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

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

Chérie M. Ditre, Katherine D. Chilek

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.

• Histologic effects

It has been long held that lower concentrations of AHAs, when applied topically, reduce the thickness of the hyperkeratotic stratum corneum by reducing corneocyte cohesion in the lower levels of the stratum corneum. When applied in higher concentrations and low pH values, these same AHAs can cause epidermolysis as they have been found to work at the desmosomal attachment sites of the basilar layer. This effect can then produce varying degrees of exfoliation of the skin and therefore AHAs are useful in the management of various cosmetic and dermatologic conditions such as dry skin, seborrheic dermatitis, callosities, acne (Fig. 16.1), scarring (Fig. 16.2) actinic and seborrheic keratoses, and warts as well as photodamaged skin.

Fig. 16.1 Acne treatment can be enhanced through use of glycolic acid peels. (A) Before. (B) After

Fig. 16.2 The appearance of acne scarred skin can be minimized with repeated alpha hydroxy acid peels (A) Before. (B) After

• 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).

Fig. 16.3 Whitening of the skin following application of an alpha hydroxy acid peeling solution indicates cellular adhesion disruption and the initiation of exfoliation. (A) Before. (B) After

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).

Fig. 16.4 Alpha hydroxy acid peels can be used on the chest to improve acne and skin texture. (A) Before. (B) After

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.

• Role in moisturization

Unlike salicylic acid, AHAs have the ability not only to cause exfoliation but also moisturization. This dual nature of AHAs has been noted but not completely understood. It is postulated that the AHAs induced increased mucopolysaccharide content, in particular dermal glycosaminoglycans (GAGs), in the skin, which may account for the increased moisturization. It was shown in one study that 20% GA treatment of forearm skin as compared to vehicle demonstrated an increase in hyaluronic acid content in the epidermis and dermis. An increase in collagen mRNA gene expression was found in the AHA-treated sites only.

There are relatively few data on the effects of AHA on stratum corneum lipids. In their unpublished data, Motta and Berardesca indicate that an increase in production of ceramides occurs with AHA use. This would provide one explanation for the moisturization and barrier fortification that these products deliver (Fig. 16.5).

Fig. 16.5 Improvement in skin texture following an alpha hydroxy acid peel is demonstrated. (A) Before. (B) After

• 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.

• Effects on UVB-induced skin tumors

GA may exert inhibitory effects on UVB-induced skin tumor development by blocking UVB-induced apoptosis through inhibition of c-fos expression and activation of activator protein-1 (AP-1). This effect may also be due to inhibition of p53–p21 response pathways. GA was applied twice daily after UV irradiation given 5 days per week to hairless mice. Transcription factors AP-1 and nuclear factor kappa B (NF-κB) activation was significantly lower in UV- and GA-treated skin compared with activation in UV-irradiated skin alone. There was also decreased expression of UV-induced cell cycle regulatory proteins, proliferating cell nuclear antigen (Ag) (PCNA), cyclin D1, cyclin E, and the associated subunits cyclin-dependent kinase 2 (cdk2) and cdk4. The expression of signal mediators p38 kinase, jun N-terminal kinase (jnk) and mitogen-activated protein kinase (MEK) was lower in GA-treated skin compared with expression in UV-treated skin alone. Therefore, GA reduced tumor development. This protective effect of GA was quantitated to be a 20% reduction in skin tumor incidence, a 55% reduction of tumor multiplicity (number of tumors/mouse), and a 47% decrease in number of large tumors (>2 mm). GA was tested for maternal and developmental toxicity in pregnant rats and their pups when the pregnant rat was given GA in water over gestational days 7 through 21. At doses of 150 mg/kg there was no observed effect level (NOEL) in maternal or developmental toxicity. However, there were reported levels at doses four times higher than this.

• Photosensitivity

In 2003, the backs of 29 Caucasians were treated daily with 10% GA (pH 3.5) and compared to placebo in a randomized double-blind study over 4 weeks and then subjected to treatment with UV light at 1.5 MED. GA caused enhanced sensitivity to UV light as measured by sunburn cell induction and lowered MEDs. This effect abated after 1 week of the GA treatment. The conclusion of the authors was that short-term (1 month) application causes photosensitivity. In other unpublished data, AHAs may increase the need for sunscreen to a level equivalent of surfactant use, i.e. washing the skin with soap and water, namely SPF 2, to adequately protect from photosensitivity. There are no published data about the long-term use of GA and photosensitivity. However, since 2000, the FDA has been undertaking an AHA photocarcinogenicity study and is working with the National Toxicology Program to continue to study AHA safety.

• Effects on pigmentation

Interestingly, in that same year an in vitro study showed that GA and LA in doses of 300 or 500 μg/mL suppressed melanin formation by directly inhibiting tyrosinase activity. Adjusting the pH up to 5.6 did not affect tyrosinase activity and this effect was then deemed independent of the acidic nature of these AHAs. The authors postulate that GA and/or LA might work on pigmented lesions by accelerating epidermal turnover and by directly inhibiting melanin formation in melanocytes. There have been conflicting clinical studies showing no benefit to a positive benefit in patients with hyperpigmented skin conditions. It is our belief that the AHAs may actually work clinically by enhancing penetration of other bleaching agents such as hydroquinones or retinoids and/or by directly inducing skin turnover which improves the appearance of hyperpigmentation due to hyperkeratinization (Fig. 16.6).

Fig. 16.6 Alpha hydroxy acids can be used to improve the skin texture and color of persons with deeply pigmented skin. (A) Before. (B) After

• Cosmeceutical effects

In 1996, topical 8% GA and LA creams were compared in a double-blind, vehicle-controlled, randomized clinical trial of the effects on photodamaged skin of 74 women aged 40–70 years over 22 weeks. The study showed that AHA creams were well tolerated and found to be modestly beneficial in ameliorating the clinical signs of photodamage. After 10 weeks of treatment, both GA and LA significantly reduced mottled hyperpigmentation of the forearms compared with the vehicle. This effect was maximized by 14 weeks of treatment. At the end of this study, only LA showed a continued significant advantage over the vehicle. AHA induced significant reductions in skin sallowness as observed at 10 weeks, maximized at 14 weeks and maintained throughout the 22 weeks of the study over vehicle. There was a 16% greater diminution of tactile roughness with AHAs as compared to vehicle alone. Only the subjects using AHAs noted improvement from baseline in number of fine wrinkles, firmness, age spots or evenness of color.

In our study in that same year, it was shown that AHAs (GA, LA, and CA) all produced an improvement in photoaging markers. Histologically, it was shown that AHAs in a 25% concentration could cause epidermal and papillary dermal thickening, yield a more undulating rete ridge pattern, increase acid mucopolysaccharides, improve the quality of the elastic fibers, and increase the collagen density.

• Combination with other antiaging agents

Another study described the use of 15% GA versus 0.1% estradiol versus the combination of GA/estradiol on postmenopausal women. Sixty-five patients were treated with one agent alone or in combination to one side of the face, and the vehicle to the opposite side, for 6 months. This study showed that epidermal thickness increased by 23% with estradiol, 27% with glycolic acid, and 38% with the combination.

Kligman et al looked at the compatibility of AHAs with retinoids. They reported that in 20 adolescents with moderate acne vulgaris the use of AHAs with either 0.025% or 0.05% tretinoin was tolerated and that there were only mild adverse subjective reactions which occurred in both placebo- versus AHA-treated skin sites. In the photoaged group, 20 women aged 39–60 years were given tretinoin 0.05% for the first 2 months, which was then increased to 0.1% for the remaining 4 months. GA 8% was applied to the entire face. The manifestations of stinging, dryness, itching, and occasional mild peeling and erythema were noted in the first 6 weeks and then lessened. There were no more complaints than usually encountered with tretinoin alone. At the end of the study, 50% of the patients had moderate effacement of wrinkles. Two-thirds of the patients felt that their skin had less dry scaling and that the skin’s surface was definitely smoother. It was felt that the combination of AHA and retinoids caused no more difficulty than the use of tretinoin alone. It is postulated that there is a synergistic effect with the two agents.

SALICYLIC ACID

Salicylic acid is a phenolic aromatic acid, 2-hydroxy-benzoic acid or o-hydroxy benzoic acid. It has been popularized as a beta hydroxy acid but this description has been refuted chemically since the hydroxyl and carboxyl groups are directly attached to an aromatic benzene ring. These groups can then exhibit an acidic property like its analog, phenol. In AHAs, BHAs such as tropic acid, and PHAs, the hydroxyl and carboxyl groups are attached to an aliphatic or alicyclic carbon chain and the hydroxyl group is neutral in chemical property.

Salicylic acid is used in cosmetic formulations as a denaturant, hair-conditioning agent, and skin-conditioning agent, and is available in a wide range of cosmetic products at concentrations ranging from 0.0008 to 3%. SA is fat soluble and this property makes it useful in patients with oily skin.

• Mechanism of action

It has also been contested that the mechanism of action of SA at concentrations from 2 to 12% is simply due to keratolysis of the stratum corneum without effect on deeper skin components. This draws the contrast between the AHAs, which have been touted to modulate keratinization at the lower levels of the stratum corneum adjacent to the stratum granulosum (see above). However, there are some data to suggest that SA works on the intercellular spaces between corneocytes in the stratum corneum.

One recent study indicates that SA acts at the level of transcription to downregulate the production of fibrinogen, fibronectin, and alpha-hemolysin virulence factors necessary for bacterial replication in host tissues. Whether SA affects bacterial production in acne has not been reported here.

• Toxicity

Salicylates are absorbed percutaneously and approximately 10% of applied salicylates can remain in the skin. This has created a controversy over the risk of salicylism due to SA application over a large surface or compromised skin over a sustained period of time. Salicylism has been shown to occur with methyl salicylate ointments and high concentrations of SA on widespread areas of hyperkeratotic skin but there are no known cases resulting from SA acne products. Therefore, it is best to be cautious when using SA in childhood, pregnancy, lactation, and concomitant drug therapy, simply because relevant drug studies are lacking. Nonetheless, an exposure assessment of a representative cosmetic salicylate product used on a daily basis estimated that the exposure would be only 20% of the level seen with ingestion of a ‘baby’ aspirin (81 mg) on a daily basis. Little acute toxicity (LD₅₀ in rats; >2 g/kg) via a dermal exposure route is seen for SA. Subchronic dermal exposures to undiluted methyl salicylate were associated with kidney damage. Methyl salicylate is used as a denaturant and flavoring agent (0.0001–0.6%).

Hairless Skh:hr1 mice were irradiated with UVB light for 14 weeks and were then subjected (with or without treatment) every 2 weeks to 30% salicylic acid in polyethylene glycol (PEG) for a total of 18 weeks. In this study, it was interesting to note that the total number of skin tumors was greatly reduced in the treated versus the control mice. Skin tumor development was also slower in the treated versus the control mice. Fractions of T and B lymphocytes and natural killer cells from spleens of both groups of mice were comparable, and interferon-gamma production did not differ. It was then suggested by the authors that chemical peeling with salicylic acid in PEG may help to prevent as well as to reduce the number of UVB-induced skin tumors.

• Safety

Because of the possible use of these ingredients as well as the AHAs as exfoliating agents, a concern exists that repeated use may effectively increase exposure of the dermis and epidermis to UV radiation. It was concluded by the Cosmetic Ingredient Review Expert Panel that the risk of increased UV radiation damage with the use of any exfoliant, including salicylic acid and salicylates, necessitated the cosmetic industry taking steps to formulate ingredients that are nonirritating with these exfoliating agents so as not to increase sun sensitivity, or to include directions for the daily use of sun protection. Available data were not sufficient to establish a limit on concentration of these ingredients, or to identify the minimum pH of formulations containing these ingredients, such that no skin irritation would occur. With the information that is presently available, the Cosmetic Ingredient Review Expert Panel reached the conclusion that when formulated in this way these ingredients are safe. It is interesting to note that ethylhexyl salicylate (formerly known as octyl salicylate) is used as a fragrance ingredient, sunscreen agent, and UV light absorber (0.001–8%).

• Combining with other agents

Salicylic acid is reported to enhance percutaneous penetration of some agents (e.g. vitamin A), but not others (e.g. hydrocortisone). Its use as an antiaging agent has also been debated. It is anecdotally reported to be superiorly tolerated in rosacea skin types compared with GA. Clearly, it is useful because of its effect on oily skin types with acne vulgaris.

• Salicylic acid derivative

A C₈ derivative of SA known as beta-lipohydroxy acid (LHA), developed by L’Oréal Recherche in the late 1980s, has been proposed as an exfoliant and as a treatment of photoaged skin and acne.

While SA has a benzene ring structure, LHA has an eight-carbon acyl fatty chain linked to the fifth carbon of the benzene ring, making it more lipophilic than SA. This may account for its different properties, including a slower skin penetration. Studies have revealed that SA and LA appear to act uniformly into the overall thickness of the stratum corneum, while LHA seems to limit its action to the superior third of the stratum corneum, acting on the whole structure of the corneodesmosome. Examination of detached skin fragments has shown that treatment with topical LHA is more likely to result in shedding of isolated intact corneodesmosomes when compared to SA.

In isolated human skin, Piérard et al found that 0.025% retinoic acid (RA) and 1.5% LHA revealed significant increases in the thickness of the viable epidermis and its renewal rate when compared to 5% SA. Another study established that 2% LHA mimicked some effects of 0.05% all-trans retinoic acid on aging skin. While LHA was less effective than RA in correcting atypia and atrophy of the epidermis, it was more effective than 10% glycolic acid lotion, which in their study showed no beneficial effect. The pH of the lotion was not discussed, however. LHA was also shown to have a good safety profile, with lower irritation when compared to RA or GA.

Nonetheless, there are some new uses of RA in an exfoliating masque by Topix Pharmaceuticals that demonstrate efficacy in acneiform and photoaging skin. Dose-dependent studies are presently underway, and safety in pregnancy and nursing are still cautioned.

Both RA and LHA show comparable activity in decreasing melanosome cluster frequency and epidermal pigmentation. Furthermore, while AHAs appear to increase skin sensitivity to UV radiation, following the daily application of LHA, the skin’s resistance to UV-induced damage was increased.

RA has known comedolytic and anticomedogenic activity, while AHAs are of limited help in treating acne. However, the lipophilic nature of LHA gives it an affinity for sebum-blocked pores. Daily application of 2% LHA to the face was found to decrease the number of follicular casts by 47% (P <0.01) when compared to untreated skin. LHA has also been found to have antibacterial effects, which are ideal for the treatment of acne.

In addition to these antibacterial effects, in vitro experiments have shown that LHA has an antifungal activity against Malassezia ovalis similar to that of piroctone olamine (Octopirox), an ingredient found in antidandruff compounds.

In terms of cosmetic benefit, two separate studies demonstrated that patients using emulsions containing 1% LHA over several months found improvement in skin smoothness, suppleness, hydration, firmness, hue, and glow.

POLYHYDROXY ACIDS (PHAs)

• Definition

A new generation of AHAs, called polyhydroxy acids (PHAs), was found to provide similar effects as AHAs but do not cause the same sensory irritation responses. The prototype of these cosmeceutical agents of PHAs are gluconolactone and lactobionic acid. Gluconolactone is part of the energy-producing pentose phosphate shunt pathway in cells and is found in many medicinal products as the ligand with metals (e.g. with iron to produce ferrous gluconate). Gluconolactone is considered to be an alpha, beta, gamma, delta and epsilon AHA as there are five hydroxyl groups on this molecule and hence the term polyhydroxy acid.

PHAs provide additional humectant and moisturization properties compared with AHAs and can enhance stratum corneum barrier function, therefore increasing the skin’s resistance to chemical challenge. Most PHAs also possess antioxidant properties.

PHAs have been found to be compatible with clinically sensitive skin, including rosacea and atopic dermatitis, and can be used after cosmetic procedures. PHAs such as gluconolactone or lactobionic acid may be used in combination with other products, ingredients, or procedures such as laser and microdermabrasion to provide additional benefits to therapy or to enhance the therapeutic effect.

• Photosensitivity

Because gluconolactone is capable of chelating metals, it may function by scavenging for free radicals and thus protect the skin from photodamage. In a transgenic mouse model, gluconolactone provided up to 50% protection against UV radiation. The postulate here is that gluconolactone protects against UV radiation by inducing elastin promoter activation.

• Combining with other agents

PHA-containing products were used in combination with retinoic acid in treating adult facial acne and were found to be well tolerated. PHAs plus retinyl acetate (provitamin A) in a cream base exhibited significant antiaging skin benefits such as skin smoothing and plumping. PHAs plus hydroquinone showed excellent improvement in antiaging and skin lightening parameters. Finally, PHA-containing products were shown to be compatible with African–American, Caucasian, and Hispanic/Asian skin and provided significant improvements in photoaging in these populations.

• Comparison between AHAs and PHAs

A 12-week clinical study evaluated gluconolactone-containing products (PHAs) in comparison with glycolic acid-containing products (AHAs). Clinical grading of photoaging on 30 Caucasian women, as well as objective and subjective irritation, was conducted on the face at baseline and after 6 and 12 weeks of product use. Pinch recoil, silicone replicas of the crow’s-feet area, and self-assessment of product efficacy and tolerance were also collected. Both regimens showed significant antiaging benefits to skin. There were only two statistically significant (P <0.05) differences between the regimens in antiaging benefits: (1) sallowness showed greater improvement with AHA use at week 12 only (AHA, 17.1%; PHA, 12.4%), and (2) pinch recoil showed greater improvement with AHA use at week 12 only (AHA, 13.5%; PHA, 10.2%). However, the PHA regimen was better tolerated than the AHA regimen. Stinging and burning were significantly worse for subjects in the AHA treatment group at both week 6 and week 12.

CONCLUSION

Larger cohort studies need to be done to fully evaluate the efficacy as well as the mechanism of action of PHAs as well as the AHAs and BHAs (SA). The safety and toxicity of these agents are thought to be well controlled when formulated in a nonirritating vehicle and when combined with sunscreen. It is our belief that these agents do indeed increase the efficacy of other combined agents and that with further studies this will be more clearly understood.

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

INTRODUCTION

ALPHA HYDROXY ACIDS (AHAs)

• Definition

• Histologic effects

• Mechanism of action

• Role in moisturization

• Their role in skin barrier function

• Effects on UVB-induced skin tumors

• Photosensitivity

• Effects on pigmentation

• Cosmeceutical effects

• Combination with other antiaging agents

SALICYLIC ACID

• Mechanism of action

• Toxicity

• Safety

• Combining with other agents

• Salicylic acid derivative

POLYHYDROXY ACIDS (PHAs)

• Definition

• Photosensitivity

• Combining with other agents

• Comparison between AHAs and PHAs

CONCLUSION

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