Exfoliants, Moisturizers and More: AHAs, BHAs, and PHAs

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Chapter 16 Exfoliants, Moisturizers and More: AHAs, BHAs, and PHAs

INTRODUCTION

Exfoliation is defined from the Latin exfoliatio meaning falling off in scales or layers. Since many dermatologic conditions are either due to or associated with an inability to exfoliate owing to excessive corneocyte cohesion, it appears that chemical exfoliation of some epidermal elements would provide a therapeutic benefit. In addition, this accelerated cell loss and sloughing which is the basis of chemexfoliation has been found to beneficially impact the skin’s appearance. These cosmetic benefits attributed to skin exfoliation have been known since the time of the ancient Egyptians, when their observation that simply bathing in sour milk, now known to contain the bioactive ingredient lactic acid, yielded softer and smoother skin, thereby improving the skin’s luster and appearance. Dermatologists have been interested in chemical exfoliants since 1882 when Unna, a German dermatologist, first described the properties of salicylic acid, resorcinol, phenol, and trichloroacetic acid as a chemical peeling agent.

Nowadays, we have many means to induce skin exfoliation. These agents are chemical, mechanical, and thermal from lasers or light-based sources. This section will concentrate on those chemical agents known as AHAs (alpha hydroxy acids), BHAs (beta hydroxy acids), and PHAs (polyhydroxy acids) that have found a resurgence in their popularity for both the therapeutic as well as the cosmetic benefit that they impart to the skin. It has long been touted that their benefits are due to exfoliation alone. Currently then, the US Food and Drug Administration (FDA) classifies AHAs as a cosmeceutical for this and other superficial reactions on the skin.

Depending on their formulation, vehicle, acid type, pH, concentration, and body area treated, these acids can provide a wide range of skin benefits. There still is controversy surrounding these agents as well as others, which will be discussed in this chapter, along with the exfoliation process risk and benefit ratio to the skin.

ALPHA HYDROXY ACIDS (AHAs)

• Definition

AHAs are a group of organic carboxylic acids that have been popularized since they are felt to be natural substances. The name is derived from their chemistry—a hydroxyl group attached to the alpha carbon adjacent to the acid moiety. Indeed, many AHAs are found naturally occurring in the body, but when used in skin products or procedures these agents are synthetically derived. Nonetheless, synthetic AHAs function as those derived from organic sources.

The simplest molecule of AHAs and indeed the prototype is glycolic acid (derived from sugarcane), with the lowest molecular weight and a pKa of 3.83. It is water soluble and has been used in its partially neutralized form for topical home care products and in a free acid form in peeling products. Lactic acid (derived from sour milk), with a molecular weight of 91, is felt to work best in its L form. It has been found in topical home care products and in Jessner’s peeling solution. Tartaric acid (derived from grapes) is an antioxidant and is used in some home care products. Citric acid (derived from citrus fruits) is a larger change AHA but with similar skin benefits.

Less commonly used AHAs include mandelic acid (phenyl glycolic acid) and benzilic acid (diphenyl glycolic acid), which have increased lipophilic and hydrophilic properties when compared to more traditional AHAs. These properties enable them to be absorbed into sebaceous glands, where the potential exists to treat oily and acne-prone skin with greater benefit. The addition of mandelic acid and benzilic acid to 0.5% salicylic acid (SA) was shown to produce significant oil-reducing properties as well as a favorable tolerability profile with less discomfort than glycolic acid.

• Mechanism of action

The mechanism of action of AHAs has not been fully determined. It is postulated that AHAs act as a chelating agent and thereby decrease local calcium ion concentrations from cation-dependent cell adhesion molecules. This calcium loss from cadherins of desmosomes, adherens junctions and tight junctions causes a decrease in desmosomal attachments. This makes the usually protected endogenous stratum corneum chymotryptic enzymes on cadherins vulnerable to proteolysis. When calcium is decreased, cellular adhesions are disrupted and exfoliation takes place (Fig. 16.3).

Another proposed mechanism for AHA induced exfoliation is an increase in apoptosis. In one study, lactic acid (LA) was shown to cause a concentration-dependent increase in apoptotic cells. In this same study, vascular endothelial growth factor (VEGF) was increased at least 2.5-fold over vehicle control with either a 1.5 or 3% concentration of LA. Angiogenin secretion was decreased by LA in a concentration-dependent manner. It was concluded that topical AHAs modulate secretion of cytokines by keratinocytes and that this regulation may account in part for their effects in skin disorders as well as photoaging. Another study in 2003 confirms that glycolic acid (GA) directly accelerates collagen synthesis by fibroblasts and modulates matrix degradation and collagen synthesis through keratinocyte-released cytokines (Fig. 16.4). The primary mediator for this matrix degradation is interleukin 1α (IL-1α).

In our study of AHAs—GA, LA, and CA (citric acid) at a 25% concentration—it was shown that there was an increase in dermal dendrocytes and mast cell activation. It was postulated then that AHAs may cause upregulation of epidermal and dermal markers by stimulating transforming growth factor-beta (TGF-β) which in turn causes activation of dermal dendrocytes and mast cell release.

• Their role in skin barrier function

The major concern with long-term use of AHAs is the possibility of disruption of skin barrier function. Several studies have addressed this. In 1997, Berardesca et al applied to six test sites the following: three different AHAs (GA pH 4.4, LA pH 4.4, tartaric acid (TA) pH 3.4) and a PHA (gluconolactone (GLU) pH 4.3) all in 8% concentration, a vehicle (VE), and an untreated skin control (UNT) over 4 weeks. Each of these sites was then subjected to a 5% sodium lauryl sulfate (SLS) challenge patch test under occlusion for 6 hours. Barrier function and skin irritation were then evaluated immediately after removal of the SLS patches and at 24 and 48 hours later. There were no significant differences in the transepidermal water loss (TEWL) after AHAs and PHAs at week 4. The vehicle-treated site actually showed an increase in water loss compared with the untreated control. This was felt to be due to the vehicle being slightly alkaline at pH 8.2. After SLS challenge, GLU- and TA-treated sites resulted in a significantly lower water loss compared to VE, UNT, and GA at 24 and 48 hours. They concluded that all AHAs/PHAs can both improve barrier reactivity and increase resistance to surfactant-induced skin irritation. This effect was more marked, however, with gluconolactone- and tartaric acid-treated sites. This unique effect of GLU and TA was postulated to be due to their antioxidant properties.

In this study, the authors tried to explain the observation that AHAs and PHAs impart a brightening effect or glow to the appearance of the skin. This effect was postulated to be due to the thinner more compact stratum corneum after AHA/PHA treatment, which better reflects light. Surprisingly, this effect was found to be still present even after SLS challenge, a known inducer of lackluster, dry, scaly skin. It was concluded from the study that AHAs/PHAs impart a measurable skin brightening effect at about week 4 of treatment and, more importantly, they protected the skin from the aggressive challenge of surfactants.

In 2001, Kim et al applied a 5% GA and a 5% LA to hairless mice daily over a 2-week period. They found no significant difference in TEWL and skin capacitance when comparing the mice skin treated with the AHAs versus vehicle alone. They did find on electron microscopy that the AHA-treated skin showed an increase in the number and secretion of lamellar bodies and a decrease in stratum corneum layers compared to the epidermis of vehicle-treated skin alone. They concluded that the AHAs in low concentrations may improve skin barrier function in mice by inducing enhanced desquamation and an increase in the number and secretion of lamellar bodies without increasing TEWL. This may be a unique function of the AHAs, again explaining their exfoliating and moisturizing capabilities.

In 2004, Song et al found that skin barrier function is damaged after a GA peel and also after aluminum oxide microdermabrasion but recovers within 1–4 days after treatment. Therefore, these authors felt that repeat peeling at 2-week intervals would allow sufficient time for the skin to recover.