is a pilot study with a small human sample, and the fibroblast experiments were conducted in mouse cells at concentrations higher than those observed in human plasma.
- Study Age:
- Published in 2018, this was one of the first studies to identify cyclic Pro-Hyp in human blood after collagen ingestion. It remains relevant as foundational evidence for collagen peptide bioavailability research.
- Original Title:
- A Pilot Study for the Detection of Cyclic Prolyl-Hydroxyproline (Pro-Hyp) in Human Blood after Ingestion of Collagen Hydrolysate.
- Published In:
- Nutrients, 10(10) (2018)
- Authors:
- Shigemura, Yasutaka, Iwasaki, Yu, Tateno, Mana, Suzuki, Asahi, Kurokawa, Mihoko, Sato, Yoshio, Sato, Kenji
- Database ID:
- RPEP-03901
Evidence Hierarchy
A small preliminary study to test whether a larger study is feasible.
What do these levels mean? →Frequently Asked Questions
What's the difference between cyclic and linear Pro-Hyp?
Both are the same two amino acids (proline and hydroxyproline), but the cyclic form has a ring-shaped structure. This study found the ring shape was better at promoting skin cell growth in lab conditions, despite being present at lower levels in the blood.
Does this prove collagen supplements work for skin?
It adds evidence that bioactive peptides from collagen supplements do reach the bloodstream, including a newly discovered potent form. However, this pilot study doesn't prove clinical skin benefits — larger human trials measuring actual skin outcomes are needed for that.
Read More on RethinkPeptides
Cite This Study
https://rethinkpeptides.com/research/RPEP-03901APA
Shigemura, Yasutaka; Iwasaki, Yu; Tateno, Mana; Suzuki, Asahi; Kurokawa, Mihoko; Sato, Yoshio; Sato, Kenji. (2018). A Pilot Study for the Detection of Cyclic Prolyl-Hydroxyproline (Pro-Hyp) in Human Blood after Ingestion of Collagen Hydrolysate.. Nutrients, 10(10). https://doi.org/10.3390/nu10101356
MLA
Shigemura, Yasutaka, et al. "A Pilot Study for the Detection of Cyclic Prolyl-Hydroxyproline (Pro-Hyp) in Human Blood after Ingestion of Collagen Hydrolysate.." Nutrients, 2018. https://doi.org/10.3390/nu10101356
RethinkPeptides
RethinkPeptides Research Database. "A Pilot Study for the Detection of Cyclic Prolyl-Hydroxyprol..." RPEP-03901. Retrieved from https://rethinkpeptides.com/research/shigemura-2018-a-pilot-study-for
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.