Efficacy and Tolerability of a Skin Brightening/Anti-Aging Cosmeceutical Containing Retinol 0.5%, Niacinamide, Hexylresorcinol, and Resveratrol

July 2016 | Volume 15 | Issue 7 | Original Article | 863 | Copyright © July 2016

Patricia Farris MD,a Joshua Zeichner MD,b and Diane Berson MDc

aTulane University Medical Center, New Orleans, LA
bMount Sinai Hospital, New York, NY
cWeill Medical College of Cornell University, New York Presbyterian Hospital, New York, NY

Consumers are increasingly interested in over-the-counter skin care products that can improve the appearance of photodamaged and aging skin. This 10-week, open-label, single- center study enrolled 25 subjects with mild to moderate hyperpigmentation and other clinical stigmata of cutaneous aging including fine lines, sallowness, lack of clarity, and wrinkling. Their mean age was 53.4±7.7 years. The test product contained retinol 0.5% in combination with niacinamide 4.4%, resveratrol 1%, and hexylresorcinol 1.1% in a moisturizing base. Subjects were provided a skin care regimen including a cleanser, hydrating serum, moisturizer, and an SPF 30 sunscreen for daily use. The test product was applied only at night.

The use of this skin brightening/anti-aging cosmeceutical was found to provide statistically significant improvements in all efficacy endpoints by study end. Fine lines, radiance, and smoothness were significantly improved as early as week 2 (P<.001). By week 4, hyperpigmentation, overall skin clarity, evenness of skin tone, and wrinkles showed statistically significant improvement compared to baseline. Mild retinoid dermatitis including flaking and redness occurred early in the study as reflected by tolerability scores. By week 10, subjects reported no stinging, itching, dryness, or tingling.

The results of this open-label clinical study suggest that a topical cream containing retinol 0.5% in combination with niacinamide, resveratrol, and hexylresorcinol is efficacious and tolerable for skin brightening/anti-aging when used with a complementary skin care regimen including SPF 30 sun protection.

J Drugs Dermatol. 2016;15(7):863-868.


Sallowness, roughness, uneven pigmentation, coarse lines, and wrinkles are all visible signs of photoaging. Prescription retinoids such as tretinoin and tazarotene have demonstrated efficacy for treating photoaged skin in numerous clinical trials studies.1-3 Clinical benefits include smoother skin, reduction in lines and wrinkles, and more even skin tone. The use of prescription retinoids in some patients is limited by their propensity to cause skin irritation including redness and flaking.
The gold standard for skin lightening is hydroquinone (HQ) 4%. Available only by prescription, patients have limited access to HQ 4% and often seek lower cost over the counter options. Additionally, consumer concerns about the safety of hydroquinone leave many looking for lightening products that may be perceived as more “natural” and gentle on the skin.
Excellent skin lightening results are obtainable by combining synergistic individual components. Examples include the well-known Kligman formulation for the treatment of melasma which contained tretinoin 0.1%, HQ 5.0%, and dexamethasone 0.1%.4 The commercialized product TriLuma® Cream, (Galderma Laboratories, Fort Worth, Texas) includes tretinoin 0.05%, HQ 4.0%, and fluocinolone acetonide 0.01%. Clinical studies demonstrated that this product is an effective skin lightener improving hyperpigmentation in patients with melasma.5 TriLuma was approved by the FDA in 2002 for the treatment of moderate to severe melasma and is now commonly used off-label to treat photoaged skin.
The brightening/anti-aging test product evaluated in this study contains the synergistic combination of retinol (ROL) 0.5%, niacinamide 4.4%, resveratrol 1%, and hexylresorcinol 1.1%. Collectively, these ingredients act on the melanin pathway in different ways at the same time, improving the product’s effect as a skin lightening agent. Additionally, these ingredients have been shown to confer significant anti-aging benefits.
ROL is a non-prescription retinoid that has been shown to improve aging skin, but is associated with less irritation than prescription alternatives.6 ROL is oxidized into retinaldehyde (RAL) in the skin then further oxidized into retinoic acid or tretinoin, which is the biologically active molecule. Kang et