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Which hyaluronic acid penetrates the deepest?

Which hyaluronic acid penetrates the deepest?

A few words on the history of hyaluronic acid.

Hyaluronic acid (HA), a member of the hyaluronan family, was first discovered by K. Meyer and John W. Palmer in 1934, and continues to draw the attention of chemists, biochemists, bioengineers, and other researchers from various scientific fields. Hyaluronic acid is a crucial component of extracellular and pericellular matrices, and can also be present within cells. The presence of hyaluronic acid in tissues varies: for instance, rooster combs contain 7.50 mg/ml, human umbilical cords (Wharton's jelly) about 4.10 mg/ml, human joint synovial fluid between 1.50 and 3.60 mg/ml, bovine vitreous humor between 0.14 and 0.34 mg/g, and human dermis and epidermis between 0.20 and 0.50 and 0.10 mg/g, respectively.

The unique characteristic of HA (Hyaluronic Acid) is its immense water-binding capacity. In solution, this polymer exists in a flexible and coiled configuration that allows it to retain approximately 1000 times its weight in water. This particular feature enables HA to contribute significantly to the maintenance of the extracellular space and to control tissue hydration.

These exceptional properties have thus predisposed HA to be a valuable component in skincare to combat dehydration and the early onset of aging signs. However, hyaluronic acid exists in various molecular weights, and can therefore penetrate the skin to varying depths.

Which hyaluronic acid penetrates the deepest into the skin when applied topically?

The process of skin hydration occurs through a very complex mechanism. Depending on the molecular weight of hyaluronic acid, it will act differently on skin hydration and the overall maintenance of the skin.

  • Thehigh molecular weight hyaluronic acid (> 1800 kDa) remains on the surface of the epidermis and forms an invisible film capable of blocking water evaporation, thereby preventing dehydration.

  • Theintermediate molecular weight hyaluronic acid (from 300 to 1800 kDa) provides the necessary water for the preservation of turgor and firmness.

  • Thelow molecular weight hyaluronic acid (below 300 kDa)penetrates the deepest ensuring an interaction with receptors and particularly with the CD44 protein (cluster of differentiation antigen glycoprotein) located on cell membranes. This interaction induces a reactivation of cellular metabolism to help combat environmental stress through mitosis and cell proliferation. A study also demonstrated that a 50 kDa hyaluronic acid penetrates the skin three times more than a 300 kDa hyaluronic acid.

Thus, the higher the molecular weight of hyaluronic acid, the more the molecule remains on the surface and its physicochemical properties are predominant. In the case of low molecular weight hyaluronic acid fragments, biological properties prevail and this type of active ingredient penetrates much deeper into the skin layers.

However, recent studies have shown that HA fragments of molecular weight less than 20 kDa are recognized by certain TLR (Toll-like receptors), leading to the production of pro-inflammatory mediators. It has also been demonstrated that 50 kDa hyaluronic acid does not cause any inflammatory effects on the skin when applied topically. As a precautionary principle, we recommend not applying hyaluronic acid to your skin if its molecular weight is less than 50 kDa.


  • Małgorzata Litwiniuk & al., Hyaluronic Acid in Inflammation and Tissue Regeneration, Wounds: a Compendium of Clinical Research and Practice (2016)

  • M. Farwick, P. Lersch, G. Strutz, Low Molecular Weight Hyaluronic Acid: Its Effects on Epidermal Gene Expression & Skin Ageing, SOFW-Journal, (2008)


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