Hyaluronic acid is regarded as a “moisture magnet”: one gram can bind large amounts of water. But whether a serum only smooths the surface or acts more deeply depends above all on one factor – the size of the molecules. A review published in the journal Biomolecules in November 2025 has compiled the available evidence.
Not all hyaluronic acid is the same
Hyaluronic acid is a long-chain sugar molecule that occurs naturally in the skin, joints and eyes. For cosmetics, it is produced in different chain lengths. The review distinguishes:
- Low molecular weight: below 50 kilodaltons (kDa)
- Medium molecular weight: 100–500 kDa
- High molecular weight: above 700 kDa
How deeply does it penetrate?
The laboratory and skin studies cited show a clear relationship: the smaller the molecule, the deeper it gets.
- In a study on pig skin with twelve different forms, molecular size explained around 60 % of the differences in penetration. Of very small forms (0.4–100 kDa), more than half reached the dermis.
- Of forms with 200–500 kDa, about a quarter reached the dermis.
- A Raman spectroscopy study on human skin showed that 20–50 kDa reached a depth of up to 100 micrometres and 100–300 kDa up to 50 micrometres – very large molecules (1,000–1,400 kDa) remained in the outermost horny layer.
What do the different forms do?
High-molecular-weight hyaluronic acid forms a film on the skin surface. It reduces water loss and immediately makes the skin look smoother and plumper – a quick but superficial effect.
Low-molecular-weight forms (especially below 50 kDa) additionally showed effects on wrinkle depth and elasticity in clinical studies. They can reach deeper layers of the skin and interact with cells there.
Many products therefore combine several molecular sizes (“multi-molecular”) to combine surface and deeper effects.
Is it safe?
Based on clinical studies and independent assessments, the review rates hyaluronic acid in cosmetics as well tolerated. Research does, however, discuss the fact that very small fragments can also trigger pro-inflammatory signals in cell experiments – one reason why the size should not be arbitrarily small.
Practical tips
- Apply hyaluronic acid serums to slightly damp skin and “seal” them with a cream – in very dry air, water can otherwise evaporate from the skin.
- Look for information on molecular size; “hyaluronic acid” alone says little about the effect.
- Cosmetic hyaluronic acid does not replace daily sun protection – the most important protection against premature skin ageing.
Transparency note: the cited review was written by employees of a manufacturer of cosmetic ingredients (Givaudan). This article is for general information only and does not replace dermatological advice.
