What are the benefits of hyaluronic acid for the skin?

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 appearance of wrinkles. Among these factors is the progressive decrease in hyaluronic acid synthesis by dermal fibroblasts. Indeed, hyaluronic acid plays an important role in the skin’s architecture. By filling the extracellular space, it supports collagen and elastin fibers and contributes to tissue cohesion. To compensate for this decrease, 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, its immediate moisturizing effect plumps the skin’s surface, temporarily smoothing fine lines through mechanical action. In addition, low molecular weight forms penetrate deeper into the epidermis and modulate fibroblast activity. Several studies have shown that hyaluronic acid can stimulate the expression of genes involved in the synthesis of type I and III collagen, as well as the regulation of matrix metalloproteinase MMP-1, one of the enzymes responsible for dermal matrix degradation.

This dual effect – surface hydration plus deep restructuring – makes hyaluronic acid a benchmark active ingredient in skincare formulations for mature skin.

Several clinical studies have highlighted the benefit of hyaluronic acid for firming the face and reducing signs of aging. One such study involved 34 women with moderate crow’s feet wrinkles. The objective was to compare the efficacy of a hyaluronic acid microneedle patch with a serum containing the same concentration of active ingredient. Each participant applied the patch to one side of her face and the serum to the other, twice weekly for eight weeks. Instrumental analysis using a cutometer revealed a significant improvement in wrinkles and skin elasticity in both groups as early as the first weeks. The results were markedly more pronounced with the microneedle patch.

If hyaluronic acid is primarily known for its hydrating and plumping effects, its impact on skin tone uniformity should not be underestimated. Indeed, this active ingredient contributes in an indirect yet significant way to diminishing pigment irregularities and diffuse redness, giving the skin a more even appearance. This property of hyaluronic acid is explained by its barrier effect: by reinforcing hydration of the stratum corneum, hyaluronic acid improves cellular cohesion and limits external aggressors that can exacerbate pigment disorders, such as UV exposure, pollution, or chronic inflammation. Furthermore, several studies suggest that the hyaluronic acid exerts an anti-inflammatory action, discussed later, and modulates the expression of the CD44 receptor, whose stimulation promotes cell migration, tissue repair, and keratinocyte proliferation. In doing so, it encourages more regular desquamation and a better distribution of melanin on the skin’s surface.

One of the previously cited studies, in which 46 participants applied a hyaluronic acid serum twice daily, also examined the uniformity of their complexion—both in terms of redness and pigmented spots. Photographs taken by the researchers throughout the study clearly demonstrate a reduction in erythema and hyperpigmentation, as well as an overall improvement in skin tone uniformity.

Another benefit of hyaluronic acid for the skin: it promotes wound healing following injury. It notably has angiogenic properties, meaning it can stimulate the formation of new blood vessels. In addition, hyaluronic acid modifies vascular permeability by activating endothelial cells involved in the healing process. Finally, this active compound facilitates the binding of certain microbial membrane factors to Toll-like receptors, which promotes healing.

The wound-healing effects of hyaluronic acid vary depending on its molecular weight.

An experimental study sought 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 mediators of cutaneous repair, notably 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 remodeling.

In mice, topical application of HA-K to deep cutaneous wounds yielded markedly superior results compared to the low- (HA-B, 8 kDa) and medium- (HA-G, 987 kDa) molecular weight forms. From the first day, a significant reduction in wound size was observed in the HA-K-treated group, accompanied by faster crust formation from the second day - an indicator of the rapid onset of the healing process. The 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 just hydrate and regenerate the skin: it also provides a soothing effect, particularly helpful for sensitive skin prone to redness, tightness, or itching. Hyaluronic acid notably works 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 contribute to 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. Due to its anti-inflammatory properties, hyaluronic acid has been studied in various investigations to assess its effectiveness in managing certain inflammatory dermatoses, such as eczema, psoriasis and rosacea.

Finally, hyaluronic acid can be regarded as a protector against oxidative stress, a factor that contributes to premature aging. This process 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 able to trap these free radicals before they can act.

A study in vitro compared the antioxidant activities of two low-molecular-weight hyaluronic acid forms (LMWHA-1, 145 kDa and LMWHA-2, 45 kDa) to 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, outperforming both LMWHA-2 and native HA, and, in some cases, vitamin C. Radical scavenging assays revealed several types of activity:

• Neutralization of DPPH radicals: 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. While these values are lower than those of vitamin C, they still demonstrate significant antioxidant activity.

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

• Neutralization of the hydroxyl radical, one of the most reactive species: 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 aging.