Vitamin A has been in existence since the early 1900s. It was first clearly recognized in 1913, with its chemical nature being established in 1933. Vitamin A derivatives were then synthesized in 1947, and has since been classified into three generations1:
- The first generation of vitamin includes retinol, retinal, isotretinoin and retinoic acid
- Acitretin and etretinate comprise second generation retinoids
- The third generation consists of adapalene and tazarotene (*note: the compounds found in this generation have a more rigid structure than their predecessors, one which enables them to bind to a narrower set of receptors1,2).
Retinoic acid and retinols
Tretinoin is a synthetic retinoic acid approved by the Food and Drug Administration (FDA) via prescription, whilst retinols comprise of non-prescription vitamin A derivatives (commonly used in cosmetic skin care practices).
For the sake of this article, over the counter (OTC) retinoids that are found in cosmeceuticals will be collectively referred to as retinols.
Topical tretinoin in dermatology
Topical tretinoin has been approved for use in dermatology for over 50 years. During this time, it has accumulated significant efficacy data – in not only the management of acne vulgaris and photo-damaged skin – but also in the demonstration of clinical potential for treating a wide variety of other skin conditions. 4,5
That being said, retinols should not be considered as a form of medication, as it is not classified under medicine. It does, however, require conversion to active retinoic acid in order to demonstrate activity.6 And while several studies have demonstrated that retinol may induce the same cellular and molecular action as tretinoin, a 20-fold higher dose is still required.7
As to the use of retinols in cosmetics, they are found to be stable in a cosmetic formulation, yet only if processed under inactive atmospheric conditions and then stored, for example, in aluminium tubes at less than 20o Celsius.7 Additionally, the impact of the vehicle on penetration and retinol stability must also be considered, as these factors play a crucial role.8
Tolerability
Topical administration of retinoids – in particular tretinoin – is frequently associated with dry, scaly, flaky, itchy, burning skin. These incidences can occur in up to 90% of patients with topical tretinoin use, with symptoms appearing within a few days, and lasting up to three months before declining (despite continued application of the drug).9 One method of reducing retinoid irritation while simultaneously reducing tactile roughness, is the liberal use of effective moisturisers that can smooth flaky skin scale and improve barrier disruption.
In my practice, I recommend preparing the skin prior to the commencement of topical tretinoin by ensuring strict sunscreen protection, gentle cleanser use, and generous moisturising – especially in patients who have a predisposition to skin conditions such as eczema, rosacea and sensitivity.
How to minimise potential irritation:
- Treatment is initiated 1-2 times a week at night, which is then gradually increased in frequency
- It is recommended to eliminate the use of harsh cleansers and exfoliating scrubs, followed by a 10 minute wait after cleansing before applying tretinoin
- A pea sized amount should suffice for the entire facial surface area, observing caution near mucous membranes
- Because tretinoin should be applied evenly, spot treatment is discouraged
- Daily sun protection with a minimum SPF 30 is advised
- Short contact application of tretinoin can also be considered
- Consistency is key, however, if pronounced irritation is perceived, then tretinoin must be discontinued
Indications:
- Photo-damaged and photo-ageing skin
Treatment of photo-damaged skin has escalated in the last few years, with many therapies remaining unproven in efficacy, unapproved, or only supported with limited clinical evidence.10 Topical tretinoin, on the other hand, has been established as the gold standard for the treatment of photo-damaged skin,11as it’s the most extensively studied compound that has proven to have the ability to reduce fine lines, superficial wrinkles, mottled hyperpigmentation, freckles and sallowness.12
- Acne vulgaris
Due to their nuclear RAR binding ability, topical retinoids are successful in the targeting of various causes and subsequent developmental factors related to acne. This wide spectrum anti-acne activity and safety profile (with no risk of inducing bacterial resistance) justifies their use as first line treatment in most types of acne.14
- Pigmentary disorders
Meanwhile, topical tretinoin appears to have a positive impact on pigmentation, as seen by a decrease in dermal freckling. In fact, Bulengo-Ransby et al demonstrated that tretinoin 0,1% significantly lightened post-inflammatory hyperpigmentation.16 In melasma, tretinoin suppresses tyrosinase activity, while accelerating epidermal turnover at the same time. This process ultimately results in the rapid dispersment of melanin.
Conclusion
Topical tretinoin is an addition to the arsenal of dermatologic therapeutic options. It has been universally utilised as an evidence-based, off-label application for a multitude of skin conditions. Conversely, it’s important to note that the first line of treatment for various dermatoses should always be an approach that is tailor-made to an individual’s indication, as each patient impact varies with skin condition, vehicle formation, mode and frequency of application, moisturiser use and environmental factors.
Disclaimer: This article was commissioned by Rite Aid Health Care. Content is written by Dr Ayesha Moolla, whereby she shares her professional experience, knowledge and thoughts on the use of topical tretinoin for the treatment of various skin concerns. Rite Aid is the distributor of medical-grade retinol in South Africa available by prescription only. Due to medical regulations in South Africa, we are unable to publish the names of scheduled medicines. Contact Rite Aid for more info (+27) 011 325 2686 / info@riteaid.co.za or speak to your doctor.
References
- Khalil S, Bardawil T, Stephan C, Darwiche N, Abbas O, Kibbi AG, Nemer G, Kurban M. Retinoids: a journey from the molecular structures and mechanisms of action to clinical uses in dermatology and adverse effects. J Dermatolog Treat. (2017) Dec;28(8):684-696.
- Spierings NMK. Evidence for the Efficacy of Over-the-counter Vitamin A Cosmetic Products in the Improvement of Facial Skin Aging: A Systematic Review. J Clin Aesthet Dermatol. 2021 Sep;14(9):33-40.
- Connor MJ, Smit MH. The formation of all-trans-retinoic acid from all-trans-retinol in hairless mouse skin. Biochem Pharmacol. 1987 Mar 15;36(6):919-24.
- Thorne EG. Topical tretinoin research: an historical perspective. J Int Med Res. 1990;18 Suppl 3:18C-25C.
- Baldwin HE, Nighland M, Kendall C, Mays DA, Grossman R, Newburger J. 40 years of topical tretinoin use in review. J Drugs Dermatol. 2013 Jun 1;12(6):638-42.
- Kurlandsky SB, Xiao JH, Duell EA, Voorhees JJ, Fisher GJ. Biological activity of all-trans retinol requires metabolic conversion to all-trans retinoic acid and is mediated through activation of nuclear retinoid receptors in human keratinocytes. J Biol Chem. 1994 Dec 30;269(52):32821-7.
- Opinion of the Scientific Committee on Consumer Safety (SCCS) – Final Version of the Opinion on Vitamin A (retinol, retinyl acetate and retinyl palmitate) in Cosmetic products. Regul Toxicol Pharmacol 2017 Mar; 84:102.
- Mukherjee S, Date A, Patravale V, Korting HC, Roeder A, Weindl G. Retinoids in the treatment of skin aging: an overview of clinical efficacy and safety. Clin Interv Aging. 2006;1(4):327-48
- Noble S, Wagstaff AJ. Tretinoin. A review of its pharmacological properties and clinical efficacy in the topical treatment of photodamaged skin. Drugs Aging. 1995 Jun;6(6):479-96.
- Ting W. Tretinoin for the treatment of photodamaged skin. Cutis. 2010 Jul;86(1):47-52.
- Kircik LH. Histologic improvement in photodamage after 12 months of treatment with tretinoin emollient cream (0.02%). J Drugs Dermatol. 2012 Sep;11(9):1036-40.
- Kang S, Bergfeld W, Gottlieb AB, Hickman J, Humeniuk J, Kempers S, Lebwohl M, Lowe N, McMichael A, Milbauer J, Phillips T, Powers J, Rodriguez D, Savin R, Shavin J, Sherer D, Silvis N, Weinstein R, Weiss J, Hammerberg C, Fisher GJ, Nighland M, Grossman R, Nyirady J. Long-term efficacy and safety of tretinoin emollient cream 0.05% in the treatment of photodamaged facial skin: a two-year, randomized, placebo-controlled trial. Am J Clin Dermatol. 2005;6(4):245-53.
- Fisher GJ, Datta SC, Talwar HS, Wang ZQ, Varani J, Kang S, Voorhees JJ. Molecular basis of sun-induced premature skin ageing and retinoid antagonism. Nature. 1996 Jan 25;379(6563):335-9
- 14. Thielitz A, Gollnick H. Topical retinoids in acne vulgaris: update on efficacy and safety. Am J Clin Dermatol. 2008;9(6):369-
- Jain S. Topical tretinoin or adapalene in acne vulgaris: an overview. J Dermatolog Treat. 2004 Jul;15(4):200-7.
- Bulengo-Ransby SM, Griffiths CE, Kimbrough-Green CK, Finkel LJ, Hamilton TA, Ellis CN, Voorhees JJ. Topical tretinoin (retinoic acid) therapy for hyperpigmented lesions caused by inflammation of the skin in black patients. N Engl J Med. 1993 May 20;328(20):1438-43.
- Bandyopadhyay D. Topical treatment of melasma. Indian J Dermatol. 2009;54(4):303-9.
- Bhawan J, Gonzalez-Serva A, Nehal K, Labadie R, Lufrano L, Thorne EG, Gilchrest BA. Effects of tretinoin on photodamaged skin. A histologic study. Arch Dermatol. 1991 May;127(5):666-72. Erratum in: Arch Dermatol 1991
1https://www.britannica.com/science/vitamin-A
Dr Ayesha Moolla qualified as a medical doctor at UKZN in 1992. After working in general practice for 5 years, she then worked as a medical officer for The Dept of Health, City of Durban. After her move to Cape Town, she worked as a medical officer at the UCT Student Health Centre, as well as in the Department of Rheumatology, Groote Schuur Hospital. Dr Moolla completed her post graduate studies in Dermatology at Stellenbosch University and Tygerberg Hospital and received her Masters Degree in Medicine in the field of dermatology (MMed Derm) in 2009. Dr Moolla has since commenced private practice at Gatesville Medical Centre. She also consults part time at Bellville Medical Centre. She has a special interest in psoriasis, dermatitis and paediatric dermatology.