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Volume 3 • Number 5 • May 1998
Contents: (Full text available in print edition.)
Current Review of the Alpha-hydroxy Acids

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

Few could have forecast the impact that the research on these compounds, initiated by Van Scott and Yu twenty years ago3, would have on the practice of dermatology and the product range promoted by the cosmetic industry. Since then, Van Scott and Yu, together with other investigators have:
  • Determined that AHAs are useful for dry skin and photodamaged skin.
  • Found that AHAs can be used by dermatologists in office procedures (e.g. chemical peels).
  • Contributed to development of a glucono-lactone formulation. This polyhydroxy AHA appears to be better tolerated by sensitive skin.
  • Played a watchdog role by commenting on unfounded performance claims made for a number of cosmetic products containing AHAs, and attempting to correct what they believe to be erroneous information and incorrect statements made in articles about AHAs.
Dr. Stuart Maddin, Editor

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

Adverse effects

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

AHAs Tretinoin
Category Cosmetics (non-drug category) Non-prescription Prescription drug approved by regulatory agencies in the US & Canada for the topical treatment of acne and photoaging
Action Modulate stratum corneum formation through diminished cellular cohesion between corneocytes. Affects keratcinocytes, melanocytes and collagen formation.
NOT useful The usefulness of AHAs for acne is awaiting further confirmation. For dry skin, rosacea or some disorders of keratinization.
USEFUL For dry skin, ichthyoses. Photoaging benefits are awaiting confirmation. For acne vulgaris, photoaging and hyperpigmentation.
Choice Depends upon therapeutic objectives, conbination use of both is often the most rational approach.5,6

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


  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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Update on Drugs
Class Name/Company Approval Dates and Comments
Anti-HIV Zidovudine 300 mg/
lamivudine 150 mg
Approved by the EC Commision. Combivir aims to improve compliance by reducing the pill burden for HIV patients on combination antiretroviral therapy.

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EDITOR: Stuart Maddin ASSOCIATE EDITOR: David I. McLean INTERNET EDITOR: Harvey Lui PRINCIPAL MEDICAL WRITER: Rodger Hall MEDICAL WRITER: Susan Kingsley MANUSCRIPT EDITOR: Rodger Hall  EDITORIAL ADVISORY BOARD: Kenneth A. Arndt, Beth Israel Hospital & Harvard Medical School, Boston; Wilma Fowler Bergfeld, Cleveland Clinic, Cleveland; Jan D. Bos, University of Amsterdam, Amsterdam; Enno Christophers, Universitäts-Hautklinik, Kiel; Hugo Degreef, Catholic University, Leuven; Richard L. Dobson, Medical University of South Carolina, Charleston; Boni E. Elewski, Case Western Reserve University, Cleveland; Barbara A. Gilchrest, Boston University School of Medicine, Boston; W. Andrew D. Griffiths, St. Johns Institute of Dermatology, London; Vincent C.Y. Ho, University of British Columbia, Vancouver; James J. Leyden, University of Pennsylvania, Philadelphia; Howard I. Maibach, University of California Hospital, San Francisco; Larry E. Millikan, Tulane University Medical Center, Louisiana; Takeji Nishikawa, Keio University School of Medicine, Tokyo; Constantin E. Orfanos, Freie Universitäts Berlin, Universitätsklinikum Benjamin Franklin, Berlin; Stephen L. Sacks, Viridae Clinic Sciences, Vancouver; Alan R. Shalita, SUNY Health Sciences Center, Brooklyn; Stephen K. Tyring, University of Texas Medical Branch, Galveston; John Voorhees, University of Michigan, Ann Arbor; Klaus Wolff, University of Vienna, Vienna
Skin Therapy Letter®. (ISSN 1201-5989) Copyright 1998 by International Skin Therapy Newsletter Inc. All rights reserved. Reproduction in whole or in part by any process in whole or in part is strictly forbidden without prior consent of the publisher in writing.
Published six times yearly by International Skin Therapy Newsletter Inc., 835 West Tenth Avenue, Vancouver, British Columbia, Canada V5Z 4E8. Tel: (604) 874-6112. Fax: (604) 873-9919. Annual subscription: Canadian $85 individual; $155 institutional (GST included). US $60 individual; $110 institutional. Outside North America: US$80 individual; $130 institutional. Quotes on multiple subscriptions and student rates supplied upon request.
Skin Therapy Letter Editor: Dr. Stuart Maddin Vol. 3 No. 5
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