Oral supplementation with low-molecular-weight collagen peptides has been shown to improve skin hydration and elasticity while reducing wrinkles by influencing dermal fibroblast activity and extracellular matrix synthesis2,3. A systematic review and meta-analysis of randomized controlled trials confirmed that hydrolyzed collagen supplementation significantly enhances skin hydration and elasticity4. Further investigations indicate that collagen peptides rich in specific amino acid sequences, such as X-Hyp or X-Hyp-Gly, exhibit enhanced absorption and greater efficacy in promoting collagen synthesis within the dermis5. Beyond collagen, other dietary supplements, such as ceramides and hyaluronic acid, have also been recently investigated for their roles in enhancing skin health and moisture content6.
Collagen
Beyond direct synthesis, oral intake of enzymatically hydrolyzed collagen peptides has been shown to improve skin moisture and barrier function by increasing ceramide and natural moisturizing factor levels in the stratum corneum7. Concurrently, meta-analyses underscore the statistically significant impact of collagen supplementation on skin hydration and elasticity, often exceeding moderate effect sizes in key dermatological parameters8. For example, combined collagen and ceramide supplementation has been observed to yield a statistically significant increase in skin hydration and a concomitant decrease in transepidermal water loss compared to placebo9. This synergistic effect highlights the potential for multi-ingredient formulations to comprehensively address various aspects of skin aging, moving beyond single-agent interventions.

Collagen, a fibrillar protein composed predominantly of proline, hydroxyproline, and glycine, is the primary structural component of the dermal extracellular matrix, accounting for over 70% of the skin’s dry weight and providing essential density and elasticity10,11. As individuals age, a decline in type I collagen synthesis, exacerbated by intrinsic and extrinsic factors, contributes significantly to dermal thinning, loss of elasticity, and the formation of wrinkles12.
Collagen supplementation
Consequently, collagen supplementation aims to counteract age-related degradation by supplying precursors for collagen synthesis and stimulating endogenous collagen production13. For example, collagen hydrolysates from marine sources have been shown to reduce photoaging-induced wrinkle formation and improve moisture retention by increasing the expression of aquaporin 3 and CD44 in keratinocytes14.
Furthermore, these collagen peptides are absorbed into the bloodstream as di- and tripeptides, such as Pro-Hyp and Hyp-Gly, after oral ingestion. These peptides then target fibroblasts in the dermis to stimulate cell proliferation, hyaluronic acid synthesis, and extracellular matrix regulation15,16. This process enhances skin hydration by increasing hyaluronic acid production and improving overall structural integrity. The implantation of collagen has also been considered an effective strategy to improve extracellular matrix conditions and delay skin aging17.

Hyaluronic acid
This polysaccharide, integral to the extracellular matrix, is renowned for its exceptional water-retention capacity, thereby playing a pivotal role in maintaining skin turgor and viscoelasticity1. Endogenous hyaluronic acid production, however, diminishes with age, contributing to decreased skin hydration and elasticity, making supplementation an attractive strategy to replenish dermal hyaluronic acid levels18. Indeed, clinical studies have substantiated that oral intake of hyaluronic acid can significantly improve skin moisture, ameliorate dry skin conditions, and reduce the appearance of wrinkles, likely through its regenerative properties and its ability to enhance skin density and thickness19.
Hyaluronic acid supplementation
Oral hyaluronic acid supplementation has been shown to improve skin hydration and reduce wrinkles, with clinical trials demonstrating significant improvements in skin parameters such as stratum corneum water content and elasticity20. Beyond its direct hydrating effects, hyaluronic acid may also mitigate photodamage by reducing UV-induced inflammation and extracellular matrix degradation21,22. Nevertheless, the synergistic potential of co-administering these bioactive compounds warrants further investigation, particularly regarding their differential effects on distinct dermal cellular processes and matrix components. For instance, enhanced absorption of peptides such as Pro-Hyp and Gly-Pro-Hyp from collagen hydrolysates increases hyaluronic acid production in dermal fibroblasts, suggesting a functional interplay between these pathways11.

Ceramides
These lipid molecules are critical components of the stratum corneum, forming a protective barrier that regulates transepidermal water loss and maintains skin hydration. Their age-related decline or structural disorganization can impair barrier function, leading to increased skin dryness, sensitivity, and susceptibility to environmental stressors. Consequently, exogenous ceramide supplementation aims to restore barrier integrity and enhance the skin’s natural moisturizing capabilities, contributing to improved skin texture and resilience. Clinical trials have demonstrated that oral ceramide intake can notably augment skin hydration and barrier function, as evidenced by reduced transepidermal water loss and enhanced stratum corneum integrity.
Ceramides supplementation
Oral administration of sphingomyelin, a ceramide precursor, increases ceramide levels in the body, thereby improving skin hydration and barrier function, particularly in models of UV-induced photoaging23. This increase in epidermal lipid content and organization subsequently improves skin texture and resilience, underscoring the vital role of ceramides in maintaining dermatological homeostasis. The comprehensive benefits observed with ceramide supplementation underscore their potential as a therapeutic intervention for various dermatological conditions characterized by impaired barrier function.
Furthermore, ceramides, as vital constituents of the intercellular lipids in the stratum corneum, are crucial for establishing and sustaining the skin’s water-preserving capabilities6. A reduction in ceramide content within the stratum corneum has been directly linked to barrier disruption and xerosis, thereby necessitating topical or systemic interventions to restore optimal epidermal function24. For instance, low molecular weight hyaluronic acid modulates ceramide synthesis in human dermal fibroblasts, suggesting a complex interplay between different biomolecules in maintaining skin health25.
Conclusion
This interaction underscores the complexity of skin aging and the potential for synergistic effects from combined supplementation strategies. Oral supplementation with collagen, hyaluronic acid, and ceramides is a promising approach to enhancing dermal health and mitigating age-related skin deterioration. Future research should focus on optimizing dosages. and delivery methods for these compounds, while exploring the long-term efficacy and potential synergistic effects of their combined administration to further elucidate their precise mechanisms of action across diverse skin phototypes and conditions.
This continued exploration could also assess the efficacy of hydrolyzed fish cartilage in mitigating photoaging-induced skin changes, consistent with studies showing reduced wrinkles and increased dermal echogenicity28. Beyond these established agents, novel approaches are emerging, such as the “In & Out” strategy combining topical and oral melatonin, which has demonstrated improvements in lipid profiles and moisturization26. Additional areas of inquiry include the effects of probiotics, prebiotics, and postbiotics on aging skin, given their emerging roles in modulating the skin microbiome and barrier function27.
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