Hydroxy Acids

Based on a presentation by Glynis Ablon, MD, FAAD

Watch the video of this Skincare Academy presentation featuring Dr. Ablon at https://jcad.tv/sca-glynis-ablon-hydroxy-acids/

Dr. Ablon is Associate Clinical Professor of Dermatology at UCLA and Director of the Ablon Skin Institute and Research Center in Manhattan Beach, California. 

In ancient times, the Egyptians (e.g., Cleopatra) bathed in sour milk because it made the skin smooth and silky due to an alpha hydroxy acid called lactic acid present in the sour milk. Egyptians and Greeks applied face masks made from crushed grapes, which contained tartaric acid, for a glowing complexion. In the 1880s, German dermatologist Unna experimented with chemical peels, such as salicylic acid, as well as trichloroacetic acid, resorcinol, and phenol, which is now called Unna paste and is something I still use today. In the early 1940s, New York dermatologist Eller worked with salicylic acid, resorcinol, and CO2 slush. In the 1970s, Van Scott and Yu found that topical hydroxy acids improved hyperkeratinization, detaching the hyperkeratotic stratum corneum. This allowed for improvements in ichthyosis, dry skin, warts, and acne. In 1989, dermatologist Gary Monheit worked with salicylic acid, resorcinol, and lactic acid, followed by trichloroacetic acid, with great results. In 1995,  dermatologist Bruce Katz worked with alpha hydroxy acid and 5-fluorouracil. 

Traditionally, we know that hydroxy acids cause chemical exfoliation of the epidermis, aiding in achieving a smooth, glowing complexion. Additionally, we’re finding that newer generation hydroxy acids increase hydration, affect collagen stimulation, act as antioxidants, aid in skin barrier repair, block matrix metalloproteinases and elastases, and rejuvenate the skin.  

Alpha hydroxy acids. Alpha hydroxy acids (AHA) are the shortest chain of acid. Alpha hydroxy acids, also known as fruit acids, include glycolic acid, lactic acid, mandelic acid, malic acid, and citric acid. Not all of these are antioxidants, but malic and citric acid are. Glycolic and lactic acids are the most common acids found in skincare. AHA is water soluble, but not fat soluble, and you do need to neutralize with water or sodium bicarbonate. When using full-strength glycolic acid, which is about 70%, epidermolysis occurs in 3 to 7 minutes. Therefore, it’s important to set a timer and watch the skin and neutralize. With full-strength lactic acid 70%, you will see slower epidermolysis; 5% to 20% concentrations of lactic acid cause corneocyte detachment and desquamation of the lower newly forming stratum corneum.

In an in-vitro study in 2003 on melanoma cells, glycolic acid and lactic acid showed tyrosinase inhibition, demonstrating that these acids do more than just smooth the skin. The longest chain derivative of glycolic acid is mandelic acid, derived from bitter almonds. Mandelic acid has a phenyl side chain that increases its lipophilicity, which can help target oily and acne-prone skin more effectively than the water-soluble AHAs.

Glycolic acid (see Table) can accelerate collagen synthesis by fibroblasts, and it is thought to be modulated by keratinocytes producing cytokines. Interleukin 1a is one of the primary mediators regulating the matrix degeneration that is released from the keratinocytes after glycolic acid treatment. AHAs also decrease the calcium gradient in the epidermis; this can stimulate lamellar body production as well as chelate calcium ions to disrupt the desmosomes and the adherent junctions, which allows for cell shedding. 

In a study in which sun-damaged forearm skin was treated with 20% glycolic acid lotion versus vehicle twice daily for three months, increased epidermal thickness was observed, in addition to increased epidermal and dermal hyaluronic acid and increased collagen gene expression. (Burge S. Br J Dermatol. 1994;131(2):153–159.)

Factors that affect the penetration of glycolic acid in the skin include acid concentration, pH bioavailability, amount of buffering, type of formulation (gel, liquid, cream), frequency of application (no more than weekly is recommended), volume of acid applied to the skin, and duration of time the acid remains on the skin.

Salicylic acid. Salicylic acid is considered a part of the beta hydroxy family, but it is not a true beta hydroxy acid; it is an aromated hydroxy acid. True beta hydroxy acids are made from beta hydroxybutanoic acid, which is from urine; it is found in plants and is present in the body, but we do not use it in skincare. Salicylic acid is regarded as a BHA because it has an attachment at the beta position; the benzene ring is attached to the carboxyl and hydroxyl group. Salicylic acid is keratolytic, exfoliating, and fat soluble. Therefore, it is useful in individuals with oily skin and it can penetrate the pores. Salicylic acid is included in the Food and Drug Administration (FDA) monograph for acne in concentrations between 0.5% and 2%. It is also included in the FDA monograph for dandruff, seborrheic dermatitis, and psoriasis in concentrations ranging from 1.8% to 3%. Higher concentrations of salicylic acid (20–30%) can be used to improve acne and postinflammatory hyperpigmentation. Because salicylic acid is derived from willow bark, from which aspirin is also derived, it is anti-inflammatory. Of note, using too much over the entire body brings with it the risk of salicylate poisoning, but this is very uncommon. 

Beta lipohydroxy acids. Beta lipohydroxy acids were developed in the 1980s. They are a derivative of salicylic acid and are oil soluble. Their larger molecules make for slower skin penetration and cell-by-cell exfoliation. This leads to gentler exfoliation, improved tolerability, and comedolytic properties that make it great for treating acne. Beta lipohydroxy acids are found in many skincare products for acne and anti-aging, due to its ability to stimulate glycosaminoglycans, collagen, and elastin, which leads to dermal thickening. 

Polyhydroxy acids. Polyhydroxy acids (PHAs) are the next generation of alpha hydroxy acids. Gluconolactone is the most used PHA in skincare. It’s a larger molecule and used commonly in skincare for sensitive skin since it’s gentler than other acids. Gluconolactone is good for skin barrier strengthening as well as skin hydration, since it attracts water. Gluconolactone is an antioxidant, so it helps protect the skin from UV radiation, pollution, and free radical damage. It’s a stable molecule, so it can be formulated with different oxidative drugs, such as benzoyl peroxide. It reduces advanced glycation end products (AGEs), which reduce skin elasticity. 

Bionic acids. Bionic acids are basically PHAs attached to a sugar molecule, so they also have antioxidant effects and reduce AGEs. They have skin protecting and hydrating effects, as well as chelating benefits. They are used in solutions that preserve transplanted organs and can chelate iron to inhibit hydroxyl radical production. Bionic acids are being studied for their possible prebiotic and antimicrobial properties. Bionic acids inhibit matrix metalloproteinase enzymes. 


In summary, hydroxy acids are superficial peeling agents with high safety records and little risk of complications, but of course we want to ensure that we explain all risks to our patients. Multiple peeling sessions are needed for effectiveness. There is little to no downtime depending on the concentrations, and they are safe to use on all skin types. They can also be used to amplify other topicals or procedures, including other chemical peels. Combination therapy is still most effective. I use peels in conjunction with topical home care, lightning agents, and prescription medication. I also use them prior to laser procedures, to improve the penetration of the laser. They can be used to improve absorption of photodynamic therapy agents. I always ask my patients about a history of herpes simplex on the face, and we premedicate our patients and provide instruction sheets for care after the procedure. Hydroxy acids are a nice option for young clientele who are inexperienced in the aesthetic world but would like to try something gentle that will improve their skin.