Selling skincare science
Does anyone really know how hyaluronic acid works?
If you grew up reading fashion and beauty magazines in the 1990s like I did, you’ll be familiar with print advertisements that looked a little something like this:
Yes, alright, this particular advertisement is from 1909, but the marketing strategies of the 1990s and early 2000s were often just as retro. Companies dabbled in pseudoscience to peddle their wares, but the copy was as light on scientific terminology as it was lacking in scientific reality (my personal favourites were products with extracts of immortal flowers that would allegedly impart immortality to your dermis).
The marketing that accompanies skincare products released today couldn’t be more different. Take the inexpensive and supremely popular serum from The Ordinary, Hyaluronic Acid 2% + B5. Instead of making claims about the transformative powers of the product, The Ordinary launches into a description of the formula which wouldn’t look out of place in a journal of dermatology:
Hyaluronic Acid (HA) can attract up to 1,000 times its weight in water. The molecular size of HA determines its depth of delivery in the skin. This formulation combines low-, medium- and high-molecular weight HA, as well as a next-generation HA crosspolymer at a combined concentration of 2% for multi-depth hydration.
This unconventional skincare brand, owned by parent company DECIEM, launched their clinically-branded products in 2016, amidst a sea of midnight recovery complexes, youth drops, sublime skin creams and various essences of immortality.
The skincare landscape has changed dramatically in the last decade, for a multitude of reasons. Strikingly, everyone’s suddenly a skincare nerd. I used to pride myself on being able to decipher ingredients list, but it seems that’s no longer a unique skill. The beauty blogs that I follow now not only include soundbites from dermatologists in their product reviews, but provide links to scientific literature.
As a skincare enthusiast with a background in materials engineering and chemistry, I wanted to delve into how skincare companies convey the science of skincare and what this means for the consumer. Are companies accurately describing their products? Do they do a good job of explaining how they work? And do consumers glean anything useful when selling science is part of a marketing model? I explored one of the main players of the scientific skincare arsenal, hyaluronic acid, to find out.
What is hyaluronic acid?
Perusing popular beauty websites and direct-to-consumer retailers, you’ll read that HA is a naturally occurring substance found in our skin. You may see it described as a polysaccharide (that means it’s composed of a long chain of carbohydrate molecules), or a molecule called a glycosaminoglycan (a polysaccharide with double sugar units).
A word that doesn’t often pop up describing HA skincare is ‘polymer’ (except on The Ordinary’s site, but they’re the exception). Perhaps that’s understandable. Most of us associate polymers with plastic, and plastic is a decidedly unsexy skincare ingredient. A polymer is simply a large molecule composed of many repeated subunits: smaller molecules known as monomers. Natural polymers (which include DNA and proteins) and synthetic polymer like plastics are ubiquitous and indispensable to life.
HA is composed of repeating units of much smaller saccharide (sugar) molecules, and one HA molecule might contain 20,000 saccharide monomers. In the image below, you can see the skeletal formula of the monomer, which shows how the sugar molecules are bonded. HA is a glycosaminoglycan, a type of polysaccharide with a long, linear molecular structure (meaning the monomer is repeated in a linear chain, and the polymer doesn’t have branching links between the chains).
Molecular size is a hot topic for the (very large) HA molecule. When it comes to molecules, size is generally measured in terms of weight, which tends to be measured in daltons. A molecule of HA that occurs naturally in the skin averages around 7 million daltons. To put that into perspective, the average mass of one molecule of water is 18 daltons.
Both molecular size and the molecular structure of HA regularly crop up in skincare marketing, so we’ll return to these properties later.
What is hyaluronic acid derived from?
As HuffPost points out in their skincare glossary, HA is almost overwhelmingly created synthetically for use in skincare products, along with medical and cosmeceutical applications. Traditionally, HA was extracted from rooster combs, but it’s now mainly produced via microbial fermentation in a process that has lower production and environmental costs [1].
Most companies can therefore follow the lead of The Ordinary and tout that their HA products are vegan. I did find one skincare company’s blog post expressing horror that synthetic, vegan HA is produced using streptococci bacteria.
Here is not the place to delve into much detail, but this is nothing more than scaremongering. Bacteria, including streptococci, are widely used in the pharmaceutical industry to produce antibiotics, vaccines and medically-useful enzymes, and the fact that these processes are also used in the production of skincare ingredients isn’t cause for alarm [2].
What does hyaluronic acid do in our skin?
To understand how HA hydrates our skin, we need to understand a bit about the skin’s physiology and its water content. Surprisingly, if you delve into the literature, it seems that the underlying mechanisms of skin hydration have yet to be fully elucidated [3]. However, dermatologists do have an in-depth understanding of the layers of our skin and its barrier function.
Our skin has four distinguishable layers: the stratum corneum (SC), the epidermis, the dermis and subcutaneous connective tissue [4]. Dermatologists define skin hydration as the water content of the epidermis and the dermis. However, it’s the SC, the outermost protective layer of our skin, which primarily regulates the ability of our skin to retain water [5]. The SC prevents transepidermal water loss, the loss of skin moisture to the external environment by evaporation. It’s more of a cellular matrix than an impenetrable barrier, and the intercellular spaces in the SC are enriched with lipids (skin’s natural fats, which include cholesterol and ceramides).
It’s well established that skin hydration levels depend on several factors, including the presence of HA in the epidermis and the dermis and the ordered arrangement of the lipids in the SC [6]. But what isn’t so clear is how water gets into the epidermis in the first place. “How water levels are achieved and maintained in the skin has not been a primary focus for dermatologists”, states one paper, and so the research into moisture diffusion pathways through skin layers is still ongoing [3].
Returning to what we do know, many beauty sites and skincare companies correctly state that HA naturally occurs in our skin. The Ordinary also adds this comment: “Note: Hyaluronic Acid is found in the skin naturally but its natural function within the skin is not hydration”, without any further explanation (as if the consumer wasn’t already bamboozled enough). What the copywriters mean is open to interpretation, but having learned that HA helps promote our skin’s barrier function, I’m inclined to disagree.
How does hyaluronic acid work in skincare?
HA has been lauded as an anti-ager and hydrator extraordinaire. Even science-grounded explainer articles aren’t short on the hyperbole. HuffPost’s explainer on HA is subtitled “Why It May Be Your Dry Skin Saviour” and Byrdie’s guide espouses that “the reason the beauty industry loves it so much lies in its seemingly magical ability to retain moisture.”
Magical might be a step too far, but it is true that HA is an excellent humectant, which is a substance that attracts and maintains moisture. Humectants enhance water absorption from the dermis into the epidermis, and in humid conditions they also help the SC to absorb water from the external environment. However, as you may have been cautioned online, this property makes them a double-edged sword in dryer environments. By drawing water from the dermis into the epidermis, they can enhance transepidermal water loss [7]. For this reason, humectants are almost always combined with an occlusive agent, like silicones, fatty acids, fatty alcohols and waxes. Take note, people — many simple HA serums lack occlusive ingredients, so follow with a moisturiser.
So HA can hydrate, but it is anti-aging? Skin aging is complicated, but it is well established that one of the characteristics of youthful skin is its ability to retain water [8], and HA is a key molecule involved in maintaining skin hydration. Furthermore, as we age, the amount of HA in the skin decreases.
An article published in The Journal of Clinical and Aesthetic Dermatology in 2014 enthuses: “Hyaluronic acid is said to be an ultimate solution for moisture retention of the skin” [9] (perhaps those beauty blogs aren’t too far off the mark with their praise). The 2014 study goes on to evaluate the efficacy of a HA preparation in treating wrinkles, skin hydration, and skin elasticity in humans, with measurable results:
“[The HA preparation] clearly demonstrated a significant benefit in decreasing the depth of wrinkles (up to 40%), and skin hydration (up to 96%) and skin firmness and elasticity were significantly enhanced (up to 55%) at the end of eight weeks.”
A 2016 study on a HA preparation known as HA5 was similarly impressive [8]:
“…HA5 instantly improves the appearance of fine lines/wrinkles and skin hydration. Subjects that continue using HA5 (for 8 weeks) demonstrated significant improvements in fine lines/wrinkles, tactile roughness, and skin hydration.”
Molecular size: a weighty issue
Earlier, I described HA as a very large molecule: very large indeed. HA used in topical anti-ageing preparations typically has a size of 3,000 nm in diameter [9]. However, the intercellular spaces in the stratum corneum are only 15 to 50 nm in size [4]. There’s just no way that HA of such a high molecular weight can penetrate to the epidermis or dermis — although this doesn’t mean that HA serves no function on the top layer of our skin. This 2016 paper published in Skin Research and Technology states that:
“HA, especially of high molecular weight, hydrates the skin by forming a film on the skin surface and preventing water loss. Whereas, low molecular weight HA can penetrate skin to protect and support the epidermal hydration, to moisturize the stratum corneum continuously to assure high quality of the epidermal texture [10].”
So can you put a number on how low the molecular weight of HA needs to be? Some papers show high skin penetration rates with HA of a molecular weight of 50 kDa — but this is somewhat controversial. Other studies suggest that most compounds with a molecular weight greater than 500 daltons cannot penetrate skin [10]. However, researchers are now using state-of-the-art microscopy and spectroscopy techniques to evaluate the permeation of active ingredients in the skin layers, and a study did find that HA of low molecular weight (20–300 kDa) did indeed pass through the stratum corneum, while high molecular weight HA (1000–1400 kDa) did not [6].
Let’s go back to that descriptor of The Ordinary’s serum, which boasts of combining low-, medium- and high-molecular weight HA. It’s true that the molecular size of HA determines its depth of delivery in the skin, so assuming the constituents are correctly described, the serum is capable of both preventing moisture loss on the skin’s barrier and penetrating to support epidermal hydration. Hydration assured!
But what about the statement that “HA can attract up to 1,000 times its weight in water”? And that next-generation crosspolymer — what’s that all about? To explore those claims in more detail, we’ll need to delve into some polymer engineering.
6L of water in each gram — really?
HA is one of the most hygroscopic molecules in nature, which means it is incredibly effective at absorbing moisture. That statement that HA can attract and hold up to 1,000 times its weight in water turns up here, here and well, everywhere.
Another claim you’ll often read is that 1g of HA can hold 6L of water [9]. Tracing a path of journal citations led me to a 1998 article by Sutherland about the applications of microbial polysaccharides — of which HA is one [11]. Sutherland’s article has a subsection dedicated to HA and states:
“A unique property of the polymer, its high water-binding and water-retention capacity, also results in its inclusion in many cosmetic preparations.”
This guy had his finger on the pulse of future skincare trends. The author goes on to say:
“The water-binding capacity correlates with the molecular mass and can be up to six litres of water per gram of polysaccharide.”
That is a whole lot of water, and Sutherland doesn’t provide any reference to where he gets this figure from. I can postulate that it was probably obtained from an experiment to test the swelling capacity of the HA polymer, which determines the amount of water that the polymer can absorb. Swelling capacity is described by this ratio: change in weight of polymer (due to swelling)/weight before swelling.
I wasn’t able to find any literature on the swelling ratio of HA used in cosmetics, but in pharmaceutical HA the swelling ratio can range from 20 to greater than 8,000 [12]. Sutherland’s claim of 1g of HA absorbing 6L of water suggests a swelling ratio of 6,000, which is very plausible.
Take a closer look at the statement: “the water-binding capacity correlates with the molecular mass”. We read before that companies boast about their low molecular weight HA and its skin-penetration properties. But there could in fact be a trade-off between penetration and water-binding capacity: the lower you go in terms of molecular weight, the lower the water-binding capacity. Some trials of low molecular weight HA are positive [9], while another study comparing different molecular weights of HA found that high molecular HA performed better than low molecular weight HA (which actually increased transepidermal water loss [13]).
If you’re interested in the exact molecular weight of the HA used in your serum, you’re out of luck, as it’s not something that cosmetic companies disclose to consumers. So all we have to rely on is the marketing copy, I’m afraid.
To add a further confounding layer, I recently came across an article suggesting that low molecular weight HA in skincare can cause inflammation, based on biochemical studies on tumours and wounds, as well as anecdotal evidence from some respectable dermatologists. So should we be avoiding or seeking out low molecular HA? The jury is out, and by this point, I am ready to throw something large and heavy at anyone who claims that skincare isn’t rocket science.
How much hyaluronic acid is in your serum?
Funnily enough, you might not find HA on the ingredients list at all! The Ordinary’s serum doesn’t actually contain HA, and neither does its more expensive sister product, Hylamide, nor even Dr Barbara Sturm’s $450+ version. Instead, they contain sodium hyaluronate, which is the sodium salt form of HA.
The Ordinary’s product description draws attention to the use of a “next-generation HA crosspolymer”, which presumably means they use a cross-linked form of sodium hyaluronate. Cross-links are bonds that link one polymer chain to another and can be produced by various methods of chemical synthesis. There are a few studies that show either improved skin penetration or improved skin hydration using cross-linked HA (rather than HA with a conventional linear structure) [13, 14], so The Ordinary might be on to something here.
Stacked Skincare, which sells its Hyaluronic Acid Hydrating Serum for a cool $130, is another contender that uses sodium hyaluronate, rather than HA. The product info on their website claims: “Sodium hyaluronate is a more expensive salt form of hyaluronic acid that has a low molecular weight and sinks in more effectively than regular HA.”
In actual fact, sodium hyaluronate is considerably less expensive than HA, which is partly why it shows up in more products. Sodium hyaluronate may have a smaller molecular size than HA, which would allow it to penetrate deeper into the skin, but it may not be smaller in size than low molecular weight HA (and as we discussed before, penetration isn’t everything). Stacked Skincare gets a gold star for disingenuous marketing.
So how much HA or sodium hyaluronate is efficacious in skincare? One study evaluating creams containing only 0.1% HA showed significant improvement in skin hydration and wrinkle reduction [6]. But I wasn’t able to find any published literature evaluating the topical application of sodium hyaluronate in terms of skin hydration, so I can’t provide a recommendation for a concentration to look for. Byrdie points out that the industry standard is a 1–2% concentration of sodium hyaluronate in a solution that’s primarily composed of water. Nevertheless, you won’t find many brands apart from The Ordinary publicising how much HA/sodium hyaluronate is in their serums.
In their article, Byrdie interviews Stacked Skincare founder Kerry Benjamin, who has this warning about high concentrations of sodium hyaluronate to share:
“Benjamin claims that if the solution has more than 4% sodium hyaluronate, it can actually dry your skin out. She illustrates this with an analogy: If you put too much salt on a sponge, the salt will pull water out of the sponge and dry it out. In the same way, since sodium hyaluronate is a salt rock, too much of it can draw moisture away from the skin, Benjamin claims. She says that 2% is the highest concentration of hyaluronic acid you can put in a solution without any drying effects.”
I haven’t found anything in published literature to support these statements. But then, people who sell cosmetics or perform facials have a habit of sounding very confident that they understand how products work — a lot more confident than researchers in dermatology (scientists are notoriously conservative about making conclusions).
However, I suspect that you are unlikely to find serums with HA concentrations higher than 2% for aesthetic reasons. DIY chemists (such as Humblebee and Me) who’ve experimented with creating their own serums out of sodium hyaluronate report that even a low molecular weight 1% solution is fairly viscous, so I suspect that cosmetic companies keep their concentrations low to keep the texture of the serum appealing, as well as keep costs down.
Selling science
After this deep dive into HA serums, it strikes me that the product info that consumers ingest mostly isn’t incorrect (Stacked Skincare’s aside) or misleading, so much as irrelevant to the buyer.
Is it really useful to your dermis to learn that a well-engineered HA molecule can retain 6L of water? For one, it’s highly unlikely that skincare companies are using this high molecular weight HA, and the majority of serums use sodium hyaluronate rather than HA anyway.
It’s merely an impressive statement. It’s much more impressive than simply describing HA as a great water-binding ingredient, like the inexpensive glycerine (AKA “the most underrated skincare ingredient”). Or describing it as a good topical treatment to enhance the skin’s barrier function — as are ceramides, liquorice extracts and the much-maligned dimethicone (a silicone) and petrolatum (mineral oil) [15]. HA is undoubtedly an excellent skincare ingredient, but there are less expensive, less overhyped alternatives if you’re looking for hydration.
Skincare companies are increasingly using science-y descriptions to sell their products as a well thought-out marketing tactic. They’re credible because they reference scientific literature. They’re refreshing after almost a century of reading advertisements for creams that “beautify the complexion instantly”. They’re catnip to an audience that is both weary of unproven claims and better educated about cosmetic chemistry.
The Ordinary is proof of the efficacy of selling science. The CEO and co-founder of parent company DECIEM, Nicola Kilner, attributes its success to tapping into consumers’ desires: “They no longer want to just believe in hocus-pocus potions. They want to actually understand what ingredients they’re using at what percentage.”
Agreed — but do the people selling the potions understand them any better?
References
1. Liu, L., et al., Microbial production of hyaluronic acid: current state, challenges, and perspectives. Microbial cell factories, 2011. 10: p. 99–99.
2. Todar, K., Overview of Bacteriology, in Todar’s Online Textbook of Bacteriology. 2012. p. 6–12.
3. Draelos, Z., Aquaporins: an introduction to a key factor in the mechanism of skin hydration. J Clin Aesthet Dermatol, 2012. 5(7): p. 53–6.
4. Desai, P., R.R. Patlolla, and M. Singh, Interaction of nanoparticles and cell-penetrating peptides with skin for transdermal drug delivery. Molecular membrane biology, 2010. 27(7): p. 247–259.
5. Guzman-Aonso, M. and T.M. Cortazar, Water content at different skin depths and the influence of moisturizing formulations. Household and Personal Care Today, 2016. 11(1): p. 35–40.
6. Pavicic, T., et al., Efficacy of cream-based novel formulations of hyaluronic acid of different molecular weights in anti-wrinkle treatment. J Drugs Dermatol, 2011. 10(9): p. 990–1000.
7. Kraft, J.N. and C.W. Lynde, Moisturizers: what they are and a practical approach to product selection. Skin Therapy Lett, 2005. 10(5): p. 1–8.
8. Narurkar, V.A., et al., Rejuvenating Hydrator: Restoring Epidermal Hyaluronic Acid Homeostasis With Instant Benefits. J Drugs Dermatol, 2016. 15(1 Suppl 2): p. s24–37.
9. Jegasothy, S.M., V. Zabolotniaia, and S. Bielfeldt, Efficacy of a New Topical Nano-hyaluronic Acid in Humans. The Journal of clinical and aesthetic dermatology, 2014. 7(3): p. 27–29.
10. Essendoubi, M., et al., Human skin penetration of hyaluronic acid of different molecular weights as probed by Raman spectroscopy. Skin Res Technol, 2016. 22(1): p. 55–62.
11. Sutherland, I.W., Novel and established applications of microbial polysaccharides. Trends Biotechnol, 1998. 16(1): p. 41–6.
12. Balazs, E.A. and A. Leshchiner, Cross-linked gels of hyaluronic acid and products containing such gels. 1985, Genzyme Biosurgery Corp: United States.
13. Sundaram, H., et al., Pilot Comparative Study of the Topical Action of a Novel, Crosslinked Resilient Hyaluronic Acid on Skin Hydration and Barrier Function in a Dynamic, Three-Dimensional Human Explant Model. J Drugs Dermatol, 2016. 15(4): p. 434–41.
14. Berkó, S., et al., Advantages of cross-linked versus linear hyaluronic acid for semisolid skin delivery systems. European Polymer Journal, 2013. 49(9): p. 2511–2517.
15. Draelos, Z.D., New treatments for restoring impaired epidermal barrier permeability: Skin barrier repair creams. Clinics in Dermatology, 2012. 30(3): p. 345–348.
