Liposomal Hyaluronic Acid Enhances Skin Permeation and Hydration: Evidence from In Vitro, Ex Vivo, and In Vivo Studies

Nanoconstructs, such as liposomes, polymeric micelles, gold nanoparticles, carbon nanomaterials and nanocrystalline quantum dots, have been widely investigated for diagnostic, bioimaging and therapeutic applications [1]. Nanoconstructs have been also extensively explored in the field of dermatology. For example, liposomes and polymeric nanoparticles loaded with drugs were applied as topical administration agents for the treatment of skin diseases such as psoriasis, dermatitis and skin cancer [2,3]. Titanium dioxide and zinc oxide (ZnO) nanoparticles have been used as sun-screen formulation for the protection of skin from UV by the scattering, absorption and reflection of UV [4]. Silver nanoparticles are commercially used as wound and burn dressing agents with antibacterial effects [5]. Quantum dots and ZnO nanoparticles were utilized as bioimaging agents for the diagnosis of skin diseases [6,7]. Moreover, gold nanoconstructs and carbon nanomaterials have been actively investigated as promising agents for the photothermal ablation therapy of skin cancers due to their high light-to-heat conversion capability [8,9]. For further applications of nanoconstructs in dermatology, we need efficient transdermal delivery carriers of the nanoconstructs. The transdermal delivery has several advantages over other administration routes, such as oral delivery and needle based injection. The advantages include noninvasive treatment, self-administration, improved patient compliance and avoidance of hepatic first-pass metabolism or digestion system [10]. Despite these benefits, the low skin permeability of nanoconstructs such as polymers, proteins, hydrophilic drugs and nanoparticles limited their wide applications to the transdermal delivery. To facilitate the transdermal delivery of nanoconstructs, additional treatments have been adopted using penetration enhancers, iontophoresis, ultrasound and microneedles [11]. However, these methods require physical perturbations to the skin tissue, causing skin damage in some cases [12]. A noninvasive molecular carrier for transdermal delivery would have compelling advantages. The understanding for the characteristics of skin layers can be a good starting point for the development of transdermal delivery carriers of nanoconstructs. Stratum corneum (SC), the outermost skin layer, is the main barrier composed of densely packed dead cells forming hydrophobic surfaces. For the penetration of hydrophobic SC, hydrophobic molecules have clear benefits over hydrophilic molecules. The hydrophobic molecules can infiltrate into densely packed lipid layers in SC. However, nanoconstructs are usually formulated to have hydrophilic surfaces enhancing the physiological stability in the biological conditions. This contradicting requirement of hydrophobicity and hydrophilicity for transdermal delivery should be reconciled to enhance the physiological stability and the skin permeability by lipid disruption in SC. Recently, hyaluronic acid (HA) has been investigated as a promising transdermal delivery carrier. HA is a naturally occurring linear polysaccharide composed of repeating units of d-glucuronic acid and N-acetylEnhancing the transdermal penetration of nanoconstructs: could hyaluronic acid be the key?

Background and aimsExcessive exposure to the sun can cause severe photoaging as early as the second decade of life resulting in a loss of physiological elastic fiber functions. We designed a first study to assess differences in facial skin pH, sebum, elasticity, hydration and tonicity and serum levels of fibronectin, elastin, neutrophil elastase 2, hyaluronic acid and carbonylated proteins between patients affected by facial photoaging and healthy controls. In a second study we tested the hypothesis that a dietary supplement would improve facial photoaging, also promoting changes in the above mentioned skin and serum parameters. MethodsIn the first study we enrolled 30 women [age: 47.5±1.6years (mean±standard error of the mean)] affected by moderate facial photoaging (4cm≤Visual Analogue Scale (VAS)<7cm) and 30 healthy women [age: 45.9±1.6years (mean±standard error of the mean)]. In the second study we enrolled a cohort of 30 women [age: 43.6±1.2years (mean±standard error of the mean)], affected by moderate (n=22) and severe (VAS≥7cm; n=8) facial photoaging, who were randomized to receive a pharmaceutical formulation (VISCODERM® Pearls; IBSA FARMACEUTICI ITALIA Srl, Lodi, Italy) containing Pycnogenol®, collagen, coenzyme Q10, low-molecular-weight hyaluronic acid, chondroitin sulfate and glucosamine sulfate (n=15) or placebo (n=15). Dietary supplement and placebo were administered 2times a day for 4weeks. Facial photoaging was assessed by VAS in the first cohort of patients affected by facial photoaging and healthy controls and, at baseline and 2 weeks after the end of treatment, in the second cohort of patients who underwent treatment with VISCODERM® Pearls and placebo. Skin Tester was used to analyze differences in facial skin parameters between patients affected by facial photoaging and healthy controls. Skin Tester was also used to assess the effect of VISCODERM® Pearls on facial skin parameters and compared with placebo 2weeks after the end of treatment. Serum levels of fibronectin, elastin, neutrophil elastase 2, hyaluronic acid and carbonylated proteins were measured by enzyme-linked immunosorbent assay in the first cohort of patients affected by facial photoaging and healthy controls and, at baseline and 2weeks after the end of treatment, in the second cohort of patients who underwent treatment with VISCODERM® Pearls and placebo. ResultsVAS photoaging score was higher in patients affected by photoaging, if compared with healthy controls (p<0.0001). pH and sebum were increased in patients affected by photoaging, if compared with healthy controls (both p<0.0001), while elasticity, hydration and tonicity were decreased in patients affected by photoaging, if compared with healthy controls (all p<0.0001). Serum fibronectin and hyaluronic acid concentrations were lower in patients affected by photoaging, if compared with healthy controls (both p<0.0001). Serum neutrophil elastase 2, elastin and carbonylated protein concentrations were higher in patients affected by photoaging, if compared with healthy controls (p<0.01, p<0.01 and p<0.0001, respectively). Dietary supplement administration resulted in an improvement in VAS photoaging score, if compared with placebo (p<0.0001), as observed 2weeks after the end of treatment. Facial sebum, hydration and tonicity were increased in the active treatment group vs. placebo (p<0.0001, p<0.0001 and p<0.05, respectively) 2weeks after the end of treatment. Serum fibronectin and hyaluronic acid concentrations were increased in the dietary supplement group, if compared with placebo (p<0.01 and p<0.001) 2weeks after the end of treatment, while no statistical difference in serum elastin concentration was observed between the two groups. Serum neutrophil elastase 2 and carbonylated protein concentrations were decreased in the dietary supplement group 2weeks after the end of treatment, if compared with placebo (p<0.001 and p<0.0001). ConclusionsWe found significantly increased serum levels of neutrophil elastase 2, elastin and carbonylated proteins and decreased levels of hyaluronic acid and fibronectin in patients affected by facial photoaging, if compared with healthy controls. These findings coupled with a significant decrease in skin hydration, tonicity and elasticity and increased skin pH and sebum. Treatment with the dietary supplement VISCODERM® Pearls significantly improved VAS photoaging score and skin hydration, sebum and tonicity 2weeks after the end of a 4-week treatment period in patients affected by moderate to severe facial photoaging. These findings coupled with a significant increase in serum fibronectin and hyaluronic acid and a decrease in serum carbonylated proteins and neutrophil elastase 2 in the active treatment group, if compared with placebo. Our findings suggest that VISCODERM® Pearls is effective for treatment of facial photoaging but further studies in larger cohorts of patients are required.

Introduction: Hyaluronic acid (HA) has become a commonly used ingredient in many topical moisturizing products due to its strong humectant properties and essential role in skin hydration; however, limitations of delivery of HA to only the surface of skin has hindered leveraging the full capacity of HA biology necessary for skin rejuvenation. Here 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 plus ceramide-based lotion with SPF 30 for clinical efficacy on dryness, roughness, fine facial lines, and radiance following daily use. Methods: 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 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-VI, with 20% having Fitzpatrick Skin Types V-VI. Clinical grading of the face including dryness, roughness, and fine lines were assessed at baseline, 30 minutes, 2 weeks, 4 weeks, and 8 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. Results: Daily use of the multi-weight HA plus antioxidant complex-based lotion with SPF 30 demonstrated significant improvements in all clinical grading assessments of dryness, fine lines, and wrinkles as early as Week 2 compared to baseline. Improvements in visible dryness (Week 2), roughness (Week 2), and fine lines (Week 8) were greater for the multi-weight HA plus antioxidant complex-based lotion with SPF 30 compared to the single-weight HA plus ceramide-based lotion with SPF 30, with overall statistical significance across all three parameters assessed favoring the multi-weight HA plus antioxidant complex-based lotion with SPF 30. 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. Conclusions: The marked improvements in dryness, roughness, fine lines, and radiance following daily utilization of the multi-weight HA plus antioxidant complex-based lotion with SPF 30 may be attributed to the inherent properties of HA. These improvements may be further attributed to the ability of 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, including glycine saponin and glycyrrhetinic acid, which have been previously shown to induce endogenous HA synthesis and inhibit endogenous hyaluronidase activity in vitro, respectively.

Hyaluronan Metabolism in Human Keratinocytes and Atopic Dermatitis Skin Is Driven by a Balance of Hyaluronan Synthases 1 and 3

BackgroundThe molecular weight of hyaluronic acid (HyA) depends on the type of organ in the body. When HyA of the desired molecular weight is implanted into the human body for regeneration of damaged tissue, it is degraded by hyaluronidase in associated with an inflammatory response. This study sought to evaluate the effects of HyA molecular weight and concentration on pro- and anti-inflammatory responses in murine macrophages.MethodsThe structures and molecular weights of HyAs (LMW-10, MMW-100, MMW-500, and HMW-1,500) were confirmed by 1 H NMR and gel permeation chromatography (GPC), respectively. After treatment of murine macrophages with a low (10 µg/mL) or high (100 µg/mL) concentration of each molecular weight HyA, cells were stimulated with lipopolysaccharide (LPS) and changes in immune response in both LPS-stimulated and untreated macrophages were evaluated by assessing nitric oxide (NO) production, and analyzing expression of pro- and anti-inflammatory genes including by RT-PCR.ResultsMolecular weights of LMW-10, MMW-100, MMW-500, and HMW-1,500 were 13,241 ± 161, 96,531 ± 1,167, 512,657 ± 8,545, and 1,249,500 ± 37,477 Da, respectively. NO production by LPS-stimulated macrophages was decreased by increasing concentrations and molecular weights of HyA. At a high concentration of 100 µg/mL, HMW-1,500 reduced NO production in LPS-stimulated macrophages to about 45 %. Using NanoString technology, we also found that the immune-related genes TNF-α, IL-6, IL-1β, TGF-β1, IL-10, IL-11, CCL2, and Arg1 were specifically over-expressed in LPS-stimulated macrophages treated with various molecular weights of HyA. An RT-PCR analysis of gene expression showed that HMW-1,500 decreased expression of classically activated (M1) macrophage genes, such as TNF‐α, IL-6, CCL2, and IL-1β, in LPS-stimulated macrophages, whereas medium molecular-weight HyA (MMW-100 and MMW-500) instead increased expression levels of these genes. HMW-1,500 at a high concentration (100 µg/mL) significantly decreased expression of pro-inflammatory genes in LPS-stimulated macrophages. Expression of genes associated with anti-inflammatory responses (M2 phenotype), such as TGF-β1, IL-10, IL-11, and Arg1, were increased by high concentrations of MMW-500 and HMW-1,500 in LPS-stimulated macrophages.ConclusionsHigh molecular-weight HyA (i.e., > 1,250 kDa) inhibits pro-inflammatory responses in LPS-stimulated macrophages and induces anti-inflammatory responses in a concentration dependent manner.

Hyaluronic acid (HA) is a key component naturally present in the skin and is commonly used in skincare formulations and dermal fillers. Recently, there has been growing interest in oral HA supplementation for maintaining skin health and preventing aging due to its potential systemic benefits. This study aims to provide a comprehensive analysis of the efficacy of oral HA supplementation on various skin parameters, including hydration, elasticity, firmness, wrinkle reduction, and transepidermal water loss. Electronic databases (PubMed and Google Scholar) were searched for relevant articles. A total of 7 randomized controlled trials (RCTs) on the use of oral HA as a supplement were identified. A meta-analysis was performed to compare the standardized mean differences between the treatment (HA) and control (placebo) groups. The meta-analysis revealed statistically significant improvements in skin hydration, elasticity, and wrinkle depth following oral HA supplementation. Although the effects of oral HA on skin firmness, wrinkle volume, and transepidermal water loss were not statistically significant, a general trend of improvement was observed in these parameters. The findings of this analysis align with existing literature, underscoring the potential of oral HA supplementation as a valuable component in anti-aging and skincare regimens. However, the study's limited sample size and heterogeneity among included studies call for larger, more robust trials to confirm these findings and further explore the effects of oral HA on skin health.

The skin loses its moisture with advancing age, causing cosmetic issues such as wrinkles. In addition, the loss of moisture leads to hypersensitivity to external stimuli such as UV light. Transcutaneous supplementation with hyaluronic acid (HA) is an effective and safe method of recovering the moisturizing function and elasticity of the skin. However, the transcutaneous delivery of HA remains challenging owing to the barrier function of the stratum corneum (SC) layer. To penetrate the SC barrier, we used a reverse micelle formulation that does not require high energy consumption processes for preparation. We aimed to enhance the skin permeability of HA by incorporating glyceryl monooleate—a skin permeation enhancer—into the formulation. A fluorescently-labeled HA-loaded reverse micelle formulation showed significantly enhanced permeation across Yucatan micro pig skin. Fourier transform infra-red spectroscopy of the surface of the skin treated with the reverse micelle formulation showed blue shifts of the CH2 symmetric/asymmetric stretching peaks, indicating a reduction in the barrier function of the SC. Further study revealed that HA was released from the reverse micelles at the hydrophobic/hydrophilic interface between the SC and the living epidermis. The results demonstrated that our reverse micellar system is an easy-to-prepare formulation for the effective transcutaneous delivery of HA.

ABSTRACTBackgroundRosacea is a highly prevalent dermatosis affecting 5% of the world's population. Its impact is not only physical but also psychological, as over 60% of patients with rosacea also suffer from depression, anxiety, and other psychological comorbidities. Currently, topical treatments yield low or unsatisfactory success rates, and rosacea complications such as disfigurement, burning sensation, and pain can greatly affect patients' well‐being. Intra‐dermotherapy with high molecular weight non‐cross‐linked hyaluronic acid plus succinic acid has shown anti‐inflammatory, regenerative, and vascular modulatory effects.ObjectivesTo evaluate the efficacy and effectiveness of high molecular weight non‐cross‐linked hyaluronic acid (HMWNCHA) plus succinic acid (SA) mesotherapy in rosacea patients who are not responding to topical treatments. To determine the degree of improvement in general parameters such as erythema, telangiectasia, and skin laxity and hydration. To compare the cost of this treatment with that of laser therapy, a widely used modality.MethodsWe performed a non‐randomized, controlled interventional study, and we evaluated the results after three sessions (once monthly) as the primary endpoint of this mesotherapy, using a product containing 1.1% of high molecular weight non‐cross‐linked hyaluronic acid plus 1.6% succinic acid (full face, 2 mL per session, administered using the papule technique) in a group of 20 male and female patients, aged 40–45 years, Fitzpatrick skin types I–III, without comorbidities. All patients were already undergoing topical treatment with Ivermectin 1%, Metronidazole 0.75%, and photoprotection, but without good results or clear improvement, quantified as a reduction in the Investigator's Global Assessment (IGA) severity score of at least 1 point. Erythema, hydration, and facial telangiectasia were evaluated at every session for proper quantification. Our study group was compared with a control group that only continued their topical treatment, and the study lasted 4 months, with a prospective follow‐up at 6 months.ResultsOur results showed a reduction of 80% in the baseline erythema, an improvement of 30% in skin hydration, and a reduction of 20% in facial telangiectasia after three sessions, compared with patients who used only topical treatment. In addition, the costs were significantly lower than those of three sessions of laser therapy in a private healthcare setting.ConclusionWe demonstrated that using this acid combination in mesotherapy is an efficient, safe, and cost‐effective adjunct therapy for patients already using a particular topical treatment.

The elasticity of the skin and its capacity to hold water decrease with aging because of the loss of hyaluronic acid (HA) in the skin. Therefore, there is an increasing interest in the use of HA fillers in skin rejuvenation beyond its conventional use which is supplementing decreased dermis volume and filling deep wrinkles. We investigated the efficacy and safety of a novel device (Dermashine balance) that injects HA into the dermis using a stamp-type microneedle for maintenance of hydration and elasticity of the skin. A single-center randomized double-blinded parallel-group clinical study was conducted, and 60 participants enrolled in this study. The subjects were randomized to receive HA injections or a placebo three times across the face using an automatic intradermal injector. At 4, 8, and 12 weeks after the treatment, skin hydration was measured using a corneometer. The patients who received HA showed significantly greater skin hydration than those who received the placebo. However, a significant difference was not noted in skin elasticity between the groups. No severe adverse event was reported. Intradermal supplementation of HA using mesogun multineedle injector may be a safe and effective treatment for improving skin hydration.

Introduction: Hyaluronic acid (HA) has become a commonly used ingredient in many topical moisturizing products due to its strong humectant properties and essential role in skin hydration; however, limitations of delivery of HA to only the surface of skin has hindered leveraging the full capacity of HA biology necessary for skin rejuvenation. Here we describe the clinical efficacy data of a set of novel next-generation, multi-weight HA plus antioxidant complex-based topical formulations with targeted skin delivery to enhance skin rejuvenation, giving a youthful, healthy appearance. Methods: Four multi-weight HA plus antioxidant complex-based formulations: 1) Multi-Weight HA plus Antioxidant Complex Cream with SPF 30 (Day Cream); 2) Multi-Weight HA plus Antioxidant Complex Cream (Night Cream); 3) Multi-Weight HA plus Antioxidant Complex Gel Cream; and 4) Multi-Weight HA plus Antioxidant Complex Boost Serum were clinically evaluated for key attributes including moisturization via corneometer, with clinical grading of: dryness, roughness, fine lines and wrinkles, and following daily use of the individual products for up to 8 weeks. Results: Daily use of the multi-weight HA plus antioxidant complex-based formulations demonstrated significant improvements in all parameters evaluated compared to baselines, with changes in moisturization observed within 30 minutes of application, and changes in clinical grading parameters of dryness, roughness, fine lines and wrinkles observed as early as 2 weeks. Conclusions: These data demonstrate the clinical benefits of daily use of multi-weight HA plus antioxidant complex-based moisturizers for overall improvement in skin health and appearance.

There is an interesting relationship between the skin and fermentation of lactic acid bacteria (LAB) or bifidobacteria. Supernatants of these bacteria contain lactate and amino acids, which contribute to the hydration of the skin. Many cosmetic ingredients have been developed using LAB and bifidobacteria. In this chapter, four cosmetic ingredients that are being developed are introduced. Skim milk fermented by Streptococcus thermophilus (SE) has skin hydration, antioxidative, and pH control effects. Moreover, the cell protective effect of this ingredient has been proven in recent research. Aloe vera fermented by Lactobacillus plantarum, which was selected from 119 strains of LAB (AE), possesses fourfold greater skin hydration effect than nonfermented A. vera juice. Soybean milk fermented by Bifidobacterium breve has the potential to enhance hyaluronic acid production in three-dimensional culture of human cells. S. thermophilus YIT 2084 was proven able to produce hyaluronic acid. Although hyaluronic acid is a conventional cosmetic ingredient, it has the added value of being safe owing to its production using S. thermophilus, which is generally recognized as safe. It is believed that the technology introduced here will be useful for the development of next-generation cosmetic ingredients .

Hydrophobically-modified hyaluronic acid as stabilizer for oil-in-water emulsions to improve epidermis biodistribution of actives.

Hyaluronic acid (HA), a high molecular weight glycosaminoglycan of the extracellular matrix involved in growth, inflammation and wound healing, also contributes to the hydration and plastic properties of skin. Several drug and cosmetic formulations contain HA. We have initiated investigations that explore whether it is possible, by topical application, to modulate endogenous HA levels in skin. We developed a model epidermal culture system that exhibited a differentiated stratum corneum, and expressed HA and the HA receptor CD44, in a pattern similar to that observed in intact skin. Such in vitro skin equivalents are useful models for investigating the effect of topical drugs. HA and bacterial hyaluronidase were applied to the in vitro skin equivalent and to human skin. Their effects on endogenous HA and CD44 expression were examined using histochemical analysis. Topical HA treatment had no significant effect on HA or CD44 expression in either system. However, hyaluronidase decreased HA and CD44 expression in a dose-dependent manner in both the epidermal culture system and in skin. Apparently, HA is not able to permeate the epidermal culture system or human skin to a significant degree, but bacterial hyaluronidase does permeate both human skin and the culture system, depleting HA and decreasing CD44 expression. These effects were more prominent in the dermal than in the epidermal layers, suggesting that marked differences in HA metabolism exist in these two skin compartments. The ability of hyaluronidase to permeate the stratum corneum suggests that topical application may, additionally, be useful as a clinical modality.

IntroductionAlthough various products are commonly used for skin rejuvenation, solid-type hyaluronic acid (HA) as an injectable form has not been researched or utilized. This study aimed to demonstrate the safety and efficacy of solid-type HA in thread form, which differs from the conventional gel-type HA commonly used.MethodSolid-type HA threads, conventional HA fillers, and polydioxanone (PDO) threads were inserted into the dorsal subcutaneous layer of mice. Photographs were taken on days 0, 1, 3, and 7, and on day 7, the samples were harvested for histological analysis. Inflammatory reactions and detection of collagen were confirmed through tissue staining, and real-time PCR was conducted to quantify collagen synthesis.ResultsIn the histological analysis, the PDO threads exhibited a greater inflammatory response compared to the HA threads. Masson’s trichrome staining revealed a higher degree of collagen synthesis in the HA thread group compared to the HA filler group. While collagen type 1 expression was significantly higher in the PDO thread group than in the HA thread group, the HA thread group showed higher expression levels of collagen type 3. Furthermore, the PDO thread group demonstrated a statistically significant increase in TGF-β1 compared to the HA group.ConclusionThis in vivo study demonstrated the stable application of solid-type pure HA threads and their potential for inducing collagen production, while also yielding a low inflammatory response. The findings highlight the promising applications of solid-type HA in the field of cosmetic dermatology.No Level AssignedThis journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

ABSTRACTCollagens and hyaluronic acid have long been used in pharmaceuticals and food supplements for the improvement of skin elasticity and hydration. These compounds provide the building blocks of the skin. Ovoderm is an oral supplement obtained from eggshells that contains naturally occurring collagen and glycosaminoglycans, such as hyaluronic acid. We evaluated the efficacy of Ovoderm on skin biophysical parameters related to cutaneous aging such as elasticity, hydration, and pigmentation. Two pilot studies were run to assess the effect of daily oral supplementation with 300 mg Ovoderm on skin parameters. The first consisted of a self-assessment questionnaire intended to perform an assessment on skin, hair, and nail health after 50 days of treatment. The second measured the effect of 5-week treatment on hydration by corneometry, on elasticity with the cutometer, and on pigmentation with the mexameter. In the pilot study 1, participants were predominantly satisfied with the effects obtained on general face (100% volunteers satisfied) and body (94% volunteers satisfied) skin condition and skin properties (100% volunteers satisfied with facial skin softness, 94% with facial skin hydration, and 89% with body skin hydration) and partly with effects on hair (67% volunteers satisfied) and nail (50% volunteers satisfied) condition. The study 2 revealed a statistically significant improvement in skin elasticity (12% increase, p =.0136), a tendency to reduce skin pigmentation (5% decrease), and no significant change in skin hydration. Our study reflects that oral supplementation with Ovoderm is efficacious to reduce the gradual loss of skin elasticity characteristic of aged skin, which helps to improve the appearance of the skin.