Yesterday, in What are Hydroxy Acids?, we differentiated the various types of hydroxy acids (HAs) that one can encounter in the cosmetic and medical industries. I proceeded to enumerate 10+ examples of compounds that fall under the umbrella definition given for HAs. Fortunately for the readers, or those of you who are bored by pages of scientific jargon, only a few of the examples have been widely used to treat skin conditions. The FOUR that will be covered today include the following:
- (1x) Alpha Hydroxy Acid (AHA): Glycolic Acid (GA).
- (2x) Salicylic Acid Family (SAF): Salicylic Acid (SA), and Lipohydroxy Acid (LHA).
- (1x) Polyhydroxy Acid (PHA): Gluconolactone (GUL).
As the most well-known and studied HA, you always hear that GA is great for “exfoliating” the skin. But how does it exfoliate the skin? Several studies suggest that GA exfoliates the skin by manipulating the calcium ion concentrations present in the epidermis. Calcium ions play crucial roles in the adhesion of skin cells, specifically in structures like the desmosomes and adheren junctions. Now, because AHAs like GA can chelate metal ions, its presence once applied topically, will result in an overall loss of the epidermal concentration of calcium ions, which in turn will disrupt the adhesion of skin cells, ultimately leading to “forced” exfoliation.
*Note that because GA is extremely hydrophilic, it will tend to stay away from, and therefore not exfoliate areas that are lipid-rich, like the lining of hair follicles (pores).
What about GA’s alleged claims of helping with anti-aging and hyperpigmentation? Fortunately, GA is a powerhouse when it comes to these issues as well; it addresses them via multiple pathways.
- In vitro and ex vivo studies indicate that high-strength GA directly accelerates collagen synthesis in fibroblasts by modulating activation.
- Furthermore, GA inhibits matrix degradation by stimulating the production of the cytokine, interleukin-1 alpha (IL-1a). Because IL-1a also plays significant roles in other biological interactions including prostaglandin release (compounds related to inflammatory reactions), that may attribute to GA’s irritation potential, overly aggressive and chronic use of GA is not recommended.
- GA can also increase epidermal thickness, epidermal and dermal levels of hyaluronic acid (the other HA!), and increased type I collagen gene expression measured by the levels of mRNA. The results are positive changes in appearance, texture, and function.
- Finally, GA is known to be effective in treating forms of hyperpigmentation such as melasma and solar lentigos. However, in the past it was just assumed that this mechanism of action was due to accelerated remodeling and exfoliation, which will result in faster pigment dispersion. However, some studies have shown that part of GA’s ability to reduce hyperpigmentation is independent from its acidic characteristic. In fact, GA was shown to directly inhibit the tyrosinase enzyme. While several compounds such as hydroquinone already operate via this mechanism, why not use GA if it has so many other benefits?
Another very well-known HA, SA is known for its ability to treat acne. It does so in a similar fashion as that of GA. However, with the hydroxyl and carboxyl groups attached directly the benzene ring, SA is much more lipophilic than GA. Therefore, it can exfoliate the areas (like in the pores), that GA can’t. However, it does have distinct properties that separate it from GA.
- SA is antibacterial, which has the potential to neutralize any P. Acnes that’s present in acne papules and pustules. SA’s antibacterial nature comes from its ability to inhibit the production of various aspects necessary for binary fission (bacterial reproduction), such as fibrinogen, fibronectin, and alpha-hemolysis.
- SA is also anti-inflammatory, which again is great for treating acne conditions, as any additional inflammation will worsen the breakouts. SA’s anti-inflammatory nature comes from its ability to truncate the arachidonic acid (AA) cascade. This in part, allows SA to suppress the expression of inflammation-inducing genes by the inhibition of transcription activators such as (nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), activation protein-1 (AP-1), and CCAAT/enhancer-binding protein B (C/EBPB), in case you were curious…
A newcomer and relative to SA, lipohydroxy acid (LHA) is structurally characterized as an SA molecule that has an eight-carbon fatty chain connected to the aromatic benzene ring. This “attachment” allows for LHA to be more lipophilic than SA, while penetrating less deeply, which may partially account for its lower irritation potential. Due to this structural modification, LHA appears to modulate trans-membrane glycoproteins and not affect the corneocyte membrane, unlike SA and others, which allows LHA to induce desquamation of individual desmosomes, resulting in cleaner and more even exfoliation.
With exfoliation covered, what else can this newcomer do? Besides being anti-bacterial and anti-inflammatory like its parent molecule SA, LHA’s other important characteristic is that it exhibits similar effects as those of tretinoin, albeit less potent ones. LHA has been shown to stimulate renewal of epidermal cells and of the extracellular matrix.
While a relatively new compound, LHA is an exciting ingredient that I would personally love to see further researched and elucidated. Its low irritation potential (by being less penetrating and the ability to operate at a pH of 5.5) combined with its (weak) tretinoin-like effects, would be a Godsend for those who have very sensitive skin (like people with rosacea) and cannot use, but still desire the benefits of LHA’s more traditional and irritating counterparts.
*Note that most if not all of the studies cited for LHA are done by L’Oreal Corp, or some affiliated party. L’Oreal owns the sole brand that uses LHA, LaRoche Posay. And while the studies are well-designed and the conclusions are logical, this conflict of interest and source of bias cannot be overlooked. Guess we can only wait until more independent research arises.
As stated last week, polyhydroxy acids (PHAs) are AHAs with multiple hydroxyl groups. Even newer than LHA, PHAs represent a new generation (though not necessarily a better one) of HAs because they give similar results as AHAs, without the irritation that usually comes hand-in-hand.
Furthermore, PHAs like gluconolactone (GUL) provide additional hydration due to the additional hydroxyl groups, which can attract more water as humectants. GUL has also been shown to work well with other proven ingredients such as tretinoin and hydroquinone.
I also find it exciting that gluconolactone has been shown to be just as effective as benzoyl peroxide (BP) at reducing acne lesions, without the irritation! That’s great because if you can avoid BP, which operates by generating ROS and ages the skin prematurely, you can deal with acne without hurting your skin. Once again, I’m eager to see more well-designed studies done to examine and analyze the currently unknown mechanism of action and any other potential dermatologic applications.
Phew! While that wasn’t very long, it admittedly was quite technical. Stay tuned for Part 3 (misconceptions of HAs), and let me know your opinions in the comments section!
Contributing author: John Su
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