A theory for the mechanism of action of the alpha-hydroxy acids applied to the skin

Med Hypotheses. 1999 Nov;53(5):380-2. doi: 10.1054/mehy.1998.0788.


A theory for the mechanism of action of alpha-hydroxy acids topically applied to the skin is proposed on the basis of an analysis with the experimental and clinical data. The alpha-hydroxy acids reduce the calcium ion concentration in the epidermis and remove calcium ions from the cell adhesions by chelation. This causes a loss of calcium ions from the cadherins of the desmosomes and adherens junctions, from the tight junctions, and possibly also from other divalent metallic cation-dependent cell adhesion molecules. The cell adhesions are thereby disrupted, resulting in desquamation. Desquamation is enhanced by cleavage of the endogenous stratum corneum chymotryptic enzyme on the cadherins, which are otherwise protected from proteolysis by conjugation with calcium ions. The decrease of calcium ion level so brought about in the epidermis also tends to promote cell growth and retard cell differentiation, giving rise to a younger-looking skin. This property of alpha-hydroxy acids suggests that caution should be taken with excessive and chronic use of these compounds and studies in this regard are warranted. Alpha-hydroxy acids may also possess anti-inflammatory capacities.

MeSH terms

  • Cations, Divalent
  • Cell Adhesion
  • Chelating Agents / pharmacology
  • Humans
  • Hydroxy Acids / pharmacology*
  • Skin / cytology
  • Skin / drug effects*


  • Cations, Divalent
  • Chelating Agents
  • Hydroxy Acids