• Current Review of the Alpha-hydroxy Acids
• FDA Warning about Isotretinoin (Accutane®, Roaccutane®)
• Update on Drugs
  • Diclofenac sodium – Solarase® Gel 3% – Hyal Pharmaceutical
  • Trovafloxacin (oral)/Alatrovafloxacin (IV) – Trovan® – Pfizer
  • Zidovudine 300 mg/lamivudine 150 mg – Combivir® – Glaxo Wellcome
  • Hydroquinone 4%, glycolic acid & antioxidant complex – Lustra® – Medicis Pharmaceutical
  • Leprosy vaccine
  • Minocycline – Minocin® – Lederle
  • Protease inhibitors

Alpha-hydroxy acids (AHAs) are naturally occurring organic carboxylic acids such as glycolic acid, a natural constituent of sugar cane juice and lactic acid, found in sour milk and tomato juice. Topical formulations incorporating these acids are now frequently used or prescribed by dermatologists and they are also present in a wide range of heavily promoted cosmetic products. The growth in sales of these products has been phenomenal. Back in 1994, sales of two products totalled $300 million dollars,¹ and by 1996 more than 45 companies were manufacturing over 200 different AHA-containing products.²

Mechanism of action

AHAs exfoliate dead skin cells and moisturize the skin.⁴ Their main action is to facilitate desmosomal degradation leading to an increase in corneocyte desquamation, an increase in cytokines and increased epidermal proliferation.⁵ There is also as an increase in hyaluronic acid (which holds 1000x times its weight in water)^5,6 and this might be one of the causes of increased skin 'plumpness'.⁶ By normalizing corneocyte cohesion, the stratum corneum is thinned and smoother and more flexible (even at low relative humidity⁷), and the formation of dry flaky scales is reduced.⁸ The overall result is skin which looks and feels better.⁸

Claims that AHAs reverse photodamage and reduce wrinkles, brown spots and roughness are somewhat controversial and are currently being reviewed by the Cosmetic, Toiletry and Fragrance Association (CTFA), the FDA and the Federal Trade Comission (FTC).⁴ Several aspects concerning the mechanism of action of AHAs are still unknown. In particular, little is known about the correlation between the histopathological and functional changes in the stratum corneum induced by AHA treatment.⁸ Studies have suggested that treatment with AHAs produce significant reversal of epidermal and dermal markers of photoaging.⁹

Therapeutic use

The end use is critical – is it to be used as a cosmeceutical, a dermatologic application or as a chemical peel?¹⁰

Formulation is more important than concentration alone.⁵ Bioavailability of the AHA is a major determinant; for example a high concentration of AHA near neutral pH is ineffective because the bioavailability is miniscule. At the other extreme, at low pH even small concentrations can be effective because a major amount of the AHA is available.⁶ The more free acid, the more biologic activity.⁵

An Expert panel of the US Cosmetic Ingredient Review (CIR) concluded in 1996:

• AHAs are safe in cosmetic products at concentrations of 10% or less, at a pH of 3.5 or greater, and formulated to avoid increasing the skin's sensitivity to the sun or accompanied by directions to use sun protection daily.
• Stronger formulations of AHAs (concentrations up to 30% and a pH as low as 3.0) are safe if applied by trained professionals. Such use should be brief, discontinuous, and followed by thorough rinsing and accompanied by directions to use sun protection daily.¹¹ Stronger concentrations are sometimes needed for the thickened stratum corneum seen in some dermatologic diseases.¹²

When formulations of AHAs are to be applied daily, chemical buffering or partial neutralization are important to ensure skin tolerance,^6,12,13 but to maintain the AHAs activity, buffering agents should not bring the pH above four.⁵ Formulations used for peeling purposes perform best when the AHA is completely bioavailable at its native low pH.⁶

AHAs are acids and can cause mild to moderate irritation unless they are neutralized in the final product. Low concentrations of AHAs appear to be less irritating than tretinoin, and no other adverse effects have been reported, but long-term studies have not been done.¹⁴ As is the case with tretinoin³, AHAs can sometimes cause stinging/burning in nasolabial and sub-orbital areas and local contact irritation.⁵ If an acid peel has been accomplished using glycolic acid, then photosensitivity is a concern for about two weeks after the peel.¹² In any case, sunscreen and sunblock agents should always be used to protect against solar damage.⁶

Future developments

Although glycolic and lactic acids are the two AHAs that we have had the most clinical experience with, other AHAs have properties which might make them suitable for specific uses.⁶

AHAs place in therapy

AHAs are the introduction of science to the cosmetic field, and for the first time in the cosmetic industry an ingredient is active and has profound beneficial physiologic effects.¹³ Previously, many claims made for cosmetics were based more on marketing than on science.¹²

With the AHAs, in deciding whether regulatory intervention or monitoring is necessary, the FDA and other agencies will examine the overall balance reached between use for scientifically justifiable indications, and misuse based on unproven, over-promoted claims.⁶

References

1. Hwan JS. Acid based wrinkle creams: fountain of youth or snake oil? Wall Street Journal April 13,1994.
2. Perricone NV, DiNardo JC. Photoprotective and anti-inflammatory effects of topical glycolic acid. Dermatol Surg 1996; 22: 435-437.
3. Van Scott EJ, Yu RJ. Control of keratinization with alpha hydroxy acids and related compounds. 1. Topical treatment of ichthyotic disorders. Arch Dermatol 1974; 100: 586-590.
4. Bergfeld WF. Cosmetic use of alpha-hydroxy acids. Cleveland Clin J Med 1997; 64: 327-329.
5. Leyden JL. Personal communication, August, 1997.
6. Van Scott EJ. Personal communication, August 1997.
7. Takahashi M, Machida Y. The influence of hydroxyacids on the rheological properties of the stratum corneum. J Soc Cosmet Chem 1985; 36: 77-78.
8. Berardesca E, Distante F, Vignoli GP et al. Alpha hydroxyacids modulate stratum corneum barrier function. Brit J Dermatol 1997; 137: 934-938.
9. Ditre CM, Griffin TD, Murphy GF et al. Effects of (a-hydroxy acids on photoaged skin: A pilot clinical, histologic, and ultrastructural study. J Am Acad Dermatol 1996;34: 187-195.
10. Maddin WS, Editor.
11. Bergfeld WF, Belsito DV et al. Final report on glycolic acid and lactic acid. Cosmetic Ingredient Review (CIR), 1101 17th St. NW, Suite 310, Wahington, DC 20036.
12. Perricone NV. Personal communication, August 1997.
13. Bergfeld WF. Personal communication, July 1997.
14. Topical drugs for aging skin. Med Letter 1997; 39: 78-79.

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