Understanding Retinol Tolerance

Vitamin A and its derivatives can be found in many skin care products as they are some of the best treatments available for the prevention of aging, right after sunscreen.[i] Tretinoin is a natural retinoid available as a prescription, and tazarotene and adapalene are synthetic retinoids. There are many over-the-counter options as well that contain retinol and retinyl esters. An example is the Zo product line. These products are easy to use and ideal for those seeking a fresher appearance.

Retinoids bind to the nuclear receptors in cells and modulate their gene expression for processes like cellular differentiation and proliferation. This causes normalisation of cell keratinisation, wherein the outermost layer of cells on the epidermis are replaced by keratin.[ii] Most people do not stick to continuous retinoid use because of their side effects, but these can overcome with proper use.

Benefits of Topical Retinoids

Kligman and Willis introduced the first topical retinoids in 1975. They observed the beneficial properties of retinoids to include reduction of wrinkles, roughness, and improvement in uneven skin tone. Histology also revealed that retinoids could reduce corneocyte adhesion and epidermal hyperplasia. In contrast, they increase collagen and elastin synthesis, which contributes to the renewed look of the face. Five years later, it was discovered that retinoids also block collagenase activity, reducing collagen degradation.[iii][iv]

Most literature discusses tretinoin when retinoids are mentioned, and the benefits of vitamin A for the skin – retinoids increase cell turnover of the epidermis, promoting the loss of pigment on the surface and evening out the skin tone. Over the years, clinical trials have reproduced many findings regarding retinoids, and these findings are the scientific basis for why these ingredients are so frequently recommended by dermatologists.

Retinoids must be used continuously, as results typically become apparent after approximately three months of regular use, with the exception of smooth skin. [v] Using the product long-term is necessary to maintain results, and retinoids can be used indefinitely. The exception is pregnant and breastfeeding individuals, who must stop treatment as retinoids exert teratogenic effects on fetuses.[vi]

Patient Tolerability

An unfortunate aspect of retinoids is that their use results in retinoid dermatitis in 95% of patients. This presents as redness, flaking, and sensitivity, all of which deter patients and limit long-term compliance.[vii] Retinol has similar cellular changes to retinoid acid, but the side effects are often milder.[viii] Studies have compared the two compounds, and it is generally thought that retinol exerts the same effects at a lower intensity. The reduction in severe side effects is what attracts patients to retinol.

To increase compliance rates, treatment should be personalized to patients, who must be counselled regarding the dermatitis. [ix] Scaling and stinging are also normal and indicate that the product has been adequately dosed. If necessary, the application frequency may be adjusted to reduce side effects. This can be determined by the patient with some guidance from their dermatologist.

Tips for Compliance

The following are tips adapted from the original Tretinoin guidelines by Kligman:

  • Treatment should begin at a low retinol concentration, and can be increased over time. The ideal starting point is 0.3% retinol.[x]
  • Patients should cleanse in the morning and night with clean hands and warm water, and apply retinoids after thoroughly drying the skin. Moisturizer should be used in the morning.
  • Retinoids should be used at night because they are photosensitizing. A small, pea sized amount is enough. Stinging indicates enough product has been used.[xi]
  • Moisturizer reduces peeling and should also be used on days when the retinoid is not used. At night, moisturizer should be applied 30 minutes after the retinoid to avoid dilution.
  • Introduce retinol into the skincare regimen slowly. Application should be tapered if patients have sensitive skin. Short-contact therapy, where the patient washes the product off after 30 minutes, can be used.[xii]
  • Retinoids can be used on hands and forearms but should not be used near the eyes and lips because they are so sensitive. Some brands do offer eye products created with low strength retinol. To treat the décolletage, apply the product once every three nights.[xiii]
  • Many patients will experience retinoid dermatitis, which typically lasts for approximately one month – patients should know this is normal and not a reason to quit treatment.
  • Doses may be increased after three months in slow increments. Eventually, a prescription may be given by a dermatologist, but irritation and dryness may occur because they are much higher strength products.
  • Patients must wear sunscreen with a minimum of 30 SPF due, as the thinning of the stratum corneum will make them more susceptible to sun damage. Harsh exfoliants and peels should be avoided.
  • Results will be evident after three months of use, and maintenance is required to continue seeing results. After eight months, product use can be tapered to twice per week.

Conclusions

Retinoids and over-the-counter retinols may improve the skin’s appearance and restore a youthful complexion by increasing smoothness and improving pigmentation. Retinols do not cause as much irritation as Tretinoin and provide similar effects. With Tretinoin, retinoid dermatitis is unavoidable but resolves quickly. Patients should be counselled about side effects and proper product use to increase overall compliance and achieve their desired results.

[i] Serri, R., & Iorizzo, M. (2008). Cosmeceuticals: focus on topical retinoids in photoaging. Clinics in Dermatology, 26(6):633-5.

[ii] Serri, R., & Iorizzo, M. (2008). Cosmeceuticals: focus on topical retinoids in photoaging. Clinics in Dermatology, 26(6):633-5.

[iii] Fisher, G.J., Reddy, A.P., Datta, S.C., et al. (1995). All-trans retinoic acid induces cellular retinol-binding protein in human skin in vivo. J Investig Dermatol, 105:80-6.

[iv] Fisher, G.J., Datta, S.C., Talwar, H.S., et al. (1996). Molecular basis of sun-induced premature skin ageing and retinoid antagonism. Nature, 379:335-9.

[v] Serri, R., & Iorizzo, M. (2008). Cosmeceuticals: focus on topical retinoids in photoaging. Clinics in Dermatology, 26(6):633-5.

[vi] Serri, R., & Iorizzo, M. (2008). Cosmeceuticals: focus on topical retinoids in photoaging. Clinics in Dermatology, 26(6):633-5.

[vii] Serri, R., & Iorizzo, M. (2008). Cosmeceuticals: focus on topical retinoids in photoaging. Clinics in Dermatology, 26(6):633-5.

[viii] Kong, R., Cui, Y., Fisher, G.J., et al. (2016).  A comparative study of the effects of retinol and retinoic acid on histological, molecular, and clinical properties of human skin. Journal of Cosmetic Dermatology, 15(1):49-57.

[ix] Kligman, A.M. (1989). Guidelines for the use of topical tretinoin (Retin-A) for photoaged skin. J Am Acad Dermatol, 21:650-4.

[x] Kligman, A.M. (1989). Guidelines for the use of topical tretinoin (Retin-A) for photoaged skin. J Am Acad Dermatol, 21:650-4.

[xi] Kligman, A.M. (1989). Guidelines for the use of topical tretinoin (Retin-A) for photoaged skin. J Am Acad Dermatol, 21:650-4.

[xii] Kligman, A.M. (1989). Guidelines for the use of topical tretinoin (Retin-A) for photoaged skin. J Am Acad Dermatol, 21:650-4.

[xiii] Kligman, A.M. (1989). Guidelines for the use of topical tretinoin (Retin-A) for photoaged skin. J Am Acad Dermatol, 21:650-4.