INTRODUCTION
Hydroxy acids (HAs) are a diverse class of topical agents with a decades-long tenure in dermatology, used for acne, ichthyosis, keratoses, warts, psoriasis, and photoaging. HAs are classified into alpha HAs (AHAs), beta HAs (BHAs), and polyhydroxy acids (PHAs). AHAs, introduced in the 1970s, promote cell turnover and collagen synthesis, while BHAs provide keratolytic, antimicrobial, and antiinflammatory benefits. PHAs, a newer generation HA, offer similar effects to AHAs with added humectant properties and less irritation. HAs are formulated in low concentrations for over-the-counter (OTC) skincare, and higher concentrations for prescription chemical peels.1 Given their long-standing and widespread use, dermatologists must understand their nuances to optimize treatment recommendations and patient safety.
Chemical Structure and Properties
HAs are classified by the position of their hydroxyl (-OH) group relative to their carboxyl (-COOH) group, influencing solubility, penetration, and biological activity. AHAs and BHAs are carboxylic acids with a hydroxyl group at the α-position and β-position, respectively. PHAs contain two or more hydroxyl groups, including at least one in the α-position (Figure 1).1
Chemical Structure and Properties
HAs are classified by the position of their hydroxyl (-OH) group relative to their carboxyl (-COOH) group, influencing solubility, penetration, and biological activity. AHAs and BHAs are carboxylic acids with a hydroxyl group at the α-position and β-position, respectively. PHAs contain two or more hydroxyl groups, including at least one in the α-position (Figure 1).1
Low molecular weight AHAs, such as glycolic acid (GA) and lactic acid (LA), penetrate the skin most effectively, whereas larger AHAs, like tartaric and mandelic acid (MA), offer milder exfoliation with less irritation. Most AHAs are water-soluble, though lipophilic AHAs like MA better penetrate the skin.2,3 Salicylic acid (SA), the most wellknown BHA, is technically misclassified as such due to structural and functional differences. Being lipid-soluble, BHAs penetrate sebaceous follicles, while PHAs' increased molecular size limits deeper penetration. Gluconolactone, a PHA, metabolizes into an AHA, possessing similar benefits to AHAs while also acting as a humectant and antioxidant.1,4
Mechanisms of Action
AHAs promote exfoliation by disrupting cellular adhesions within the epidermis, likely through calcium ion chelation, weakening intercellular adhesion and facilitating desquamation. In vitro and ex vivo investigations demonstrate GA's role in enhancing collagen synthesis, modulating matrix degradation, increasing epidermal thickness, and upregulating hyaluronic acid production. LA has been shown to increase vascular endothelial growth factor and contribute to wound healing. Both GA and LA accelerate epidermal turnover and inhibit tyrosinase, improving superficial pigmented lesions. PHAs offer skin-smoothing, anti-aging, and moisturizing effects without skin irritation, while gluconolactone has demonstrated photoprotective properties.1
SA, a keratolytic, possesses photoprotective and antimicrobial properties. Both animal and human studies have shown SA can lessen ultraviolet penetration, while preclinical studies showed its ability to modulate and downregulate bacterial virulence factors. β-lipohydroxy acid, an SA derivative, exhibits antibacterial, antifungal, anti-inflammatory, and anti-comedogenic activity.1
Clinical Applications
HAs are widely used to treat various dermatologic conditions. GA is effective for hyperpigmentation, including post-inflammatory hyperpigmentation (PIH), melasma, and sun-induced discoloration. While GA aids in acne treatment through exfoliation, SA’s antiinflammatory and antimicrobial properties make it particularly
Mechanisms of Action
AHAs promote exfoliation by disrupting cellular adhesions within the epidermis, likely through calcium ion chelation, weakening intercellular adhesion and facilitating desquamation. In vitro and ex vivo investigations demonstrate GA's role in enhancing collagen synthesis, modulating matrix degradation, increasing epidermal thickness, and upregulating hyaluronic acid production. LA has been shown to increase vascular endothelial growth factor and contribute to wound healing. Both GA and LA accelerate epidermal turnover and inhibit tyrosinase, improving superficial pigmented lesions. PHAs offer skin-smoothing, anti-aging, and moisturizing effects without skin irritation, while gluconolactone has demonstrated photoprotective properties.1
SA, a keratolytic, possesses photoprotective and antimicrobial properties. Both animal and human studies have shown SA can lessen ultraviolet penetration, while preclinical studies showed its ability to modulate and downregulate bacterial virulence factors. β-lipohydroxy acid, an SA derivative, exhibits antibacterial, antifungal, anti-inflammatory, and anti-comedogenic activity.1
Clinical Applications
HAs are widely used to treat various dermatologic conditions. GA is effective for hyperpigmentation, including post-inflammatory hyperpigmentation (PIH), melasma, and sun-induced discoloration. While GA aids in acne treatment through exfoliation, SA’s antiinflammatory and antimicrobial properties make it particularly
