The mechanism of action and application of retinoids in cosmetic products


7/27/20223 min read

How do retinoids work?

Retinoids are poorly soluble in body fluids, and specialized proteins are required for their transport into cells. There are several specialized proteins: some can bind retinol, while others bind retinoic acid, and so on. For example, retinol-binding protein (RBP) and cytosolic retinol-binding protein (CRBP) bind retinol but are localized in different cellular compartments. When retinol enters the cell's cytoplasm through these specialized proteins, enzymes are involved in the mechanism of action. The conversion of retinol into its active form, retinoic acid, through an enzymatic reaction known as oxidation. Upon entering the cell, the enzyme retinol dehydrogenase (RDH) or alcohol dehydrogenase (ADH) converts retinol into retinal. This reaction can be reversible, meaning that our body has an additional mechanism that regulates the local concentration of retinol in tissues. Later, the retinal is oxidized into retinoic acid, and this process is catalyzed by another enzyme called retinaldehyde dehydrogenase (RALDH), which is irreversible. The resulting retinoic acid can bind to nuclear receptors in cells, thus exerting its biological effects on specific tissues, organs, and cells [1-5].

Application of retinoids in cosmetology

Vitamin A and its derivatives, especially retinol, are among the most effective substances in slowing aging. Retinol, which is fat-soluble, penetrates the stratum corneum, and a minor concentration reaches the dermis. Once it becomes a keratinocyte, retinol penetrates its interior and performs its biological function through the abovementioned mechanism. The biological function of retinoids may vary. Some retinoids may influence transcription and the secretion of growth factors, contributing to epidermal cell proliferation (renewal), strengthening the protective function of the epidermis, and reducing excessive transepidermal water loss. On the other hand, other retinoids protect against collagen breakdown, inhibit the activity of metalloproteinases, and strengthen angiogenesis in the papillary dermis. In summary, most retinoids promote protein synthesis in the epidermis, accelerate the keratinization process, and have an anti-comedogenic effect, resulting in beautiful skin, reduced pigmentation spots, fine wrinkles, and acne scars.

So, which retinoids are most commonly used in cosmetology, and what effects do they have?

Tretinoin (retinoic acid) is the biologically most active form among retinoids, which increases the metabolism of epidermal cells and also causes the dispersion of melanin granules (resulting in a reduction of skin hyperpigmentation). The most commonly used concentration of tretinoin for addressing acne-prone skin issues ranges from 0.01% to 0.4%. Retinoic acid can have different formulations: gel (0.01%, 0.25%), cream (0.025%, 0.05%, 0.1%), microspheres (0.04%, 0.1%), solution (0.05%), and emollient (0.05%) [6, 7].

Retinol is the most commonly used retinoid in cosmetic products. It exhibits milder and better effects than retinoic acid (which is approximately 20 times stronger than retinol) and is effective in addressing skin hyperpigmentation, dryness, and fine wrinkles. Within the cell, retinol is converted into retinoic acid through a two-step oxidation process – first transformed into retinaldehyde, which is later oxidized into retinoic acid by specific enzymes. The concentration of retinol in cosmetic products typically ranges from 0.0015% to 0.3% [8].

Retinal is the aldehyde form of vitamin A, i.e., an oxidized form of retinol. The effectiveness of retinal in addressing various skin issues is limited. Like retinyl esters (retinyl acetate and palmitate), it is a stable vitamin A derivative but only slightly improves skin texture. Compared to retinoic acid, it is less irritating and well-tolerated [9]. Retinal and retinyl esters are highly stable, but they must first be converted to retinol and later to retinoic acid. Because of this, the impact of these retinoids on the skin is reduced.

Therefore, retinol and its active metabolites can effectively penetrate the skin's stratum corneum and perform a specific function. Depending on the type of retinoid present in the composition of a cosmetic product, such a product is suitable for addressing different skin issues and exhibits varying efficacy. For this reason, when choosing a cosmetic product, it is worth paying attention to the concentration of the retinoid and its type.

-- The LAB

  1. Duester G. Retinoic acid synthesis and signalling during early organogenesis. Cell. 2008;134:921–31.

  2. Zizola CF, Frey SK, Jitngarmkusol S, et al. Cellular retinol-binding protein type I (CRBP-I) regulates adipogenesis. Mol Cell Biol. 2010;30:3412–20.

  3. Varani J, Warner RL, Gharaee-Kermani M, et al. Vitamin A antagonizes decreased cell growth and elevated collagen-degrading matrix metalloproteinases and stimulates collagen accumulation in naturally aged human skin. J Invest Dermatol. 2000;114:480–6.

  1. Hyung SJ, Deroo S, Robinson CV. Retinol and retinol-binding protein stabilize transthyretin via formation of retinol transport complex. ACS Chem Biol. 2010;5:1137–46.

  2. Bojarowicz H, Płowiec A. Influence of vitamin A on skin condition. Probl Hig Epidemiol. 2010;91:352–6.

  3. Nyirady J, Lucas C, Yusuf M, et al. The stability of tretinoin gel microsphere 0.1% Cutis. 2002;70:295–8.

  4. Ascenso A, Ribeiro H, Marques HC, et al. Is tretinoin still a key agent for photoaging management? Mini Rev Med Chem. 2014;14:629–41.

  5. Scientific Committee of Consumer Safety – SCCS. Rousselle C. Opinion of the Scientific Committee on Consumer Safety (SCCS) e Final version of the Opinion on Vitamin A (retinol, retinyl acetate and retinyl palmitate) in cosmetic products. Regul Toxicol Pharmacol. 2017;84:102–4.

  6. Creidi P, Humbert P. Clinical use of topical retinaldehyde on photoaged skin. Dermatology. 1999;199:49–52.