AHA current data on safety, skin structure/physiology effects "not sufficient" -- FDA.

AHA DATA ON SAFETY, SKIN PHYSIOLOGY EFFECTS "NOT SUFFICIENT," FDA concluded in a Feb. 22 review of data on two alpha hydroxy acids -- glycolic acid and lactic acid -- and their common salts and simple esters. FDA noted that it analyzed the AHA data with two endpoints in mind: whether AHA products sold at retail for home use are safe for both short-term and repeated or long-term use, and to determine the effects of AHAs on the structure/physiology of the skin.

FDA concluded that "although some observations are possible, the data available to date are not sufficient to provide definitive answers to these questions." The agency contracted Silver Spring, MD-based KRA Corp. to perform the data review.

The analysis has been submitted to the Cosmetic Ingredient Review Expert Panel in anticipation of the group's upcoming review of glycolic acid and lactic acid at its March 4-5 meeting in Washington, DC. The FDA document is based on existing literature on the AHAs and the agency's information about consumer AHA adverse reactions ("The Rose Sheet" Nov. 13, p. 2).

CIR is scheduled to issue a tentative report on the safety of glycolic acid and lactic acid at the meeting. The group was previously slated to consider AHAs at its Dec. 12 meeting but agreed to postpone the review until FDA had completed its own analysis ("The Rose Sheet" Dec. 18, p. 5).

FDA's report does include some general observations about glycolic acid and lactic acid based on the data. The document addresses long-term adverse effects, effects on skin structure and physiology, effects on skin barrier function, short-term adverse effects and single treatment adverse effects. The document also details "areas of insufficient data" with recommendations for specific studies .

As to the effect of AHAs on skin structure and physiology, FDA surmised that a 70% glycolic acid chemical peel at pH 2 or below "obviously affects" the structure of the skin. "With lower concentrations at higher pH the answer is not so clear," the agency noted.

"The effects of AHAs on epidermal and dermal histology," however, "support the argument that AHAs alter skin structure under some conditions," FDA pointed out. Those effects include a decrease in the thickness of the stratum corneum, an increase in epidermal thickness, an increase of GAGs [glycosaminoglycans] in the dermis, and increased collagen deposition in the dermis, according to the FDA document.

The agency cited one study in particular that used 13% glycolic acid at a pH of 3.8: "The large changes in GAGs and collagen deposition after treatment...indicate that this treatment altered the structure of the dermis," FDA asserted. Elevated GAGs can indicate skin damage, according to FDA. With regard to skin barrier function, the document notes that "because AHAs may thin the stratum corneum, it is possible that they affect the barrier function of the skin." The report maintains that "concentration and pH will be important factors in determining the extent of any possible effects."

FDA's document concludes that the "possibility" that longer treatment periods with higher AHA concentrations "would lead to clinically relevant increases in TEWL [transepidermal water loss] cannot be ruled out from existing data." FDA recommended for example, a six-month study using 8% glycolic acid at pH 3.8.

Using AHAs at concentrations between 50-70% to peel the stratum corneum and segments of the epidermis "is certain to compromise barrier integrity," FDA added. In one study, nine 30-minute treatments with 30% lactic acid resulted in "significant degradation in barrier function" and TEWL increased to 30g/m2/hour, FDA said.

FDA additionally surmised that "the large decreases in MED [minimal erythema dose] after AHA treatment" found in another study "may also be related to thinning of the stratum corneum, thus weakening its barrier to UV radiation." In the 12-week study, 19 subjects were treated with 4% glycolic acid. Three of the subjects (15.8%) exhibited "large decreases in MED" after the AHA treatment, FDA said.

At CIR's Dec. 12 meeting, dermatologist Daniel Sauder, MD, University of Toronto testified that the reduction in MED found in a 12-week study of 19 subjects exposed to 4% glycolic acid "was not statistically significant" and was similar to the effect of a moisturizer or a sponge exfoliant. However, CIR panelist Arnold Schroeter, MD, Mayo Clinic, had expressed concern over the potential for AHA products to cause MED reduction in Type 1 (fair) skin, calling the risk "troublesome" ("The Rose Sheet" Dec. 18, p. 7).

With regard to long-term adverse AHA effects, FDA pointed out that there is "relatively little work published on long-term safety of 8% or higher products." The longest treatment duration in studies reported to date is six months.

The document notes that in the six-month studies, the products tested (6% concentration or lower, pH of 3.8 or above) "caused few measurable effects during this period of time." Although one 22-week study reviewed by the agency concluded that both 8% glycolic acid and lactic acid were safe, FDA notes that the pH of the products being tested was not provided.

Regarding short-term adverse AHA effects, the FDA report states that "cumulative irritation tests...show that AHAs have the potential to produce significant levels of skin irritation." Even nonoccluded patch conditions can result in "significant irritation" in cases of daily patch application, the document notes. Other short-term adverse effects include erythema, papules, dryness and "continual stinging," the analysis reports.

Single-treatment AHA adverse effects at concentrations ranging from 2%-20% included "transient stinging," erythema, papules, scaling, and flaking of the skin. At 50%-70% doses of lactic or glycolic acid, single treatments have been reported to have caused "severe stinging" and peeling of the epidermis. These dosages also "may cause scarring or hypopigmentation," the agency concluded.