j. Cosmet. Sci., 52, 199-210 (July/August 2001) A double-blind evaluation of the activity of an anti-cellulite product containino retinol, caffeine, and ruscooenine by a combination of several non-invasive methods CHRISTIANE BERTIN, HELENE ZUNINO, JEAN-CHRISTOPHE PITTET, PATRICK BEAU, PASCAL PINEAU, MARC MASSONNEAU, CAROLINE ROBERT, and JOHN HOPKINS, Johnson &Johnson Consumer France, 1 rue Camille Desmoulins, 92787 Issy /es Moulineaux (C.B., H.Z., C.R., J.H.), Spincontrol, 7 rue Dabilly, 37000 Tours (J.-C.P., P.B.), and I•DP, 36 rue du Chemin Vert, 75011 Paris (P. P., M.M.), France. Accepted for publication April 15, 2001. Synopsis A double-blind, randomized, placebo-controlled study was conducted with 46 healthy female volunteers in order to test an anti-cellulite product containing retinol, caffeine and ruscogenine. An evaluation of different parameters related to cellulite appearance, i.e., the skin macrorelief, the dermal and hypodermal structures, the skin mechanical characteristics, and the cutaneous flowmerry was assessed using several non-invasive methods. This combination of different evaluation methods resulted in the demonstration of significant activity of the anti-cellulite product versus baseline and showed its superiority versus the placebo in skin macrorelief (decrease of the "orange peel" effect) and an increase in cutaneous microcirculation. By using a combination of methods, it was possible to detail the activity of an anti-cellulite product and to show superiority of the product in comparison with the placebo. INTRODUCTION Even though the subject of cellulite has received only minimal attention from the medical and scientific communities, it is nevertheless a real skin condition from which a high proportion of the female population actually suffers (1). This skin condition is associated with dimpling of the skin, or so-called "orange-peel" skin on the thighs and buttocks, and results from modifications of fat and fibrous tissue underlying the skin. Although the sequence of events leading to the appearance of cellulite is still debated, the cellulite-prone appearance results from the combination of fat 1obule enlargement with reactive focal fibrosclerotic hyperplasia of connective tissue strands, composed primarily of collagen and elastin fibers, partitioning the subcutaneous tissue. 199

200 JOURNAL OF COSMETIC SCIENCE Lymphatic and venous circulation in the tissue are impaired, and exchanges between the blood, the lymph, and the tissues are decreased (2,3). This may contribute to the damage of the fibroelastic strands. A vicious cycle ensues, in which enlarged fat 1obules increase the hypodermal pressure, further damaging the vessels and degrading the fibers (colla- gen and elastin fibers). Fat lobules are squeezed upward upon pinching the skin, while their belt of fibrosclerotic strands acts like shrouds bound to the deepest fascia (4). The skin on the thigh in women is easily deformed because the dermis is thin and the collagen bundles and the elastic network are vertically oriented, leading to the "orange peel" effect when the fibers are damaged. As the condition worsens, the dimpled aspect of the skin occurs spontaneously, without even pinching the skin. This study evaluated the effect of the association of three active ingredients present in a cosmetic product: caffeine, ruscogenine extract, and retinol. The evaluation of the test product was performed using an original combination of objective methods, which had not yet been used: ß Profilometric analysis of the skin's macrorelief of the external face of the thighs performed on digital images of pinched thighs ß 3D ultrasound imaging (evaluation of the dermal and hypodermal structures) ß Cutometry (evaluation of the mechanical properties of the skin of the thighs) ß Laser Doppler flowmerry (evaluation of the cutaneous microcirculation) MATERIAL AND METHODS PANELISTS Forty-six (46) healthy female volunteers, minimum 18 years of age, with normal skin were selected. They presented with a moderate level of cellulite in the thighs, and their weight/height ratio [body mass index (BMI) = weight/height] was between 20 and 25. All volunteers gave their informed written consent before beginning the test. STUDY DESIGN The format was a randomized, double-blind, placebo-controlled study. The study lasted three months (from the beginning of March until the end of May, 1999), the products were applied twice a day for three months (one thigh treated with the product and the other with the placebo). Measurements were taken before the first application, and then after 28 days, 56 days, and 84 days of application. PRODUCTS The complete product contained retinol, caffeine, ruscogenine extract, and alcohol. The placebo did not contain retinol, caffeine and ruscogenine extract (the alcohol was main- tained to give the same cosmetic perception on application). APPLICATION OF PRODUCTS The volunteers applied both products regularly and uniformly over the entire thigh by circular massage. Products were applied twice daily, under in-use conditions.