Hydroquinone has been the gold standard for the treatment of hyperpigmentation for more than 50 years and is
believed to reduce the production of melanin by inhibiting the enzyme tyrosinase.2 In the United States and Canada, formulations of hydroquinone with a concentration of up to
2% can be sold over-the-counter without a prescription and formulations up to 4% are available with a prescription. Due to their higher concentration, the 4% prescription
formulations are more efficacious, and quicker to show their effects, than the over-the-counter formulations.2
There are multiple advantages of using L-ascorbic acid in conjunction with hydroquinone. First, it may
enhance the penetration, and hence efficacy, of hydroquinone.2 Second, as an antioxidant, L-ascorbic acid offers protection against free radicals produced after
exposure to ultraviolet light and can therefore help prevent the development of further photodamage.3-5 Third, L-ascorbic acid is essential for collagen
biosynthesis and reduces melanin synthesis by inhibiting tyrosinase-mechanisms of action which may help reduce fine lines and wrinkles, and dyspigmentation, respectively.
6,7
Vitamin C is an unstable molecule that readily oxidizes when exposed to light or air and must be formulated
appropriately to ensure adequate stability, bioavailability, and effectiveness-as factors such as the pH of its formulation can influence its efficacy.8-11 The
importance of appropriate formulation is demonstrated by the results of an in vitro study using human skin which showed greater L-ascorbic acid stability, and greater delivery
of bioavailable L-ascorbic acid to the viable layers of the skin, with an optimized formulation containing 10% L-ascorbic acid and 4% hydroquinone than with a leading
competitor formulation containing 20% L-ascorbic acid.11 A more than 10-fold greater absorption of L-ascorbic acid was evident with the optimized formulation
compared with the competitor product.11 (The optimized formulation in the Agahigian study is the clarifying serum used in the version of the hydroquinone/L-ascorbic
treatment system for individuals with normal to dry skin.)
In addition to 4% hydroquinone and 10% L-ascorbic acid, the treatment system used in the study presented here
also contains vitamin E, witch hazel, aloe barbadensis leaf juice, other penetration-enhancing ingredients, and sunscreens. Vitamin E is included as it is believed to act
synergistically with vitamin C,4-6,12 and witch hazel and aloe barbadensis leaf juice are both reported to possess anti-inflammatory activity.13-15 In
addition, witch hazel has been reported to have potential anti-aging effects, with potent scavenging activity against active oxygen16 and suppression of UV-induced
erythema.15 Ingredients included in the treatment system to enhance skin penetration include sodium lauryl sulfate, ethanol, and propylene glycol. And the two
sunscreens included are broad spectrum sunscreens-micronized zinc oxide (a physical sunscreen) and octinoxate (a
