α-Hydroxy Acids

Structure

AHA are weak organic acids, chemically distinguished by one or more hydroxyl group covalently bonded to the α-carbon of a carboxylic acid. This structure accounts for the water-soluble, or hydrophilic, properties of AHA. The smallest of the AHA are the monocarboxylic acids—glycolic (2-hyxroxyethanoic acid), lactic (2-hydroxy-propanoic acid), and mandelic acid (2-hydroxy-2-phenylethanoic acid). Glycolic acid is the 2-carbon molecule that conforms to the formula HOCH ₂ COOH ( Fig. 52.1 ). The advantages of glycolic acid are that it is stable, colorless, odorless, water-soluble, and nontoxic if ingested. Lactic acid, has a 3-carbon chain; the formula is shown in Fig. 52.1 . Lactic acid can exist in several isomeric forms: the L (+) (levorotatory), the D (−) (dextrorotatory), or the dl racemic mixture. The L (+) for is the naturally occurring isomer, while the D (−) and racemic mixture can be produced through fermentation by certain bacterial strains. The two types have been shown to have equal effectiveness. Additional subcategories of AHA include dicarcoxylic acids (malic and tartaric acid) and tricarboxylic acids (citric acid), which are larger with longer carbon chains. Higher molecular weight AHA (malic acid, citric acid, mandelic acid, tartaric acid) do not penetrate the stratum corneum as well as lower molecular weight AHA (glycolic and lactic acid).

PHA are longer carboxylic acids with two or more hydroxyl groups, one of which must be attached to the α position. Owing to their larger size, PHA have a slower rate of absorption into the skin. The principal PHA are gluconolactone, galactose, and lactobionic acid. Galactose and gluconolactone contain four hydroxyl groups each, and lactobionic acid contains eight hydroxyl groups, allowing them to bind more water than the smaller AHA.

ß-Hydroxy acids (BHA) are carboxylic acids having one hydroxyl group attached to the ß-position of the carboxyl group. Some BHA are actually considered AHA as they also contain a hydroxyl group at the α-position, including citric acid and malic acid. Salicylic acid is sometimes incorrectly characterized as a BHA. This is because the hydroxyl group is attached to an aromatic phenol group, rendering the hydroxyl group acidic rather than neutral as in BHA. This chapter will not discuss BHA or salicylic acid extensively, but it is important to note that salicylic acid is lipophilic and able to penetrate into sebum-rich areas of the pores, making them a useful treatment in conditions like acne.

Mechanism of Action

Dermal Effects

Q52.1 With long-term use, the AHA produce measurable dermal changes ( Table 52.1 ). Dermal effects of AHA include increased dermal thickness, possibly because of fibroblast proliferation and increased collagen production. A controlled study using 25% glycolic, lactic, or citric acid to the forearm for 6 months showed an approximately 25% increase in skin thickness. Both the epidermis and papillary dermis were thicker without inflammation, with the dermis showing increased glycosaminoglycans (GAG), increased collagen density, disbursement of melanin, and improved quality of elastic fibers ( Fig. 52.2 ).

Table 52.1

Biologic Responses To Varying Α-Hydroxy Concentrations and pH

Modified from Van Scott EJ, Yu RJ. Actions of α hydroxy acids on skin compartments. J Geriatr Dermatol . 1995;3(Suppl3):19A–25A.

Stratum Corneum Response	Epidermal and Dermal Response
<10% AHA application daily with pH >3.0 Low pH with high AHA concentration in short exposure times (i.e., ‘office peels’)	Single exposure to high-concentration un-neutralized glycolic or lactic acid Repeated exposures to low AHA concentrations with pH <3.0 Repeated exposures to high AHA concentrations, pH >3.0 but less than neutral

AHA, α-Hydroxy acid.

Data suggests that glycolic acid produces a functional activation of fibroblasts. In a study designed to evaluate the effect of glycolic and malic acids on cultured dermal fibroblasts, results showed an increase in cell proliferation and collagen production in response to glycolic acid in a dose-dependent manner, but showed minimal change with malic acid or control. In another study, Okano and associates found that glycolic acid directly increased collagen synthesis by fibroblasts, and regulated matrix degradation and collagen production through keratinocyte-released cytokines. The increase in type I collagen and intercellular ground substances (namely hyaluronic acid) leads to increased dermal hydration and thickness, and provides an aqueous environment for the diffusion of nutrients and toxins. For the treatment of photodamage, in addition to AHA effects on the epidermis mentioned above, AHA can also decrease the appearance of rhytides through these effects on the dermis.