Significantly Enhanced Improvement in Dryness, Roughness, Fine Lines and Radiance Following Daily Use of a Novel Multi-Weight Hyaluronic Acid Plus Antioxidant Complex-Based Lotion Compared to a Single-Weight HA Plus Ceramide-Based Lotion

The glycosaminoglycan hyaluronic acid (HA) has multiple functions in humans, including maintenance of elastoviscosity of synovial joint fluid, control of tissue hydration and water transport, structural integrity of extracellular matrix, and numerous receptor-mediated roles in cell division and inflammation.^1–4 In skin, HA accounts for over 50 percent of the total body HA, where it serves as a humectant with its unique ability to bind up to 1,000 times its mass with water, providing skin with moisture and viscoelastic properties.^5–7

Skin aging is the result of a complex set of processes driven by both intrinsic metabolic driven reactions and extrinsic insults, including ultraviolet (UV) radiation and pollution.^{1, 8–11} The consequence of these processes results in the overall decrease in total HA concentration in skin, leading to a decrease in moisturization and structure visible as myofascial rigidity, dryness, fine lines and wrinkles.^12,13 

The use of topically applied HA has been shown to reduce some signs of skin aging;^5,14 however, these products contain only high molecular weight (HMW) HA, thus often result in only surface moisturization. Penetration of the epidermal surface by HA can only be accomplished by reducing the size of chain length of the HA to a lower molecular weight (LMW) molecule or by attaching to a permeable carrier.^1,15–17  

In this study, we describe the head-to-head clinical comparison of a novel multi-weight HA plus antioxidant complex-based lotion with SPF 30 and a single-weight HA plus ceramide-based lotion with SPF 30 for clinical efficacy on dryness, roughness, and fine facial lines following daily use.

Methods 

The two hyaluronic acid-based facial lotions evaluated in this study include a multi-weight HA plus antioxidant complex-based lotion with SPF 30 (Eucerin Face Immersive Hydration Daily Lotion SPF 30, Beiersdorf AG, Hamburg, Germany) and a single-weight HA plus ceramide-based lotion with SPF 30 (CeraVe AM Facial Moisturizing Lotion SPF 30, L’Oréal, Paris, France).

Study design. Written informed consent, as well as consent for photographic images, conforming to Title 21 of the Code of Federal Regulations 50.25 was obtained from each subject prior to enrollment in the study. The original signed informed consent form for each subject participating in the study was retained in the study file and each subject received a copy of the signed form. The study was reviewed and approved by an independent Institutional Review Board.

A double-blind comparative study was conducted on 70 female subjects (n=35, multi-weight HA plus antioxidant complex-based lotion with SPF 30; n=35, single-weight HA plus ceramide-based lotion with SPF 30) ages 25 to 65 years with mild to moderate facial dryness and visible fine lines and wrinkles, including subjects with Fitzpatrick Skin Types I to VI, with 20 percent having Fitzpatrick Skin Types V to VI. Clinical grading of the face, including dryness, roughness, and fine lines was assessed at baseline, 30 minutes, two weeks, four weeks, and eight weeks after once-daily application in the morning. Visible, cross-polarized (X-Pol), parallel-polarized (P-Pol) and UV fluorescence clinical images were acquired for each time point. X-Pol and P-Pol images were used to quantify skin radiance. Briefly, facial images were computer analyzed in terms of their image histogram parameters. A partial least squares regression model was then employed to quantify perceived radiance as a balance of skin surface and subsurface reflection components.

Results

Daily use of the multi-weight HA plus antioxidant complex-based lotion with SPF 30 demonstrated statistically significant improvements in all clinical grading assessments of dryness, roughness, and fine lines at Week 2 compared to baseline (p<0.05) and to the single-weight HA plus ceramide-based lotion group, while the daily use of the single-weight HA plus ceramide-based lotion with SPF 30 showed statistically significant improvement only in fine lines compared to baseline (p<0.05), with no improvement in dryness and roughness (Figure 1). 

By Week 4 of daily use, participants demonstrated statistically significant improvements in dryness, roughness, and fine lines compared to baseline for both products (p<0.05), with statistically significant enhanced improvement in dryness and roughness observed in the multi-weight HA plus antioxidant group compared to the single-weight HA plus ceramide group (p<0.05, Figure 2). 

At the final time point, Week 8, both lotions demonstrated statistically significant improvements in all three parameters: dryness, roughness and fine lines (p<0.05, Figure 3). When compared to each other, there was a statistically significant enhanced improvement in roughness and fine lines observed in the multi-weight HA plus antioxidant group compared to the single- weight HA plus ceramide group (p<0.05, Figure 3). 

Visible, cross-polarized, parallel polarized, and UV fluorescence clinical images were acquired for each time point and used to quantify skin radiance as previously reported by Matsubara et al.¹⁸ For radiance, daily use of the multi-weight HA plus antioxidant complex-based lotion with SPF 30 demonstrated significant increase in radiance at Week 4 compared with baseline, while the single-weight HA plus ceramide-based lotion did not show any improvement in skin radiance compared with baseline (data not shown).

Discussion 

An essential aspect to improving the appearance of chronologic/photoaging skin is increasing moisturization, leading to a decrease in roughness, fine lines, and superficial wrinkles. Use of topical formulations with HA can be beneficial in overall skin moisturization when properly formulated; unfortunately, the use of only high MW HA (as in most topical products) does not allow for leveraging the full benefits of HA due to the limited permeability of HMW HA. HMW HA hydrates the skin by creating a protective film on the surface that helps retain water, while LMW HA penetrates into the epidermal layer to moisturize the stratum corneum, creating a consistent epidermal texture.^7,19

We previously have reported on the development and clinical evaluation of a novel multi-weight HA plus antioxidant-based set of topical formulations with targeted delivery to enhance skin rejuvenation.²⁰ These unique formulations include both high and low MW HAs, allowing skin surface hydration/moisturization and epidermal penetration aimed at enhancing deeper skin hydration/moisturization and improving HA homeostasis.²⁰ The addition of the multifunctional antioxidants glycine saponin and glycyrrhetinic acid to these formulations further works to increase skin HA concentrations by inducing endogenous synthesis of HA and inhibiting the HA degrading enzyme HYAL1 along with the neutralization of reactive oxygen species and other free radicals.²¹ 

In this study, we describe the head-to-head clinical evaluation of two HA-based day lotions, one a novel multi-weight HA plus antioxidants-based lotion with SPF 30 and the other a single-weight HA plus ceramide-based lotion with SPF 30, applied daily for eight weeks with clinical grading of dryness, roughness, fine lines and radiance at baseline, Week 2, Week 4, and Week 8. As early as Week 2, the multi-weight HA plus antioxidant-based lotion demonstrated significant improvements in dryness, roughness, and fine lines versus baseline and enhanced improvement over the single-weight HA plus ceramide-based lotion in both dryness and roughness (Figure 1). This improvement in all three skin aging related parameters,were maintained through Week 8, the end of the trial, for the multi-weight HA plus antioxidant-based lotion (Figures 2 and 3). The single-weight HA plus antioxidant lotion also demonstrated significant improvements in all three parameters at Weeks 4 and 8, compared to baseline; however, the multi-weight HA plus antioxidant complex-based lotion continually demonstrated superior improvement in 2 to 3 of the parameters compared to the single-weight HA plus ceramide lotion (Figures 1–3). 

The clinical differences observed between the two HA lotions may be attributed to the ability of the multi-weight HAs to moisturize the skin surface and penetrate the upper surface layers of the skin combined with the added benefits of key antioxidants (glycine saponin and glycyrrhetinic acid) in stabilizing HA homeostasis.

Limitations. The limitations of this study include the relatively small sample size (n=35 per group), and the inclusion of only female subjects. Additional studies with larger populations, inclusion of both males and females, and an increase in the number of subjects with skin of color would be beneficial.

Conclusion 

HA is essential for maintaining skin moisturization. The reduction in the skin’s HA concentration can be driven by both exogenous and endogenous processes, leading to the appearance of signs of aging, such as dryness, roughness, fine lines and wrinkles. Use of topical HA formulations can be beneficial; however, it is essential for formulations to contain both high and low MW HAs for surface moisturization/hydration and deeper skin penetration to maximize the benefits of HA supplementation. The inclusion of antioxidants, including those which improve HA homeostasis, may further improve outcomes. This study demonstrates the clinical improvements in the appearance of skin aging after as early as two weeks of daily use of the multi-weight HA plus antioxidant complex-based lotion, with statistically significant enhancement in key skin parameters compared to a single-weight HA plus ceramide-based lotion, demonstrating the benefits of the multi-weight HA plus antioxidant approach aimed at enhancing skin rejuvenation. 

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