How Does Moisturizing Function of Hyaluronic Acid Differ Depending on Molecular Size?

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How Does Moisturizing Function of Hyaluronic Acid Differ Depending on Molecular Size?

Hyaluronic acid (HA), one of the most highlighted ingredients in skin hydration, exhibits significantly different efficacy and mechanisms of action depending on its molecular size. Naturally produced in the human body, HA plays a vital role in maintaining skin moisture. However, as we age, the amount of HA in the body decreases, which becomes one of the major causes of skin aging.

Hyaluronic acid possesses remarkable water-retention capacity, being able to attract up to 6 liters of water per gram. Due to this property, many cosmetic brands use HA as a key ingredient. However, not all hyaluronic acid has the same effect. Its impact on the skin and how it functions vary greatly depending on its molecular weight—that is, its molecular size.

Hyaluronic acid’s molecular weight is measured in Daltons (Da or kDa). Generally, it is categorized into high-molecular-weight HA (HMW-HA), mid-molecular-weight HA (MMW-HA), low-molecular-weight HA (LMW-HA), and ultra-low-molecular-weight HA (ULMW-HA). Each of these molecular sizes plays a different role in the skin, and selecting the appropriate type according to one’s skin condition and desired effect is crucial.

High-molecular-weight HA, with a molecular weight of 1,000,000 Da (1,000 kDa) or more, refers to large molecules. These molecules remain on the skin’s surface, forming a protective barrier that prevents water loss. Because they are too large to penetrate the skin, they stay on the epidermis and create a film that shields the skin from external irritants while locking in moisture. This makes HMW-HA particularly effective in dry environments for maintaining surface hydration.

Additionally, due to their large size, HMW-HA molecules remain on the skin longer, providing sustained hydration. They draw water to the skin’s surface, delivering an immediate moisturizing effect, which is helpful for rapid relief from dryness.

Mid-molecular-weight HA generally ranges from 100,000 to 1,000,000 Da (100–1,000 kDa). Though smaller than HMW-HA, it still struggles to penetrate deeply into the dermis. MMW-HA acts between the epidermis and dermis, offering hydration to both layers. It forms a protective layer on the skin surface and partially penetrates the upper epidermis, providing more profound moisturization than HMW-HA.

Low-molecular-weight HA, with a molecular weight between 10,000 and 100,000 Da (10–100 kDa), can penetrate through the epidermis due to its small size. LMW-HA delivers moisture deep within the skin and promotes skin cell regeneration. It is quickly absorbed and offers immediate hydration, helping to repair damaged skin efficiently.

Ultra-low-molecular-weight HA, with a molecular weight of 5,000 Da (5 kDa) or less, has the smallest particle size. This enables it to penetrate deeply into the skin, reaching the dermis. ULMW-HA stimulates skin cell activity and promotes collagen production, thereby improving skin elasticity and reducing the appearance of wrinkles. It delivers long-term hydration from the deeper layers of the skin.

The functional differences in HA based on molecular weight are not solely due to penetration depth. Biological effects also vary by size. For instance, HA at 50 kDa shows anti-inflammatory properties, while HA at 1,500 kDa is known to assist in collagen synthesis. These findings underscore the multifaceted influence of HA on skin depending on molecular size.

However, smaller molecular sizes—while enhancing absorption—also tend to degrade more quickly. The half-life of HA is approximately 3–5 minutes in the bloodstream, about one day in the skin, and 1–3 weeks in cartilage. The smaller the molecule, the shorter its half-life tends to be, which may limit its long-lasting efficacy in the skin.

For this reason, multi-molecular HA formulations, which combine various molecular weights, are increasingly popular. For example, triple hyaluronic acid formulations integrate HMW-, MMW-, and LMW-HA to provide multi-layered hydration from the skin’s surface to deeper layers. Some brands have introduced products with five or even seven different molecular weights to maximize these benefits.

A well-known Japanese brand, Hada Labo, is famous for products that utilize three different HA types: standard HA, super HA (with double the water retention capacity), and micro HA (1/200 the size of standard HA). These formulations hydrate the skin in stages and form a moisture barrier, prolonging the moisturizing effect.

When selecting HA products, it’s essential to consider your skin condition and your skincare goals. If immediate hydration and moisture barrier protection are needed, a product containing HMW-HA would be suitable. If deeper hydration and improved elasticity are desired, products containing LMW- or ULMW-HA would be more effective. Ideally, choosing a product with multiple HA sizes provides comprehensive moisturization from the skin surface down to the dermal layers.

HA is generally safe for all skin types. It is non-irritating and rarely causes allergic reactions, making it suitable even for sensitive skin. It also works synergistically with other skincare ingredients.

For best results, HA products should be applied to slightly damp skin. Applying HA serum or cream on skin that has been moistened with a toner or mist enhances its ability to draw moisture into the skin.

Though naturally produced in the body, hyaluronic acid levels decrease with age. After our 20s, HA production declines, dropping to half by our 30s and to about a quarter by our 50s compared to levels in our 20s. This reduction leads to dryness, loss of elasticity, and wrinkles—key signs of skin aging. Therefore, external supplementation of HA becomes increasingly important with age.

HA is not only a hydrating agent but also supports skin regeneration and has anti-inflammatory properties, making it helpful in treating acne and wound healing. Especially, LMW-HA demonstrates anti-inflammatory effects, making it effective in calming irritated and sensitive skin.

In recent years, advanced technologies have been developed to stabilize HA and improve its skin absorption. Methods such as encapsulation, specialized delivery systems, and stabilization techniques to slow degradation have been studied to enhance HA’s efficacy.

Beyond cosmetics, HA is widely used in the medical field. Hyaluronic acid fillers are utilized to smooth wrinkles and add volume, while injectable HA is also used for osteoarthritis treatment. This broad utility highlights the proven efficacy of HA across domains.

Here is a summary of hyaluronic acid functions by molecular size:

• High-Molecular-Weight HA (1,000 kDa or more)
– Forms a protective barrier on the skin’s surface
– Prevents moisture loss
– Provides immediate hydration
– Shields the skin from environmental factors

• Mid-Molecular-Weight HA (100–1,000 kDa)
– Acts between epidermis and dermis
– Offers surface protection and partial penetration
– Delivers balanced hydration

• Low-Molecular-Weight HA (10–100 kDa)
– Penetrates the epidermis
– Promotes skin cell regeneration
– Absorbs quickly for immediate hydration
– Supports recovery of damaged skin

• Ultra-Low-Molecular-Weight HA (≤5 kDa)
– Penetrates into the dermis
– Stimulates collagen production
– Enhances skin elasticity
– Reduces wrinkles
– Provides long-term hydration from deeper layers

As each molecular size of HA offers different benefits, choosing the right type based on your skin’s needs is essential. Products with HMW-HA are suitable for immediate surface hydration, while those with LMW- or ULMW-HA are better for targeting elasticity and wrinkle reduction. The most comprehensive approach is using products that combine multiple molecular sizes of HA to achieve layered hydration and skin health.

Hyaluronic acid is generally safe across all skin types but should be selected considering individual skin conditions and potential interactions with other skincare products. Applying it to slightly moist skin and sealing in moisture with a cream or oil afterward will enhance its effectiveness and prevent moisture evaporation.

In conclusion, hyaluronic acid offers various moisturizing functions and benefits depending on its molecular size. Understanding these differences allows for more effective skin management. Multi-molecular HA products provide hydration from the surface to deeper layers of the skin, supporting healthy, hydrated, and youthful skin.