Tolerance Profile of Retinol, Retinaldehyde and Retinoic Acid under Maximized and Long-Term Clinical Conditions

Abstract

Background: Topical retinoic acid (RA) causes irritation of the skin. To prevent this side effect, natural precursors of RA have been proposed. The aim of the present study was to compare the local tolerance profiles of retinol (ROL), retinaldehyde (RAL) and RA. Methods: ROL, RAL and RA were studied using repeated insult patch tests for 14 days (n = 6). Similarly, RAL and RA were assessed in long-term clinical use for 44 weeks (n = 355). Clinical scoring on irritation, measurement of transepidermal water loss (barrier function) and laser Doppler blood flow perfusion units (irritation) were performed. Results: Under maximized conditions, an equally low irritation potential for ROL and RAL and a more pronounced irritant effect with RA could be demonstrated clinically (p < 0.05 in the intergroup analysis). Furthermore, RAL and RA induced more scaling than ROL (p < 0.05), and ROL and RA tended to induce more burning/pruritus than RAL (nonsignificant). The TEWL values were low with ROL and high with RAL and RA (nonsignificant, intergroup analysis). The laser Doppler measurements confirmed pro-irritating effects of RA and the nonirritating effects of ROL and RAL (p = 0.001, intergroup analysis). The long-term clinical study showed that the study population developed a high frequency of erythema (44% of the population), scaling (35%) and burning/pruritus (29%) with RA in the first 4 weeks of treatment, whereas these 3 parameters were significantly less frequent with RAL (p < 0.0001 in the intergroup analysis). Conclusion: The natural retinoids ROL and RAL do have a good tolerance profile, in contrast with the irritating potential of RA.

Favre-Racouchot Syndrome

“…Topical application of tretinoin or retinaldehyde alone or in conjunction with above procedures or oral isotretinoin (0.05-0.1 mg/kg) for 4-6 months is beneficial in some patients [1,7]. Retinaldehyde is less irritating than retinoic acid, significantly increases the surface area of elastic and collagen fibers, and reduces the appearance of the sun-damaged skin [7,8]. Sun protection will benefit in preventing progression.…”

In Vitro Assessment of the Tolerance Profile, the Metabolism and the Potential Depigmenting Activity of New Retinoid Derivatives

“…Topical RA induces a skin irritation that may lead to cessation of treatment. Topical RAL is quite less irritant and may be used for longer periods of time [30][31][32][33]. In this context it is interesting to have at one's disposal a new family of branched retinoids with a potential depigmenting effect, which could be added, alone or in combination, in skin lightening formulations.…”

Differentiation Therapy in Thyroid Carcinoma

“…Although retinol, compared to RA, shows a lower rate of adverse effects (e.g. Fluhr et al, 1999), the different intracellular concentrations of the active metabolite due to variations in serum retinol binding protein, in cellular transport proteins and in the activity of intracellular dehydrogenases diminishes its suitability as drug candidate in the treatment of TC.…”