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Hyaluronic acid basics
First of all, hyaluronic acid isn’t as corrosive as it sounds – this molecule is naturally abundant in the dermis and epidermis of our skin. The hydration of the skin critically depends on the hyaluronic acid-bound water in the dermis and epidermis. The most superficial layer of the epidermis, the stratum corneum (SC), plays a crucial role in retaining this hydration.
The SC acts as a barrier to water loss. Signs of dehydration begin to appear when SC water content falls below 10%. If your skin is dehydrated you may notice the appearance of fine lines (or worsened fine lines), you may also have flaky skin, patchy foundation, amongst other indicators.
With ageing comes the disappearance of hyaluronic acid in the epidermis (the outermost layer of skin), whilst the acid is still present in the dermis (layer of skin that lies beneath the epidermis). With age the epidermis thus loses the main molecule responsible for binding and retaining water molecules, resulting in the loss of moisture from the skin and the characteristic signs of ageing skin. A reduction in the size of the hyaluronic acid polymers is also apparent in aged skin.
The whole premise behind hyaluronic acid in skincare is in its ability to attract water; hyaluronic acid is a humectant.
Humectants increase the water content of the skin by enhancing water absorption from the dermis into the epidermis. In extreme conditions it is also possible that humectants are able to draw in water from the external environment (when ambient humidity exceeds 70%). Humectants work since they contain hydrophilic groups which make them attracted to water molecules.
Hyaluronic acid is actually a polymer of disaccharides (essentially a polymer of sugar molecules – pictured above). Hyaluronic acid polymers can come in different sizes, hence why you might have come across the low vs high molecular weight debate in reference to the varying sizes these polymers are naturally present in/synthesised in.
Low vs high molecular weight hyaluronic acid
In general, ingredients with a smaller molecule size penetrate into deeper layers of the skin, while larger molecules work at the skin’s surface.
So it makes sense that high molecular weight hyaluronic acid acts as a humectant on the skin’s surface, while low molecular weight hyaluronic acid delivers hydration within the skin’s surface.
Although definitions vary, low molecular weight hyaluronic acid ranges from 20 to 300 kDa, while high molecular weight hyaluronic acid starts at 1,000 kDa (kDa being a unit of mass, the higher the number, the more it weighs).
Studies have found that hyaluronic acid with low molecular weight (20–300 kDa) passes through the stratum corneum. This is in contrast with the impermeability of high molecular weight HA.
Above roughly 300 kDa, hyaluronic acid stays on the surface of the skin, forming a barrier, locking in moisture. Whilst lower molecular weight hyaluronic acid penetrates the skin, helping to carry and hold water in the deeper layers, as well as triggering some key biological pathways.
Hyaluronic acid interaction with CD44 – why size matters
Hyaluronic acid participates in a number of cell surface receptor interactions; the CD44 receptor is one of hyaluronic acid’s primary receptors. This interaction triggers cellular responses and different metabolic processes in relation to the respective molecular weights. Approximately one third of cutaneous hyaluronic acid is contained in the epidermis where, by binding to the CD44 receptor, intervenes in the regulation of gene expression. Studies have shown that hyaluronic acid has a positive effect on the proliferation of skin fibroblasts (where CD44 plays a fundamental role). Studies have also shown hyaluronic acid can induce an increase in the production of collagen.
A 2022 study performed an in vitro evaluation on the influence of different molecular weights of hyaluronic acid on its binding to CD44. They demonstrated that low molecular weight hyaluronic acid and a complex of different molecular weight hyaluronic acids (high, medium, and low) increased the CD44 protein expression in human epidermal keratinocytes. Additionally, they showed that medium and high molecular weight hyaluronic acids couldn’t achieve this same effect. They concluded that the influence of the expression of CD44 by hyaluronic acid seemed to be dependent on the molecular weight.
Hyaluronic acid-containing skincare products could thus benefit from the inclusion of various weights of hyaluronic acid – the presence of low molecular weight hyaluronic acids would provide the benefit of CD44 stimulation, whilst higher molecular weight components would reside on the surface of the skin (due to an inability to penetrate the SC), providing the skin hydrating effects hyaluronic acid is well-known for.
What to look out for on ingredient lists
Hyaluronic acid vs sodium hyaluronate vs hydrolysed hyaluronic acid
Now if you’re into reading the ingredient lists of skincare products you may frequently see a product containing sodium hyaluronate, hyaluronic acid or hydrolysed hyaluronic acid. Or perhaps a combination of several. So what’s the difference?
A brief google search may lead you to the conclusion that hyaluronic acid has a high molecular weight, whereas sodium hyaluronate is the sodium salt version of hyaluronic acid, but with a lower molecular weight. What’s more confusing, sometimes a skincare product is marketed as containing hyaluronic acid but then you check out the ingredients list and come to find only the presence of sodium hyaluronate. So what’s the catch?
One thing’s for sure – and that’s that sodium hyaluronate is the sodium salt version of hyaluronic acid. Often companies use the term hyaluronic acid and sodium hyaluronate interchangeably. So you might wonder why is the sodium salt a thing and what’s this about it being of a lower molecular weight?
The sodium salt of hyaluronic acid is often used in formulations since it is actually more stable than hyaluronic acid, as well as being cheaper and easier to formulate.
Whilst sodium hyaluronate is sometimes of a lower molecular weight than hyaluronic acid, this is not always the case. It is not possible – just by looking at the ingredients list – to determine if the hyaluronic acid or sodium hyaluronate is high or low molecular weight.
What about hydrolyzed hyaluronic acid – this is a chemically broken down version of hyaluronic acid with a ‘low molecular weight’. Again, the ‘low molecular weight’ label here is kind of meaningless since we can get hyaluronic acid polymers that are low molecular weight.
How to tell the molecular weight
It’s essentially at the discretion of the brand to disclaim the molecular weight of the polymers they are using. This is not common practice, and at best you might find a declaration somewhere on the packaging that states the use of both high and low molecular weight hyaluronic acid (which can come in the form of hyaluronic acid, sodium hyaluronate or hydrolysed hyaluronic acid), but even then, you won’t get any exact weights.
If you cannot find a statement like this, it might be that the product only contains high molecular weight hyaluronic acid (in what ever form) since this has more immediate results (although, less long-lasting results).
Top hyaluronic acid picks
La Roche-Posay Hyalu B5 Pure Hyaluronic Acid Serum
This hydrating serum contains two different sized molecules of Hyaluronic Acid. The larger sized hyaluronic acid works at the surface of the skin to reduce wrinkles and re-plump the skin. Whilst the smaller molecule penetrates more deeply into the skin to increase skin volume. The serum also contains other actives; the presence of vitamin B5 helps with the natural skin repairing process and helps to repair damaged skin. Whilst madecassoside helps stimulate collagen synthesis.
Neutrogena Hydro Boost Hyaluronic Acid Serum
This budget-friendly best-seller contains both low and high molecular weight hyaluronic acid. The serum is hypoallergenic, non-comedogenic, and free of fragrance, parabens & mineral oil. The serum also contains vitamin B5 and water-magnet trehalose, helping to attract moisture and lock it in.
Paula’s Choice BOOST Hyaluronic Acid Booster
This booster contains both hyaluronic acid and sodium hyaluronate, supported by ceramides to reinforce the skin’s natural barrier.
Eucerin Anti-Ageing Hyaluron Filler Night Cream
This next generation hyaluronic acid cream features both high and low molecular hyaluronic Acid. It also contains the anti-oxidant saponin, which activates the skin’s own hyaluronic acid production by up to 256% and protects the skin from free radicals. Lastly, the presence of enoxolone decreases the degradation rate of hyaluronic acid by more than 50%.
THE ORDINARY Hyaluronic Acid 2% + B5
Of course we couldn’t forget The Ordinary’s hyaluronic acid, containing low, medium and high hyaluronic acid. The product also contains a next-generation hyaluronic acid crosspolymer. Cross-linking enhances the clinical longevity and mechanical characteristics of hyaluronic acid. The formulation is supported with the addition of Vitamin B5 which also enhances surface hydration.
Key takeaways
1) Look out for hyaluronic acid products with both high and low molecular weight forms (even medium too).
2) Hyaluronic acid may be listed as: hyaluronic acid, sodium hyaluronate or hydrolysed hyaluronic acid. Check for claims of their molecular weights, otherwise we’ve not much else to go off of.
References
Essendoubi, M., Gobinet, C., Reynaud, R., Angiboust, J. F., Manfait, M., & Piot, O. J. S. R. (2016). Human skin penetration of hyaluronic acid of different molecular weights as probed by Raman spectroscopy. Skin Research and Technology, 22(1), 55-62.
Snetkov, P., Zakharova, K., Morozkina, S., Olekhnovich, R., & Uspenskaya, M. (2020). Hyaluronic Acid: The Influence of Molecular Weight on Structural, Physical, Physico-Chemical, and Degradable Properties of Biopolymer. Polymers, 12(8), 1800.
Gruber, J. V., Holtz, R., & Riemer, J. (2022). Hyaluronic acid (HA) stimulates the in vitro expression of CD44 proteins but not HAS1 proteins in normal human epidermal keratinocytes (NHEKs) and is HA molecular weight dependent. Journal of Cosmetic Dermatology, 21(3), 1193-1198.
Mazzucco, A. (2019). Hyaluronic acid: evaluation of efficacy with different molecular weights. Int. J. Chem. Res, 1, 13-18.
