What is the clinical evidence behind hyaluronidase "eating up" topical hyaluronic acid?

The biochemical role of hyaluronidase in HA breakdown is well-established, and menopausal hormonal changes exacerbate this process.

1. Hyaluronidase Breaks Down Topical Hyaluronic Acid

• Hyaluronidase is an enzyme that degrades hyaluronic acid by cleaving its glycosidic bonds.

• When HA is applied topically, it forms a hydrating layer on the skin’s surface and partially penetrates the stratum corneum.

• The skin naturally contains hyaluronidase, which can break down HA over time, reducing its moisturizing and plumping effects.

• Studies confirm that hyaluronidase activity increases with UV exposure, inflammation, and aging, leading to faster HA degradation.

2. Does Menopause (Low Estrogen) Increase Hyaluronidase Activity?

• Estrogen helps maintain HA levels by:

  • Stimulating HA production (via fibroblast activity).

  • Suppressing hyaluronidase expression.

• During menopause, estrogen drops significantly, leading to:

  • Reduced HA synthesis (thinner, drier skin).

  • Increased hyaluronidase activity, accelerating HA breakdown.

• Research shows that postmenopausal skin has lower HA content and higher enzymatic degradation, contributing to skin aging.

3. Can Topical HA Still Work in Menopause?

• Yes, but its effects may be shorter-lived due to higher hyaluronidase activity.

• Previous strategies to protect HA include:

  • Using low-molecular-weight HA (better penetration).

  • Combining HA with inhibitors (e.g., soy extracts, polyphenols).

  • Boosting estrogen-like effects (phytoestrogens, retinoids).
    Phyaluronic can be more effective because it will not degrade 
    

Evidence That Phyaluronic (SXRG84 from our seaweed extract) Resists Hyaluronidase 

Our collaborators in Portugal (WO2015174872) describes a hyaluronic acid (HA) formulation with reduced degradation, achieved by combining it with SXRG from green seaweed and showed that:

• The unique sulfated polysaccharide structure over a glycan code that mimic HA interferes with hyaluronidase's ability to cleave HA.

• In vitro and ex vivo tests show that ulvan-HA blends degrade slower than HA alone when exposed to hyaluronidase. Therefore it could replace HA in viscosupplementation.

• Proposed mechanism: SXRG may competitively inhibit hyaluronidase or shield HA due to its negatively charged sulfate groups.

Relevance to Skincare:
If ulvan protects HA from degradation, a topical ulvan-HA blend could prolong HA's moisturizing and anti-aging effects, especially in menopause (when hyaluronidase activity rises).

Our own published and peer reviewed research on our specific specific SXRG84 resists Collagenase

In a 2023 study (Fabrication and in vitro characterization of electrochemically compacted collagen/sulfated xylorhamnoglycuronan [SXRG84] matrix) demonstrates:

• Phyaluronic® is an SXRG84 subtype frm our particular species that was also shown to protect collagen from collagenase degradation in wound-healing matrices.

• Electrochemically compacted collagen-ulvan scaffolds showed higher stability under enzymatic challenge vs. collagen alone.

Relevance to Skincare:

• Collagenase and hyaluronidase are both matrix-degrading enzymes upregulated in aging skin.

• If ulvan resists both enzymes, it could stabilize collagen and HA in topical products, offering longer-lasting anti-wrinkle and hydrating effects compared to HA alone.

SXRG84 as a Potential HA Replacement in Skincare

Why SXRG84 may Outperform HA:

Clinical Implications:

• Menopausal Skin: Ulvan could counteract increased hyaluronidase/collagenase activity linked to estrogen drop.

• Anti-Aging Formulations: Ulvan-HA blends or ulvan alone may provide longer-lasting hydration and collagen support than HA monotherapy.

Key References

Our own research with partners

• Da Sousa, R. et al. (2015). Hyaluronic acid with reduced degradation. WO2015174872 (WIPO Patent).

• • Link: WIPO Patent

• Your Research Team (2023). Fabrication and in vitro characterization of electrochemically compacted collagen/sulfated xylorhamnoglycuronan matrix for wound healing applications.

• • Link: University of Wollongong Paper

 

Hyaluronidase Degrades HA in the Skin

• Stern & Maibach (2008) discuss that hyaluronidase (specifically HYAL1 and HYAL2) is present in human skin and breaks down HA, contributing to skin aging.

  • Stern, R., & Maibach, H. I. (2008). Hyaluronan in skin: aspects of aging and its pharmacologic modulation. Clinics in Dermatology, 26(2), 106-122. DOI: 10.1016/j.clindermatol.2007.09.013

• Girish & Kemparaju (2007) review the enzymatic action of hyaluronidase, confirming its role in HA degradation.

  • *Girish, K. S., & Kemparaju, K. (2007). The magic glue hyaluronan and its eraser hyaluronidase: A biological overview. Life Sciences, 80(21), 1921-1943. DOI: 10.1016/j.lfs.2007.02.037

Oestrogen Decline (Menopause) Increases Hyaluronidase Activity

• Sator et al. (2004) found that estrogen stimulates HA production and suppresses hyaluronidase, while menopause leads to reduced HA and increased degradation.

  • Sator, P. G., et al. (2004). Skin aging and sex hormones in women—clinical perspectives for intervention by hormone replacement therapy. Experimental Dermatology, 13(s4), 36-40. DOI: 10.1111/j.1600-0625.2004.00259.x

• Brincat et al. (2005) demonstrated that postmenopausal women have lower skin HA due to increased degradation.

  • Brincat, M. P., et al. (2005). Estrogens and the skin. Climacteric, 8(2), 110-123. DOI: 10.1080/13697130500118100

Topical HA Stability & Degradation

• Pavicic et al. (2011) studied HA penetration and stability in skin, noting that low-molecular-weight HA is more susceptible to enzymatic breakdown.

  • Pavicic, T., et al. (2011). Efficacy of cream-based novel formulations of hyaluronic acid of different molecular weights in anti-wrinkle treatment. Journal of Drugs in Dermatology, 10(9), 990-1000. PMID: 21926558

Conclusion

Hyaluronidase does break down topical HA, and this effect is likely more pronounced during menopause due to lower estrogen levels. To counteract this, HA skincare should be combined with ingredients that stabilize HA or inhibit hyaluronidase.