Antiaging Benefit Ingredients: AHAs, PHAs, and Bionic Acids

AHA structure

AHAs are among the most widely studied and commonly used ingredients in cosmetic skin care products. The simplest of the hydroxy acid compounds, these organic carboxylic acids feature one hydroxyl group attached to the alpha position of the carboxyl group. The hydroxyl and carboxyl groups are both directly attached to an aliphatic or alicyclic carbon atom rendering the hydroxyl group chemically neutral, and only the carboxyl group provides an acidic property. Many AHAs are naturally present in foods and fruits.

Glycolic acid, the smallest (MW 76) and the most commonly used AHA, is found in sugar cane. Lactic acid, found naturally in tomatoes, is another small AHA molecule (MW 90) that is widely used in topical formulations to exfoliate and provide antiaging benefits. Ubiquitous in nature as an intermediate in the Krebs cycle and found naturally in many citrus fruits (at a concentration of 5% to 9%), citric acid is both an alpha- and a beta-hydroxy acid. It possesses a single hydroxyl moiety that is located in a position that is both alpha and beta relative to the acidic carboxyl group. Aside from its various industrial and food uses, citric acid has profound effects on skin morphology, delivering significant antiaging benefits including reduction in melanin for pigment evening ( Fig. 13.1 ).

Some AHAs contain a phenyl group as a side-chain substituent changing the solubility profile of the AHA, providing increased lipophilicity. This property makes them well suited to target oily and acne-prone skin compared to conventional water-soluble AHAs. Mandelic acid (phenyl glycolic acid) and benzilic acid (diphenylglycolic acid) are examples of this class of AHAs.

Histological effects of AHAs

Drs Van Scott and Yu made a novel discovery when they demonstrated the benefits of AHAs on normalizing the process of skin keratinization in severe hyperkeratotic conditions such as lamellar ichthyosis. They published their pioneering findings in 1974, clearly demonstrating the clinical and histological effects of topically applied AHAs on skin desquamation. Their early research showed concentration dependent effects on skin; continuous application of low concentrations (i.e. 10% glycolic acid) caused a profound normalizing effect on ichthyotic skin. Conversely, short discontinuous applications of high concentrations at low pH (e.g. topical peel strength) provoked epidermolysis.

Further research by Van Scott and Yu revealed benefits beyond exfoliation, securing a significant role for these compounds in antiaging skin care. Topical application of AHAs at concentrations of 10–25% caused increased biosynthesis of dermal GAGs and collagen fibers and also improved the quality of photoaged elastic fibers. Additional screening work revealed that twice-daily application of AHA cream formulations (10–35%) to forearms for 1 to 9 months versus a control cream caused a measurable increase in skin thickness using calipers. Corresponding histological analysis revealed increased biosynthesis of GAGs and collagen fibers, which explained the significant increase in skin thickness that was observed. After these initial findings, decades of clinical, histological and cellular research have further supported the antiaging effects of glycolic acid and other AHAs on stratum corneum desquamation, epidermal proliferation, dermal matrix remodeling and melanin distribution; for example, a study by showed the effects of AHAs on photoaged human skin by both clinical and microanalytic methods. Glycolic, lactic, or citric acid containing lotion (25%) was applied to one forearm versus a placebo lotion which was applied to the contralateral forearm over a period of 6 months. Forearm thickness measurements were conducted throughout the study using digital micrometers and biopsy specimens were collected from both arms for end-point analysis. Results demonstrated a 25% increase in skin thickness in AHA-treated forearms which was significantly greater than the vehicle control arm. Specifically, epidermal and papillary dermal thickness increased with AHA treatment compared with vehicle ( P < 0.05); other dermal changes included increased acid mucopolysaccharides, improved quality of elastic fibers and increased density of collagen with no evidence of inflammation. A decrease in epidermal melanin clumping was also observed. This pivotal study clearly demonstrated the manifold antiaging effects of AHAs. Many other clinical studies have also demonstrated changes in dermal biosynthesis with corresponding changes in skin thickness following AHA use.

Clinical effects of cosmetic AHAs

Antiaging effects of cosmetic AHAs have been demonstrated in rigorous clinical studies that have been published in peer-reviewed journals. For example, in a randomized, double-blind, vehicle-controlled study conducted by , photodamaged skin of 74 women was treated for 22 weeks with topical glycolic acid or lactic acid creams (8%). The AHA cream was applied monadically to the face and in a paired comparison to one forearm, leaving the remaining forearm for the vehicle control. Results showed the AHA creams were well tolerated and significantly improved photodamaged skin. Both glycolic and lactic acid significantly reduced mottled hyperpigmentation and/or sallowness on the forearms in comparison to the vehicle control ( P < 0.05). Subject self-assessment supported the clinical-grading results findings noting improvements from baseline in reduction of fine lines, firmness of skin, reduction of age spots and evenness of pigmentation.

Another randomized, double-blind, vehicle-controlled face and neck study conducted by compared a 5% unneutralized formulation of glycolic acid to its vehicle control over a period of 12 weeks. Glycolic acid treatment showed significant improvement in physician-assessed skin texture and a trend toward overall improvement in discoloration versus vehicle control. The effects of topical glycolic acid creams (8%, pH 3.8) were assessed compared to vehicle control creams in several studies using the photodamaged arm model. Antiaging benefits following AHA use were found to be reproducible. Notably, glycolic acid provided significantly greater improvement to crepe-like skin appearance than its vehicle control after 8 and 12 weeks of use. A split-face study by compared 8% glycolic acid cream (pH 3.8) to vehicle and incorporated objective instrumental assessments including digital photography, ballistometry and 3D facial scanning. These instruments measured signs of photodamage including elasticity and firmness, and captured an overall 3D image of length and depth of fine lines and wrinkles. The measures provide a quantitative method to assess early changes in periorbital, glabellar and nasolabial target benefit areas. Fine lines and wrinkles were fewer and less deep in the periorbital area after 8 weeks of treatment with glycolic acid. Skin tone was also noticeably improved and the overall texture of the skin was smoother. AHAs have clearly demonstrated significant clinical benefits to photodamaged both qualitatively and quantitatively including improvements to skin tone, aged appearance, crepiness, discoloration, smoothness, and fine lines and wrinkles.

Mechanism of action of AHAs

The exact mechanisms by which AHAs affect the skin are not completely understood. Insights into possible mechanisms can be based on available in vitro and clinical data. Early ultrastructural evaluations have revealed the following clues in determining potential mechanisms of action, including diminished corneocyte cohesion at the lower level of the stratum corneum; diminished number and strength of desmosomal attachments between adjacent corneocytes; increased epidermal and dermal skin thickness in photoaged skin, which may correspond with in vitro observations of increased keratinocyte and fibroblast proliferation ( , ), as well as increased dermal synthesis of GAGs and collagen fibers.

Recent research has focused on other mechanistic approaches to the possible role of AHAs in benefiting aged skin. For example, several in vitro studies have looked at the effects of AHAs on fibroblast cells to better understand the dermal remodeling action of AHAs observed in vivo. Human dermal fibroblast cells exposed to glycolic or l -lactic acid in cell culture produced significantly higher levels of procollagen I in a dose-dependent manner ( ). Similar effects were seen in two other studies which utilized ³ H-proline labeling as a quantitative measure, suggesting that AHAs have a stimulatory effect on collagen at the level of protein synthesis ( , ).

AHAs may also influence epidermal-dermal cellular communication. investigated the effect of glycolic acid on dermal matrix metabolism in both in vitro and ex vivo systems. They found a direct, dose-dependent increase in collagen synthesis following glycolic acid treatment in fibroblast cells. Keratinocytes treated with glycolic acid released higher levels of the interleukin IL-1α and this effect was also observed ex vivo. Interestingly, when fibroblasts were exposed to conditioned medium from keratinocytes treated with glycolic acid, an upregulation of matrix metalloproteinases MMP-1 and MMP-3 mRNA expression levels was seen. The effect on MMP levels was most likely mediated by IL-1α, which was upregulated by glycolic acid in keratinocytes.

Topical uses of AHAs

Descaling effect

AHAs have long been shown to influence hyperkeratinization by modulating corneocyte attachment at the base of the stratum corneum, resulting in a specific desquamation effect unlike the nonspecific effect of traditional keratolytic agents. This effect is clearly visible on hyperkeratotic skin, such as lamellar ichthyosis, and was recently investigated for use on psoriatic plaques. Salicylic acid is the current descaling treatment of choice for psoriatic plaques. However, its use has been shown by Van Scott and Yu (2005) to cause dermal thinning which could exacerbate corticosteroid-induced atrophy, whereas AHAs increase dermal biosynthesis and have been shown to counteract corticosteroid-induced dermal thinning ( ). In a double-blind, active-controlled, bilateral comparison, a 20% AHA/PHA/bionic acid blend cosmetic cream formulated at pH 3.7 demonstrated a significantly greater descaling effect after 1 week of treatment in comparison to prescription-strength salicylic acid (6%, pH 4.4). Both products were applied twice daily and were equally well tolerated ( Fig. 13.2 ). HAs are effective descaling agents and may be preferred over salicylic acid to help counteract dermal thinning effects of topical corticosteroids.