Cosmeceutical Recommendations for Diverse Skin Types

At the 2021 Skin of Color Update, Dr. Heather Woolery-Lloyd, Director of the Skin of Color Division at the University of Miami Department of Dermatology,  delivered an excellent talk on cosmeceutical recommendations for patients with diverse skin types, a personal favorite subject of hers. Catch the pearls of her talk here!

Hot Topics  in Cosmeceuticals

Topical Cannabinoids – The skin has its own endocannabinoid system with receptors present in the epidermis, sebaceous glands, hair follicles, sweat glands and sensory nerves. Cannabidiol (CBD) may have a role in decreasing the activity of T helper cells and interferon gamma.  Skin property studies have shown that topical cannabinoids reduce erythema and sebum production.¹ Interestingly, they may also play a role in skin aging – genetic deletion of cannabinoid type 1 receptors in mice has demonstrated early onset aging of the skin.²

Bakuchiol – Derived from babchi seed oil, this is a retinoid-like substance that upregulates collagen. In a randomized, double-blind study patients were treated with either bakuchiol 0.5% cream twice daily or retinol 0.5% cream daily. Bakuchiol and retinol both significantly decreased the wrinkle surface area and hyperpigmentation with scaling and stinging reported in the retinol group.³

Polyhydroxyacids (PHAs) – These were initially discovered in the 1970s but have gained popularity recently. They offer similar benefits to alpha-hydroxy acids but are less irritating, more moisturizing and can help with skin barrier function. Examples are gluconolactone and lactobionic acid (which may reduce matrix metalloproteinases).^4,5

Cosmeceuticals for Hyperpigmentation – Hydroquinone alternatives

Vitamin C – A randomized double-blind study evaluated 5% vitamin C vs 4% hydroquinone for the treatment of melasma. Although both treatments worked, hydroquinone worked better and vitamin C was better tolerated with less side effects.⁶Another split-face study compared microneedling with tranexamic acid vs microneedling with vitamin C in the treatment of melasma. While both treatments worked, tranexamic acid did have a trend of working slightly better.⁷ A third randomized placebo-controlled trial of Vitamin C iontophoresis in melasma demonstrated benefit of vitamin C.⁸

Licorice – Liquiritin is an extract of Licorice that is particularly known for hyperpigmentation. One study evaluating 2% liquiritin, topical 4% liquiritin and topical 4% hydroquinone in the treatment of melasma. In this study the liquiritin outperformed hydroquinone.⁹ Another study evaluated liquiritin alone vs liquiritin combined with vitamin C, and the combination topical was shown to be of benefit in melasma.¹⁰

Niacinamide – Dr. Woolery-Lloyd likes to use Niacinamide in her practice, particularly moisturizers with Niacinamide. Usual percentages are between 2-4% and it is often combined with other lightening agents.

Azelaic Acid – Several large studies have evaluated 20% Azelaic acid vs hydroquinone in the treatment of melasma.¹¹ As a clinical pearl, Dr. Woolery-Lloyd recommends combining Azelaic acid with a moisturizer or an anti-inflammatory in order to improve tolerability (it can be drying).

Silymarin – An antioxidant that is common in a lot of anti-aging formulas. In a study of 42 subjects with melasma, 14 patients were treated with silymarin 0.7% cream, 14 patients were treated with silymarin 1.4% cream and the third arm of patients were treated with 4% hydroquinone cream. Melasma Area and Severity Index (MASI) scores were significantly reduced in all groups, and the hydroquinone was associated with more adverse effects.¹²

Thiamidol – This ingredient was recently introduced in European markets and is a tyrosinase inhibitor. A split face study evaluated BID vs QID use, and hyperpigmentation, skin roughness and MASI scores all improved significantly compared to baseline, and the 4 times a day application led to significant improvement and was well tolerated.¹³

Cysteamine – Cysteamine is another ingredient that Dr. Woolery-Lloyd keeps in her toolbox. A recent study of patients with melasma evaluated treatment with 5% cysteamine or a modified kligman formula (4% hydroquinone, 0.05% retinoic acid, 0.1% betamethasone). After 2 months and 4 months, there was a 9% greater reduction in the MASI score in the cysteamine group vs the kligman formula.¹⁴

Tranexamic acid – Can be used orally, topically, intradermally, or in conjunction with microneedling. In a study of 100 Korean women with melasma, 5% tranexamic acid was delivered intradermally at 4mg/mL weekly for 12 weeks with a significant decrease in MASI scores.¹⁵ In another study, patients were randomized to three groups: topical 1.8% liposomal tranexamic acid twice daily vs. microneedling with a 5% tranexamic solution weekly vs 2% hydroquinone nightly. Microneedling with tranexamic acid appeared to be the most effective modality in improvement of melasma.¹⁶

New Technology

Interestingly, there is new technology on the horizon with microneedle-like particles that may be able to bridge the gap between topical and microneedle delivery of active ingredients. This technology uses painless biocompatible microneedles in spreadable topical lotions, creams or patches. These microneedles are biocompatible and made of polyvinyl alcohol and sucrose or sodium hyaluronate.¹⁷ Current studies have evaluated the patch method of delivery, and further studies will hopefully evaluate delivery via lotions or creams.

Oral Agents

Polypodium Leucotomos – This is a topical fern plant and strong antioxidant that provides photoprotection. In a study that Dr. Woolery-Lloyd performed at the University of Miami, 21 subjects were randomized to polypodium leucotomos or placebo with a statistically significant improvement in melasma scores in patients who received polypodium leucotomos 240mg BID.¹⁸

Pycnogenol – This is a similar, lesser-known agent. In a double-blind, placebo-controlled study of 44 patients with melasma, patients were randomized to receive either 75mg pycnogenol or placebo twice a day for 60 days. Both groups also received tinted sunscreen and a topical triple combination cream at bedtime. While both groups exhibited a reduction in MASI scores, the reduction in scores and the colorimetric contrast were superior for the group treated with pycnogenol. Additionally, global investigator assessment improvement was greater in the pycnogenol group.¹⁹

In conclusion, the demand for cosmeceuticals in clinical practice continues to grow, and research is increasing and promising. Combining modalities may become the new gold standard in addition to incorporating oral agents to improve photoprotection.

References

1. 1. Sheriff, Tabrez, et al. “The potential role of cannabinoids in dermatology.” Journal of Dermatological Treatment 31.8 (2020): 839-845.
   2. Bilkei-Gorzo A, Drews E, Albayram O, et al. Early onset of aging-like changes is restricted to cognitive abilities and skin structure in Cnr1-/- mice. Neurobiol Aging. 2012;33(1):200.e11–22.
   3. Dhaliwal, S., et al. “Prospective, randomized, double-blind assessment of topical bakuchiol and retinol for facial photoageing.” British Journal of Dermatology 180.2 (2019): 289-296.
   4. Grimes, Pearl E., et al. “The use of polyhydroxy acids (PHAs) in photoaged skin.” Cutis 73.2 Suppl (2004): 3-13.
   5. Green, Barbara A., Brenda L. Edison, and Monya L. Sigler. “Antiaging effects of topical lactobionic acid: results of a controlled usage study.Cosmetic Deramgtology 21.2 (2008): 76-82.
   6. Espinal-Perez LE, Moncada B, Castanedo-Cazares JP. A double-blind randomized trial of 5% ascorbic acid vs. 4% hydroquinone in melasma. Int J Dermatol. 2004;43(8):604-607. doi:10.1111/j.1365-4632.2004.02134.x
   7. Menon A, Eram H, Kamath PR, Goel S, Babu AM. A Split Face Comparative Study of Safety and Efficacy of Microneedling with Tranexamic Acid versus Microneedling with Vitamin C in the Treatment of Melasma. Indian Dermatol Online J. 2019;11(1):41-45. Published 2019 Sep 26. doi:10.4103/idoj.IDOJ_22_19
   8. Huh CH, Seo KI, Park JY, Lim JG, Eun HC, Park KC. A randomized, double-blind, placebo-controlled trial of vitamin C iontophoresis in melasma. Dermatology. 2003;206(4):316-320. doi:10.1159/000069943
   9. Zubair, Shazia and Ghulam Mujtaba. “Comparison of efficacy of topical 2% liquiritin, topical 4% liquiritin and topical 4% hydroquinone in the management of melasma. Journal of Pakistan Association of Dermatology19 (2009): 158-163.
   10. Akram, Shamshad et al. “Efficacy of topical 4% liquiritin compared with topical 4% liquiritin mixed in 5% ascorbic acid in the treatment of melasma.” Journal of Pakistan Association of Dermatology23 (2016): 149-152.
   11. Baliña LM, Graupe K. The treatment of melasma. 20% azelaic acid versus 4% hydroquinone cream. Int J Dermatol. 1991;30(12):893-895. doi:10.1111/j.1365-4362.1991.tb04362.x
   12. Nofal, Ahmad, et al. “Topical silymarin versus hydroquinone in the treatment of melasma: A comparative study.” Journal of cosmetic dermatology 18.1 (2019): 263-270.
   13. Philipp-Dormston, W. G., et al. “Thiamidol containing treatment regimens in facial hyperpigmentation: An international multi-centre approach consisting of a double-blind, controlled, split-face study and of an open-label, real-world study.” International journal of cosmetic science 42.4 (2020): 377-387.
   14. Karrabi, Maryam, Jennifer David, and Mohammad Sahebkar. “Clinical evaluation of efficacy, safety and tolerability of cysteamine 5% cream in comparison with modified Kligman’s formula in subjects with epidermal melasma: A randomized, double-blind clinical trial study.” Skin Research and Technology 27.1 (2021): 24-31.
   15. Lee, Ji Ho, et al. “Localized intradermal microinjection of tranexamic acid for treatment of melasma in Asian patients: a preliminary clinical trial.” Dermatologic surgery 32.5 (2006): 626-631.
   16. Xing, Xiaoxue, et al. “The efficacy and safety of topical tranexamic acid (liposomal or lotion with microneedling) versus conventional hydroquinone in the treatment of melasma.” Journal of Cosmetic Dermatology 19.12 (2020): 3238-3244.
   17. Shin, Chong In, MunSik Kim, and Yeu-Chun Kim. “Delivery of Niacinamide to the Skin Using Microneedle-Like Particles.” Pharmaceutics 11.7 (2019): 326.
   18. Woolery-Lloyd, Martin, Caperton, Poster AAD 2012
   19. Lima, Paula Basso, et al. “French maritime pine bark extract (pycnogenol) in association with triple combination cream for the treatment of facial melasma in women: a double-blind, randomized, placebo-controlled trial.” Journal of the European Academy of Dermatology and Venereology 35.2 (2021): 502-508.

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