Hydroxyprolyl-Glycine
Hydroxyprolyl-Glycine
Hydroxyprolyl-Glycine is a bioactive dipeptide that has emerged as a key component in collagen research and supplementation. This naturally occurring peptide, composed of 4-hydroxyproline and glycine amino acids, represents one of the most abundant and bioavailable fragments produced during collagen hydrolysis. As interest in collagen-based supplements continues to grow, understanding the specific role of Hydroxyprolyl-Glycine in supporting skin health, joint function, and overall connective tissue integrity becomes increasingly important. Research has demonstrated that this dipeptide can be absorbed intact through the intestinal wall and may directly contribute to collagen synthesis and tissue repair processes. For individuals seeking to support their body's natural collagen production through targeted supplementation, Hydroxyprolyl-Glycine offers a scientifically-backed approach to promoting healthy aging and maintaining tissue structure and function.
Medical Disclaimer
This content is for educational purposes only and does not constitute medical advice. Always consult a qualified healthcare provider before using any peptide.Read full disclaimer

Mechanism of Action
Hydroxyprolyl-Glycine (Hyp-Gly) is a bioactive dipeptide composed of 4-hydroxyproline and glycine, two amino acids that are fundamental components of collagen structure. This dipeptide functions through multiple interconnected pathways to support collagen metabolism and tissue integrity. Upon absorption, Hyp-Gly acts as a direct substrate for collagen synthesis, providing readily available building blocks that can be incorporated into newly formed collagen chains. The presence of 4-hydroxyproline is particularly significant, as this modified amino acid is essential for collagen stability through its role in forming hydrogen bonds that stabilize the collagen triple helix structure. Research indicates that Hyp-Gly may also function as a signaling molecule, potentially activating fibroblast proliferation and enhancing the expression of genes involved in collagen production, including COL1A1 and COL1A2. Additionally, this dipeptide may influence the activity of prolyl 4-hydroxylase, the enzyme responsible for hydroxylating proline residues in collagen synthesis. The bioavailability of Hyp-Gly is notably higher than that of intact collagen proteins, as dipeptides can be absorbed directly through peptide transporters in the intestinal wall without requiring complete hydrolysis to individual amino acids. This efficient absorption mechanism allows Hyp-Gly to reach target tissues more effectively, where it can contribute to collagen turnover, wound healing processes, and maintenance of extracellular matrix integrity in skin, joints, and other connective tissues.
Potential Benefits
Hydroxyprolyl-Glycine offers significant benefits for skin health and appearance through its direct involvement in collagen metabolism. Clinical studies have demonstrated that supplementation with collagen-derived peptides, including Hyp-Gly, can improve skin hydration, elasticity, and reduce the appearance of fine lines and wrinkles. The dipeptide's ability to stimulate fibroblast activity and collagen synthesis helps maintain skin structure and firmness, while its role in supporting the extracellular matrix contributes to overall skin integrity. Research has shown measurable improvements in skin moisture content and dermal density following consistent supplementation with collagen peptides containing Hyp-Gly. Beyond skin benefits, Hydroxyprolyl-Glycine supports joint health and mobility through its contribution to cartilage maintenance and repair. Cartilage tissue is predominantly composed of type II collagen, and the availability of collagen-building peptides like Hyp-Gly may help support cartilage structure and function. Some studies suggest that collagen peptide supplementation may help reduce joint discomfort and improve mobility in individuals with joint concerns. The dipeptide's role in wound healing and tissue repair processes also extends to supporting recovery from exercise-induced tissue stress and promoting overall connective tissue health throughout the body.
Common Use Cases
Dosage & Administration
Hydroxyprolyl-Glycine dosing is typically considered within the context of collagen peptide supplementation, as it is rarely available as an isolated compound. Most research has been conducted using collagen hydrolysate supplements containing 2.5-15 grams daily, which would provide varying amounts of Hyp-Gly depending on the source and processing method. For skin health benefits, studies have shown effectiveness with collagen peptide doses of 2.5-5 grams daily, typically taken once daily on an empty stomach or between meals to optimize absorption. Joint health applications have used higher doses, ranging from 8-12 grams daily, often divided into two doses taken with meals to improve tolerance. The timing of administration may be important, with some research suggesting that evening supplementation may align better with natural collagen synthesis rhythms. When starting supplementation, it's advisable to begin with lower doses (2.5 grams daily) and gradually increase to assess tolerance and response. Consistency is crucial, as collagen synthesis and tissue remodeling are ongoing processes that require sustained nutrient availability. Most studies showing significant benefits used supplementation periods of 4-12 weeks, suggesting that patience is required to observe meaningful results. Individual factors such as age, baseline collagen status, diet, and overall health may influence optimal dosing requirements. It's important to choose high-quality collagen hydrolysate products from reputable manufacturers to ensure adequate Hyp-Gly content and purity.
Safety Information
Long-Term Safety
Long-term use is generally considered safe with no significant adverse effects reported.
Research & Clinical Evidence
Research on Hydroxyprolyl-Glycine has primarily focused on its role within collagen hydrolysate studies, where it consistently appears as one of the most abundant and bioactive dipeptides. A landmark study by Iwai et al. (2005) demonstrated that Hyp-Gly and Pro-Hyp dipeptides could be detected in human blood plasma following oral collagen hydrolysate administration, establishing their bioavailability and absorption. Subsequent research by Ohara et al. (2007) showed that these collagen-derived dipeptides could stimulate hyaluronic acid synthesis in skin fibroblasts, suggesting a mechanism for skin health benefits. Clinical trials investigating collagen peptide supplementation, which contains significant amounts of Hyp-Gly, have shown promising results for skin health outcomes. A double-blind, placebo-controlled study by Proksch et al. (2014) involving 69 women aged 35-55 demonstrated significant improvements in skin elasticity after 4 weeks of collagen peptide supplementation. Additional research by Inoue et al. (2016) found that collagen peptides containing Hyp-Gly could improve skin hydration and reduce wrinkle formation. Joint health research has also shown positive outcomes, with studies by Clark et al. (2008) and Benito-Ruiz et al. (2009) demonstrating reduced joint discomfort and improved mobility following collagen peptide supplementation. While these studies don't isolate Hyp-Gly specifically, they provide strong evidence for the bioactivity of collagen-derived dipeptides in supporting tissue health and function.