What are the benefits of hyaluronic acid for the skin?

The hyaluronic acid is a glycosaminoglycan naturally present in the dermis and epidermis, where it helps maintain skin hydration. Its linear chemical structure, composed of repeating units of glucuronic acid and N-acetylglucosamine, endows it with an exceptional ability to attract and retain water. Indeed, a single molecule of hyaluronic acid can bind up to 1,000 times its weight in water, making it a benchmark humectant. This active ingredient is often likened to a molecular sponge. Interestingly, there are several forms of hyaluronic acid, which do not act in quite the same way to preserve the skin’s hydration.

Thus, high-molecular-weight hyaluronic acid (1 000–1 400 kDa) remains on the surface of the stratum corneum and forms a film that limits the evaporation of water molecules. Low-molecular-weight hyaluronic acid (20–300 kDa), by contrast, can penetrate the stratum corneum to lodge within the deeper layers of the epidermis and there retain the water molecules diffusing towards the surface. Certain forms of low-molecular-weight hyaluronic acid may also stimulate the expression of genes involved in the synthesis of filaggrin and epidermal lipids, which are essential for the proper functioning of the skin barrier.

By combining various types of hyaluronic acid in a formulation, comprehensive skin hydration is achieved at multiple scales. That’s why hyaluronic acid is an essential for dry skin.

The hydrating properties of hyaluronic acid, whether through topical application or injection, have been demonstrated in numerous studies. One notable example is the study conducted by Giannini and his team in 2022. Over four months, the 46 participants applied twice daily a serum of hyaluronic acid (concentration not specified). Hydration measurements were taken at each follow-up visit (weeks 2, 4 and 8), 15 minutes after cleansing, then 15 minutes after product application. The results demonstrated a progressive and statistically significant improvement in hydration of the skin, both in the short term and in the long term, with scores markedly higher than those observed at the beginning of the study.

Hyaluronic acid is, first and foremost, the ally of dehydrated skin.

Several intrinsic and extrinsic factors are responsible for the loss of skin firmness and the emergence of wrinkles. Among these is notably the gradual reduction in hyaluronic acid synthesis by dermal fibroblasts. Indeed, hyaluronic acid plays a crucial role in skin architecture. By filling the extracellular space, it supports collagen and elastin fibres and contributes to tissue cohesion. To counteract this reduction, it may be beneficial to use creams or serums rich in hyaluronic acid.

As mentioned above, the topical application of hyaluronic acid can act on multiple levels to reduce wrinkles and fine lines. First of all, its immediate humectant effect plumps up the skin’s surface, temporarily smoothing fine lines through a mechanical action. Moreover, low-molecular-weight forms penetrate deeper into the epidermis and modulate fibroblast activity. Several studies have demonstrated that hyaluronic acid can upregulate the expression of genes involved in type I and III collagen synthesis, as well as regulate matrix metalloproteinase MMP-1, one of the enzymes responsible for dermal matrix degradation.

This dual action – surface hydrating and deep restructuring – makes hyaluronic acid a benchmark active ingredient in treatments designed for mature skin.

Several clinical studies have demonstrated the benefit of hyaluronic acid in firming the face and reducing the signs of ageing. One of these was conducted on 34 women with moderate crow’s feet wrinkles. The objective was to compare the efficacy of a hyaluronic acid microneedle patch with that of a serum containing the same concentration of active ingredient. Each participant applied the patch to one side of the face and the serum to the other, twice weekly for eight weeks. Analysis of the results using instrumental measurements with a Cutometer revealed a significant improvement in wrinkles and skin elasticity in both groups from the first weeks. The results were markedly more pronounced with the microneedle patch.

This difference is explained by the improved penetration of hyaluronic acid through the skin barrier thanks to microneedles, allowing more direct access to the dermal fibroblasts. The visual assessment conducted by two independent dermatologists confirmed these observations, as did the participants’ own impressions, who reported a clearer reduction in wrinkles on the patch-treated side. Finally, no side effects or irritation were observed in either group, confirming the good tolerability of hyaluronic acid, even when delivered transdermally.

While hyaluronic acid is primarily recognised for its hydrating and plumping effects, its influence on the evenness of skin tone should not be underestimated. Indeed, this active ingredient contributes indirectly but significantly to reducing pigmentation irregularities and diffuse redness, giving the skin a more uniform appearance. This property of hyaluronic acid is explained by its barrier effect: by enhancing hydration of the stratum corneum, hyaluronic acid improves cell cohesion and limits external aggressions that can exacerbate pigmentary disorders, such as UV exposure, pollution or chronic inflammation. Moreover, several studies suggest that hyaluronic acid exerts an anti-inflammatory action, detailed further on, and modulates CD44 receptor expression, whose stimulation promotes cell migration, tissue repair and keratinocyte proliferation. In doing so, it favours more regular desquamation and a better distribution of melanin at the skin’s surface.

One of the studies mentioned above, in which 46 participants applied a hyaluronic acid serum twice daily, also examined the uniformity of their skin tone, focusing on both redness and pigmented spots. Photographs taken by the researchers throughout the study clearly demonstrate a reduction in erythema and hyperpigmentation, alongside an overall improvement in complexion evenness.

Another benefit of hyaluronic acid for the skin: it encourages wound healing following injury. It notably exhibits angiogenic properties, meaning that it can stimulate the formation of new blood vessels. Moreover, hyaluronic acid alters vascular permeability by activating endothelial cells involved in initiating the healing process. Finally, this active compound aids the binding between certain microbial membrane factors and Toll-like receptors, which promotes healing.

The wound-healing effects of hyaluronic acid vary according to its molecular weight.

An experimental study aimed to better understand this influence by evaluating various types of hyaluronic acid on human HaCaT keratinocytes and dermal fibroblasts, as well as in a murine skin wound model. In vitro, the researchers observed that keratinocyte proliferation and migration increased significantly with both the concentration and molecular weight of the active ingredient. In particular, high-molecular-weight hyaluronic acid (HA-K, 2290 kDa) stimulated the expression of several key cutaneous repair mediators, including interleukins IL-1β and IL-8, as well as vascular endothelial growth factor (VEGF). This form also promoted the expression of matrix metalloproteinases MMP-9 and MMP-13, which are involved in tissue remodelling.

In mice, topical application of HA-K to deep skin wounds yielded markedly superior results compared with the low-molecular-weight form (HA-B, 8 kDa) and the medium-molecular-weight form (HA-G, 987 kDa). From day one, a significant reduction in wound size was observed in the HA-K-treated group, accompanied by faster crust formation from day two – an indicator of the rapid initiation of the healing process. HA-B and HA-G creams nonetheless accelerated skin reconstruction in a manner similar to the reference formulation used as a control.

Hyaluronic acid does more than simply hydrate and regenerate the skin: it also has a soothing effect, particularly beneficial for sensitive skin prone to redness, tightness or itching. Hyaluronic acid acts in part by binding to the CD44 receptor on the surface of keratinocytes, thereby inhibiting the release of pro-inflammatory mediators such as interleukins IL-1β and IL-6 and prostaglandin E2, all of which are involved in irritation processes.

Hyaluronic acid also interacts with the RHAMM receptor, which plays a role in modulating inflammation. Located on the cell surface, RHAMM interacts with CD44 and modulates cell motility, wound healing, and signal transduction. Intracellularly, RHAMM binds to actin filaments and the mitotic spindle, thereby affecting crucial cellular processes involved in tumorigenesis, encompassing all stages leading to tumor formation. Owing to its anti-inflammatory properties, hyaluronic acid has been investigated in various studies to evaluate its efficacy in managing certain inflammatory dermatoses, such as eczema, psoriasis and rosacea.

Hyaluronic acid does not replace a dermatological treatment but can enhance its effects by providing a beneficial complementarity.

Finally, hyaluronic acid can be considered a protective agent against oxidative stress, a factor that contributes to premature ageing. This oxidative stress is caused by an accumulation of free radicals in the skin, generated, among other things, by UV rays, pollution or tobacco. Free radicals are unstable molecules that damage cellular components (lipids, DNA…), as well as the skin’s structural proteins, such as collagen and elastin. Low molecular weight hyaluronic acid is capable of trapping these free radicals before they can act.

A study in vitro compared the antioxidant activities of two low-molecular-weight forms of hyaluronic acid (LMWHA-1, 145 kDa, and LMWHA-2, 45 kDa) with those of high-molecular-weight hyaluronic acid (HMWHA, 1050 kDa) and vitamin C (VC). The results showed that LMWHA-1 exhibited the highest antioxidant activity, surpassing both LMWHA-2 and native HA, and in some cases even vitamin C. Radical scavenging assays revealed several types of activity:

• DPPH radical neutralisation: at 1600 µg/mL, LMWHA-1 achieved a scavenging rate of 59.38%, compared with 50.23% for LMWHA-2 and 53.65% for HA. Although these values are lower than those of vitamin C, they confirm significant antioxidant activity.

• Superoxide radical scavenging: LMWHA-1 demonstrated a neutralisation capacity of up to 87.12 % at 1250 µg/mL, compared with around 78 % for HA and LMWHA-2. This radical, a precursor of the hydroperoxyl anion (H₂O₂) and the hydroxyl radical, is particularly harmful to cellular membranes.

• Neutralisation of the hydroxyl radical, one of the most reactive: at 1120 µg/mL, LMWHA-1 achieved a scavenging capacity of 91.71%, surpassing HA (79.54%), LMWHA-2 (75.24%) and even vitamin C (80.40%).

The antioxidant effect of hyaluronic acid likely contributes to its overall role in preventing skin ageing.

• MAIBACH H. I. & al. Hyaluronan in skin: Aspects of aging and its pharmacologic modulation. Clinics in Dermatology (2008).

• MASSON F. Acide hyaluronique et hydratation cutanée. Annales de Dermatologie et de Vénéréologie (2010).

• GALL Y. Acide hyaluronique : structure, métabolisme et implication dans la cicatrisation. Annales de Dermatologie et de Vénéréologie (2010).

• ZENG X. & al. Antioxidant acitivity of low molecular weight hyaluronic acid. Food and Chemical Toxicology (2011).

• SCHLESINGER T. E. & al. Efficacy and tolerability of low molecular weight hyaluronic acid sodium salt 0.2% cream in rosacea. Journal of Drugs in Dermatology (2013).

• KIM D. & al. Hyaluronic acid microneedle patch for the improvement of crow's feet wrinkles. Dermatologic Therapy (2017).

• LEE J. H. & al. A hyaluronic acid‐based microneedle patch to treat psoriatic plaques: A pilot open trial. British Journal of Dermatology (2018).

• HANAWA T. & al. Wound healing promotion by hyaluronic acid: Effect of molecular weight on gene expression and in vivo wound closure. Pharmaceuticals (2021).

• LEE J. H. & al. Proteoglycan combined with hyaluronic acid and hydrolyzed collagen restores the skin barrier in mild atopic dermatitis and dry, eczema-prone skin: A pilot study. International Journal of Molecular Sciences (2021).

• REIS S. & al. Hyaluronic acid: A key ingredient in the therapy of inflammation. Biomolecules (2021).

• GIANNINI A. & al. Multicenter evaluation of a topical hyaluronic acid serum. Journal of Cosmetic Dermatology (2022).

• BRAVO B. & al. Benefits of topical hyaluronic acid for skin quality and signs of skin aging: From literature review to clinical evidence. Dermatologic Therapy (2022).