In the intricate world of metabolism, certain molecules often remain in the shadows despite their critical roles in maintaining our health. One such group of molecules includes 5-hydroxylysine and 4-hydroxyproline, lesser-known but crucial components in collagen maintenance. Let’s embark on a journey to uncover the significance of these molecules and their importance in the human body and their connection to the gut/skin axis.

What are 5-Hydroxylysine and 4-Hydroxyproline?

5-Hydroxylysine and 4-hydroxyproline are derivatives of the amino acids lysine and proline, respectively. They are distinguished by the presence of a hydroxyl group (-OH) attached to specific carbon atoms. These modifications transform lysine and proline into crucial building blocks for collagen, the most abundant protein in the human body and a crucial structural element in the skin, bones, tendons, and other connective tissues.

In Synthesis

Lysine and proline play pivotal roles in collagen stability and strength. Their incorporation into collagen fibers facilitates cross-linking, a process essential for the formation of strong connective tissues. As a result, these molecules contribute to the integrity of skin, bones, tendons, and other supportive structures throughout the body. As such, they play a fundamental role in maintaining skin firmness to promote elasticity and hydration. By supporting collagen synthesis, these molecules contribute to overall skin health and appearance.

In Degradation

While 5-hydroxylysine and 4-hydroxyproline play vital roles in collagen integrity, their high levels in the body reflect collagen degradation, which can also be influenced by various factors, including disease and environmental stressors. For extreme example, burn victims often exhibit elevated levels of these molecules due to the body’s response to tissue damage and the subsequent need for collagen regeneration. However, prolonged exposure to ultraviolet (UV) radiation can lead to the accumulation of excessive cross-linked collagen, including 5-hydroxylysine and 4-hydroxyproline, contributing to premature skin aging. While collagen degradation is a natural part of the healthy skin turnover process, inhibiting the breakdown of collagen and the release of these key metabolites can help counteract collagen loss. This can help delay the visible signs of aging like wrinkles, fine lines and sagging skin, and promote a more youthful complexion.


Collagen makes up much of the lamina propria, the basement layer of the intestinal epithelium and plays an important role in maintaining intestinal barrier function. Excessive collagen degradation can compromise the integrity of this structure and lead to leaky gut. The lamina propria is under stress and failure to maintain this matrix contributes to intestinal permeability, allowing inflammatory agents to pass through faulty tight junctions and leak into the blood stream. Inflammation can contribute to many health issues from diarrhea to constipation to skin issues such as acne, eczema, and rosacea.

In a recent study, Solnul® explored the role these molecules have in collagen metabolism and their gut-skin axis. 5-hydroxylysine, a marker of collagen degradation, was significantly reduced.1 Unpublished data shows that Solnul® consumption also significantly decreased levels of 4-hydroxyproline. These results emphasize the potential of supplementation with Solnul® to support collagen integrity, skin health and enhance gut barrier function.1

Global Trends

With rising concerns of global warming, increased UV rays can lead to higher levels of UV radiation exposure, exacerbating sun damage, premature aging, and skin cancer risk. Additionally, changes in temperature and pollution levels can contribute to dryness, inflammation, and allergic reactions, impacting overall skin health and comfort.

Lysine and proline are gaining popularity in the marketplace due to their recognized roles as important amino acids crucial for collagen synthesis, skin health, and overall wellness. These insights are valuable to formulators aiming to develop innovative gut health, beauty-from-within, and sports nutrition products aimed at supporting muscle recovery and joint health. Dietary supplement formulations that can focus on enhancing collagen synthesis while simultaneously minimizing collagen degradation, provide consumers with a holistic, all-in-one formulation.


Resistant potato starch supplementation reduces serum histamine levels in healthy adults with links to attenuated intestinal permeability


Gut/Skin Axis: Can Resistant Starch Influence Collagen Health?


1 Jason R. Bush, Jun Han, Edward C. Deehan, Scott V. Harding, Madhura Maiya, Joshua Baisley, David Schibli, David R. Goodlett, Resistant potato starch supplementation reduces serum histamine levels in healthy adults with links to attenuated intestinal permeability, Journal of Functional Foods, Volume 108, 2023, 105740, ISSN 1756-4646. Available here

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