Main Issue September 2012

Topical Anti-aging Skin Care: Product Recommendation and Therapeutic Compliance

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Advanced cosmetic procedures, such as dermal fillers, neurotoxins, and laser therapies, continue to reshape the approach to minimally-invasive facial rejuvenation in the dermatology clinic. These products and procedures can be used alone or in combination for improvement of wrinkling, scarring, and volume loss. But not all patients are ready for cosmetic procedures—even minimally invasive ones—and those patients who undergo procedures may still have complaints of uneven skin texture or tone and fine wrinkling after treatment.

The gold standard prescription topical treatment for facial fine lines is topical tretinoin, in conjunction with a comprehensive skin care regimen that includes sunscreen. Along with comprehensive skin care, topical tretinoin can be used as a primary treatment for facial fine lines. Many dermatologists also use it to support and maintain the results of cosmetic procedures. Increasingly, patients seek to augment their topical prescription wrinkle-reducing regimen with formulations containing topical antioxidants, peptides, and/or botanicals. While many anti-aging topical cosmeceutical products can be used in conjunction with topical tretinoin, generally, it is best to apply additional agents in the morning and not in combination with tretinoin. There is a lack of studies on combination approaches, and it is not known whether certain antioxidants, vitamins, or other ingredients are compatible with tretinoin.

Dermatology clinicians should be prepared to provide product guidance to their patients. The following review of the use of tretinoin for topical wrinkle reduction and other popular ingredients in topical rejuvenating products can help direct patient education and product recommendation.

Skin Aging: A Review

Skin aging is attributed to both intrinsic and extrinsic factors. Among extrinsic factors (which include exposure to cigarette smoke and other chemicals), UV radiation is probably the most prevalent and significant. Chronic UV exposure increases the risk for melanoma and non-melanoma skin cancer and promotes photoaging—characterized by leathery texture, wrinkles, laxity, and sallowness. Evidence suggests that up to 50 percent of the cutaneous damage caused by UV exposure is via free-radical formation,1,2 which leads to oxidative stress or immunosuppression. UV exposure is known to induce matrix metalloproteinases (MMP) that degrade collagen.3 UV exposure is also linked to the development of senile lentigines4 and activation of melanocytes, resulting in mottled hyperpigmentation.5

Natural changes also take place in the skin with advancing age; chronologically older skin demonstrates a thickening of the stratum corneum and a thinning of the epidermis, compared to younger skin.6

The Anti-Aging Cornerstones

There are two primary strategies for management of photoaging: prevention and treatment. Despite the number of prescription and cosmeceutical products currently marketed to treat signs of photodamage, no single topical intervention is as essential as a broad-spectrum sunscreen with an SPF higher than 15, preferably 30 or higher, for prevention. In addition to UV avoidance and physical protection strategies, patients must regularly and appropriately apply a broad-spectrum sunscreen to reduce the amount of UVA and UVB radiation that reaches the skin to induce the molecular processes that contribute to the appearance of aging.7

In terms of topical treatment, tretinoin remains the prescription agent of choice for treating fine lines and wrinkles. It has been approved in the context of a comprehensive skin care and sunlight avoidance program. Use of tretinoin has been documented to encourage increased production of procollagen and formation of new collagen;6 It is shown to thin the stratum corneum and thicken the epidermis.8 It also decreases melanosome transfer and inhibits UV-B stimulated tyrosinase activity and melanin synthesis.9 These changes are associated with a reduction in the appearance of hyperpigmentation and lentigines.10

Application of tretinoin is associated with local cutaneous irritation, erythema, and/or peeling and drying,11 which are most notable at the initiation of therapy and generally subside with continued use. Patients must be educated about the risk for irritation and the need for adherence with a long-term topical treatment plan. In clinical trials of topical tretinoin 0.02% cream (Renova, Valeant Dermatology) for photodamage, patients who discontinued therapy demonstrated a loss of clinically-appreciable treatment benefits.

Patients can take steps to minimize irritation associated with the introduction of therapy. Concomitant use of topical moisturizers, especially in the morning, can help reduce any dryness or irritation associated with nightly tretinoin application.

All patients should also use bland skincare, including soapfree cleansers, especially during the initiation phase. Those who wish to try other cleansers may consider doing so when they are fully accustomed to tretinoin use.

Another option to improve tolerability is to titrate tretinoin therapy gradually, beginning with application just a few times per week and increasing to nightly use.

“Anti-aging” Cosmeceuticals

Popular agents that can be incorporated into non-prescription topical “anti-aging” skin care products include antioxidants, such as vitamin E and C, coenzyme Q10, alpha-lipoic acid, glutathione, green tea, dehydroepiandrosterone, melatonin, selenium and resveratrol. 12 Peptides, hydroxyl acids, sugar amines, and ceramides are also commonly marketed, too.13 Other prescription agents, such as hydroquinone and azelaic acid are also used to manage pigmentary changes associated with aging.12 Over-the-counter formulations generally appear to work more to prevent UV-induced skin damage. As such, they may complement the effects of topical tretinoin as part of the patient’s skin care regimen.12

One challenge of cosmeceutical product selection is a general lack of published data on specific formulations, although in many cases there are studies (of varying levels of quality) suggesting that specific topical agents may confer benefits to reduce the appearance of signs of photodamage. Among the most promising topicallyapplied ingredients currently recommended by cosmetic dermatologists are antioxidants, botanicals, and peptides.

Given their potential activity in helping to prevent or minimize UV-induced damage, these various ingredients are increasingly being incorporated into formulations with sunscreen ingredients. This makes them well-suited for morning application and, as a practical consideration, a reasonable complement to nightly tretinoin use. There are also standard or non-sunscreening moisturizing formulations containing antioxidants, botanicals, and/ or peptides that can be used by patients who prefer to use two different products: a distinct sunscreen and a cosmeceutical.

Antioxidants provide protection from endogenous and exogenous oxidative stresses, and studies indicate potential cutaneous benefit when these agents are incorporated into sunscreens and skin care products.1,14,15 Topically-applied antioxidants are thought to prevent the damage created by UV-generated free radicals.1,16,17

One area of continued research is the optimal “dosage” of antioxidants and ideal combinations. Research indicates that some combinations of topically applied antioxidants, such as vitamin E and vitamin C, may provide greater benefit than the antioxidants applied individually.1 Data on peptides are less extensive, but they are widely believed to provide benefits, though not of the level associated with prescription topical therapies.18

A growing trend in the cosmeceutical field is the development of formulations intended to provide benefits in specific disease states. These formulations may be used in complement to topical retinoids and, very often, appear to be appropriate for use in conjunction with disease-targeted prescription therapies. For example, Pro+TherapyMD Advanced Ultra Light Day Repair SPF 30 (Valeant), is a newer formulation that offers “sheer zinc,” a form of the physical sunscreen that can be used on dark skin tones. In addition to a proprietary blend of ceramides for moisturization, botanically derived Kinetin and Zeatin target specific features of the skin of rosacea patients. Unpublished data suggest that Zeatin improved skin roughness by 86 percent, while Kinetin improved redness, roughness, and blotchiness associated with rosacea by 80 percent. Note that these signs of improvement are not indicative of direct disease treatment, as the products are not drugs.

Any disease-targeted cosmeceutical formulation should not be applied at the same time as topical prescription agents. For some patients, the cosmeceutical may become a skin care maintenance agent for use once the prescription drug is withdrawn.

Long-Term Strategies

Skin aging is the result of both natural—and unstoppable— intrinsic factors and the cumulative influence of extrinsic factors. As such, it is a persistent and progressive process. It is impossible to completely reverse or prevent skin aging, but the process can be slowed and the appearance of skin aging can be reduced. Topical tretinoin is a safe and effective topical prescription intervention shown to reduce the clinical and histological effects of photoaging and chronological aging. As monotherapy, it is most appropriate for patients with early signs of skin aging, including the patient in her (or his) thirties or forties.

Remember that topical cosmeceutical products should be used within a comprehensive skin care regimen when also using topical tretinoin. These formulations, commonly featuring botanicals, antioxidants, and/or peptides, are generally thought to offset the negative effects of UV exposure and, as such, confer a protective effect that may complement the effects of tretinoin. Both prescription and OTC agents are used in conjunction with aesthetic procedures. Finally, all patients—and especially those concerned about signs of skin aging—must use a broad-spectrum sunscreen daily and practice UV avoidance.

Patients must be prepared to adhere to therapy over their lifetime in order to achieve and maintain improvement in the signs of skin aging. With proper education and guidance from the clinician, patients can work with their dermatology care provider to develop a topical wrinkle-reduction and rejuvenation regimen they like using and that provides notable cosmetic improvements.

  1. Chen L, Hu JY, Wang SQ. The role of antioxidants in photoprotection: A critical review. J Am Acad Dermatol. 2012 Mar 9. doi:10.1016/j.jaad.2012.02.009.
  2. Black HS. Potential involvement of free radical reactions in ultraviolet light-mediated cutaneous damage. Photochem Photobiol 1987; 46(2):213-21.
  3. Photochem Photobiol. 1999 Feb;69(2):154-7. Molecular mechanisms of photoaging in human skin in vivo and their prevention by all-trans retinoic acid. Fisher GJ, Talwar HS, Lin J, Voorhees JJ.
  4. Hölzle E. Pigmented lesions as a sign of photodamage. Br J Dermatol. 1992 Sep;127 Suppl 41:48-50.
  5. Ortonne JP. The effects of ultraviolet exposure on skin melanin pigmentation. J Int Med Res. 1990;18 Suppl 3:8C-17C.
  6. Skin Pharmacol. 1993;6 Suppl 1:70-7. Topical retinoic acid for photoaging: clinical response and underlying mechanisms. Griffiths CE, Voorhees JJ.
  7. Antoniou C, Kosmadaki MG, Stratigos AJ, Katsambas AD. Photoaging: prevention and topical treatments. Am J Clin Dermatol. 2010;11(2):95-102.
  8. Cutis. 2005 Feb;75(2 Suppl):10-3; discussion 13. The mechanism of action of topical retinoids. Kang S.
  9. Ortonne JP. Retinoid therapy of pigmentary disorders. Dermatol Ther. 2006 Sep- Oct;19(5):280-8.
  10. Kang HY, Valerio L, Bahadoran P, Ortonne JP. The role of topical retinoids in the treatment of pigmentary disorders: an evidence-based review. Am J Clin Dermatol. 2009;10(4):251-60.
  11. Arch Dermatol. 1995 Sep;131(9):1037-44. Two concentrations of topical tretinoin (retinoic acid) cause similar improvement of photoaging but different degrees of irritation. A double-blind, vehicle-controlled comparison of 0.1% and 0.025% tretinoin creams. Griffiths CE, Kang S, Ellis CN, Kim KJ, Finkel LJ, Ortiz-Ferrer LC, White GM, Hamilton TA, Voorhees JJ.
  12. Puizina-Ivić N, Mirić L, Carija A, Karlica D, Marasović D. Modern approach to topical treatment of aging skin. Coll Antropol. 2010 Sep;34(3):1145-53.
  13. Bissett DL. Common cosmeceuticals. Clin Dermatol. 2009 Sep-Oct;27(5):435-45.
  14. Bogdan Allemann I, Baumann L. Antioxidants used in skin care formulations. Skin Therapy Lett. 2008; 13(7):5-9.
  15. Fuchs J. Potentials and limitations of the natural antioxidants RRR-alpha-tocopherol, L-ascorbic acid and beta-carotene in cutaneous photoprotection. Free Radic Biol Med. 1998; 25(7):848-73.
  16. Masaki H. Role of antioxidants in the skin: anti-aging effects. J Dermatol Sci. 2010; 58(2):85-90.
  17. Pillai S, Oresajo C, Hayward J. Ultraviolet radiation and skin aging: roles of reactive oxygen species, inflammation and protease activation, and strategies for prevention of inflammationinduced matrix degradation - a review. Int J Cosmet Sci. 2005; 27(1):17-34.
  18. Draelos ZD, Ertel KD, Berge CA. Facilitating facial retinization through barrier improvement. Cutis. 2006; 78(4):275-81.

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