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Thyme

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Native to the western Mediterranean, Thymus vulgaris (one of approximately 300 Thymus species) is a small bush used for centuries as a spice and in medicine, particularly to treat bronchitis.¹Thymus species are among the wild and cultivated species used in traditional medicine in Bosnia and Herzegovina for various indications, including skin disorders.² Thyme essential oil is a natural compound generally recognized as safe by the Food and Drug Administration, with demonstrated antibacterial, antifungal, and antispasmodic activities.^3,4 Several other biologic activities have been associated with the polyphenol-rich herb, many of which have dermatologic implications. Notably, the essential oil of thyme and thymol, a key constituent of thyme, are known to act as skin sensitizers and allergens.⁵

Photoprotective activity

Recently, Sun et al. showed that UVB-induced skin damage was attenuated by treating hairless mice (HR-1) with T. vulgaris, as indicated by reduced matrix metalloproteinases and elevated collagen synthesis. In cultured normal human dermal fibroblasts, the investigators found that T. vulgaris blocked UVB-induced reactive oxygen species and lactate dehydrogenase, and dose-dependently yielded increases in glutathione, NAD(P)H: quinone oxidoreductase 1, and heme oxygenase-1. Further, the botanical significantly reduced UVB-induced phosphorylation of mitogen-activated protein kinases. The investigators concluded that T. vulgaris has potential for use in preventing skin damage caused by UV radiation–induced oxidative stress.⁶

Thyme also was demonstrated by Cornaghi et al. in 2016 to exert a protective effect on normal human skin explants obtained from seven young healthy women that were treated 1 hour before UVB irradiation.⁷

In 2015, Calò et al. evaluated the protective effects of a dry extract from T. vulgaris and its primary synthetic constituent thymol against UVA- and UVB-induced oxidative and genotoxic damage in the keratinocyte cell line NCTC 2544. Both thymol and T. vulgaris suppressed reactive oxygen species production in UVA- and UVB-treated cells, but lowered malondialdehyde synthesis only in cells treated with UVA.⁸

Antioxidant activity

In 2007, Wei and Shibamoto reported that thyme essential oil mixed with clove oil exhibited over a 90% inhibitory effect against the formation of malondialdehyde. They speculated that the presence of thymol and eugenol might account for the strong antioxidant activity displayed by the thyme/clove leaf combination.⁹ The investigators previously observed antioxidant activities exhibited by volatile extracts isolated from thyme (as well as various other herbs and spices) using aldehyde/carboxylic acid as well as conjugated diene assays.¹⁰ The antioxidant activity of thyme also was demonstrated by Miura et al. using the oil stability index method.¹¹

Antimicrobial activity

In 2011, Sienkiewicz et al. reported that the oil of T. vulgaris displayed potent activity against clinical bacterial strains of Staphylococcus, Enterococcus, Escherichia, and Pseudomonas genera. In addition, thyme essential oil exhibited efficacy against tested antibiotic-resistant strains of bacteria.¹² The following year, Sienkiewicz et al. assessed the antimicrobial activity of thyme essential oil against clinical multidrug-resistant strains of Staphylococcus, Enterococcus, Escherichia, and Pseudomonas, finding that it potently suppressed the growth of each.¹³

Potential cutaneous indications: atopic dermatitis, leishmaniasis, eczema, hair growth

In 2015, Seo and Jeong showed that lavender oil, thyme oil, and a blend of the two were all effective in reducing the symptoms of atopic dermatitis in mice. The researchers suggested that developing treatments with these oils for human patients with atopic dermatitis is warranted.¹⁴

Nilforoushzadeh et al. found in 2008 that herbal extracts of T. vulgaris and Achillea millefolium (yarrow), as well as propolis hydroalcoholic extracts, were effective in treating cutaneous leishmaniasis in mice and recommended the study of these extracts alone or in combination in human trials.¹⁵

A two-arm, randomized, double-blind, placebo-controlled trial conducted by Shimelis et al. in 2012 evaluated the efficacy of a 3% thyme essential oil antifungal cream and a 10% chamomile extract cream in the treatment of eczemalike lesions. Complete healing was achieved in 10 patients (66.5%) treated with the thyme cream, compared with four patients (28.5%) in the placebo group. Although no significant differences were observed between the active chamomile group and placebo, an appreciable number of subjects improved or healed. The investigators concluded that their findings from this small study suggest that, while more research is needed, a 3% thyme essential oil cream appears to be an inexpensive and readily available option to treat mild to moderate cutaneous conditions, including fungal infections, pityriasis alba, and eczema.¹⁶

In 2013, Rastegar et al. found that the combination of herbal extracts (including thyme) and platelet-rich plasma induced significant proliferation of human dermal papilla cells by regulating extracellular signal-regulated kinase (ERK) and Akt (protein kinase B). They concluded that their findings suggest the potential for developing combination therapies intended to improve hair growth.¹⁷

Insect repellent activity

In a 2016 study by Gutiérrez et al., the essential oil of T. vulgaris was found to be effective against Pediculus humanus capitis (head lice) adults and eggs. The researchers concluded that T. vulgaris achieves a strong knockdown and mortality rate in adult head lice and toxicity in the eggs after 21 minutes of application at a low concentration.¹⁸

In a small 1999 study by Barnard of the repellency to Aedes aegypti and Anopheles albimanus of various concentrations and combinations of five essential oils (Bourbon geranium, cedarwood, clove, peppermint, and thyme) applied to human skin, thyme and clove oils were found to be the most effective mosquito repellents. The author noted that thyme oil (as well as clove and peppermint oils) can irritate the skin and the odor of thyme and clove oils, at concentrations of 25%, or more were deemed unacceptable by the two participants in the study.¹⁹

Three years later, Choi et al. found that the essential oil of T. vulgaris also repelled adult mosquitoes (Culex pipiens pallens) on hairless mice and displayed potent repellent activity.²⁰

Melanoma

In 2005, Carrera et al. reported a case of long-term complete remission of cutaneous melanoma metastases in a 73-year-old white woman who consumed a dried thyme herbal tea and thyme topical applications in compresses.⁴ An association between thyme and melanoma has not been reported in the subsequent literature.

Conclusion

Thyme has a long history of culinary and medical uses. Its antimicrobial and antioxidant activity are well documented. While there is reason to consider the potential applications of thyme for dermatologic conditions, much more research is necessary to determine its viability for such purposes.

References

1. An Illustrated Guide to 101 Medicinal Herbs: Their History, Use, Recommended Dosages, and Cautions (Loveland, Colo.: Interweave Press, 1998, pp. 198-9).

2. J Ethnopharmacol. 2010 Aug 19;131(1):33-55.

3. J Food Sci. 2014 May;79(5):M903-10.

4. J Am Acad Dermatol. 2005 Apr;52(4):713-5.

5. Nat Neurosci. 2006 May;9(5):628-35.

6. J Cell Mol Med. 2016 Sep 19. doi: 10.1111/jcmm.12968. [Epub ahead of print]

7. Cells Tissues Organs. 2016;201(3):180-92.

8. Mutat Res Genet Toxicol Environ Mutagen. 2015 Sep;791:30-7.

9. Cutan Ocul Toxicol. 2007;26(3):227-33.

10. J Agric Food Chem. 2002 Aug 14;50(17):4947-52.

11. J Agric Food Chem. 2002 Mar 27;50(7):1845-51.

12. Med Chem. 2011 Nov;7(6):674-89.

13. Microb Drug Resist. 2012 Apr;18(2):137-48.

14. J Korean Acad Nurs. 2015 Jun;45(3):367-77.

15. J Vector Borne Dis. 2008 Dec;45(4):301-6.

16. Int J Dermatol. 2012 Jul;51(7):790-5.

17. J Cosmet Dermatol. 2013 Jun;12(2):116-22.

18. Parasitol Res. 2016 Feb;115(2):633-41.

19. J Med Entomol. 1999 Sep;36(5):625-9.

20. J Am Mosq Control Assoc. 2002 Dec;18(4):348-51.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever. Dr. Baumann also developed and owns the Baumann Skin Type Solution skin typing systems and related products.

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Potential cutaneous indications: atopic dermatitis, leishmaniasis, eczema, hair growth

Insect repellent activity

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Conclusion

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Potential cutaneous indications: atopic dermatitis, leishmaniasis, eczema, hair growth

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Shea butter

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Indigenous to Africa, Vitellaria paradoxa, better known as the shea or shi tree, is a member of the Sapotaceae family. It has long been used in traditional medicine in sub-Saharan West Africa (as far west as Mali) as well as parts of East Africa (as far east as Uganda and Ethiopia) for its anti-inflammatory and analgesic properties.^1,2

Some indications in traditional Nigerian medicine include nasal congestion, scabies, and ulcers.² In addition, anecdotal success in treating keloids has been reported in association with traditional African remedies, including shea butter and boa constrictor oil.³ Antioxidant activities have also been linked to V. paradoxa.⁴ Given such purported properties, it is not surprising that demand for shea kernels and butter has steadily increased in recent years for various purposes, including use as food (particularly as a cocoa butter additive in chocolate) and in medical and cosmetic products.^2,4 The use of shea butter in skin care is attributed to its hydrating qualities and reputed effectiveness in softening scars.³

Constituents

Shea butter contains fatty acids that have been shown to improve the skin barrier. These include palmitic, stearic, and linoleic acid. It also contains the fatty acids oleic and arachidic. Shea butter also has phenolic components that function as antioxidants.

Analysis of the phenolic constituents of shea kernels has demonstrated the presence of quercetin, trans-cinnamic acid, and eight catechins (gallic acid, catechin, epicatechin, epicatechin gallate, gallocatechin, epigallocatechin, gallocatechin gallate, and epigallocatechin gallate), many of which are also found in green tea. The concentration of these catechins in V. paradoxa varies by region in Africa. Gallic acid is considered the primary phenolic constituent, ranging from 27% to 70% of the total phenols identified in various areas of Africa.⁵ Triterpene alcohols are known to display various biological activities; the primary nonglyceride components of shea butter are believed to be triterpene alcohols (including alpha- and beta-amyrin, lupeol, and butyrospermol).²

Anti-inflammatory effects

In 2010, Akihisa et al. evaluated the inhibitory effects of four triterpene acetates and four triterpene cinnamates isolated from the kernel fat of V. paradoxa against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in mice. All of the tested compounds showed considerable anti-inflammatory activity (ID50 values ranged from 0.15 to 0.75 micromol/ear). Lupeol cinnamate displayed the greatest anti-inflammatory activity, on carrageenan-induced edema on rat hind paws. All eight substances also exhibited moderate inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) in Raji cells as a primary screening test for tumor promoter inhibitors. Using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter in a two-stage carcinogenesis model in mice, the investigators also found that lupeol cinnamate inhibited skin tumor promotion. They concluded that the triterpenes and triterpene esters found in shea nuts and shea butter are significant anti-inflammatory and antitumor-promoting agents.²

The next year, Akihisa et al. determined the triacylglycerol and triterpene ester fraction composition of the kernel fats of the shea tree from 36 samples from Cote d’Ivoire, Ghana, Nigeria, Cameroon, Chad, Sudan, and Uganda. There were no significant differences in the composition of the triterpene ester fractions between West African and East African plants. Generally, though, West African shea kernel fats contained higher levels of high-melting triacylglycerols (e.g., stearic-oleic-stearic) and triterpene esters.⁶

Also that year, Olaitan et al. found that shea butter (as well as boa constrictor oil) was effective in suppressing the in vitro growth of normal and keloid fibroblasts.³

In 2012, Verma et al. used the lipopolysaccharide (LPS)-induced murine macrophage cell line J774 to investigate the anti-inflammatory properties of the methanolic extract of shea butter. They found that shea butter extract dose-dependently reduced, to a significant degree, the levels of nitric oxide, tumor necrosis factor (TNF)–alpha, as well as interleukin (IL)-1beta and IL-12 in the culture supernatants. In addition, the botanical extract suppressed IkappaB phosphorylation and NF-kappaB nuclear translocation as well as the expression of pro-inflammatory enzymes, inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX)-2. The investigators attributed the anti-inflammatory activity of the extract to its inhibitory impact on LPS-induced iNOS, COX-2, TNF-alpha, IL-1beta, and IL-12 mRNA expression.¹

In 2014, Honfo et al. conducted a literature review indicating that shea pulp is laden with vitamin C and the kernels contain copious fat (butter), which is used in food, drugs, and cosmetics.⁴

Notably, shea butter is also an ingredient in the topical nonsteroidal anti-inflammatory drug (NSAID) atopiclair, which has shown efficacy in alleviating pruritus in adults with mild to-moderate atopic dermatitis.⁷

Conclusion

Shea butter has long been incorporated into traditional medical practice in West and East Africa based on observed anti-inflammatory and analgesic characteristics. Such uses are compelling and often the basis for systematic scientific investigation. That said, there remains a dearth of experimental and clinical research on the potential cutaneous benefits of topically applied shea butter. Current data and traditional applications provide ample reason for continued research into this popular botanical agent.

References

1. J Complement Integr Med. 2012;9:Article 4.

2. J Oleo Sci. 2010;59[6]:273-80)

3. Wounds. 2011;23[4]:97-106.

4. Crit Rev Food Sci Nutr. 2014;54[5]:673-86.

5. J Agric Food Chem. 2003;51[21]:6268-73.

6. J Oleo Sci. 2011;60[8]:385-91.

7. J Drugs Dermatol. 2009 Jun;8[6]:537-9.

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1. J Complement Integr Med. 2012;9:Article 4.

2. J Oleo Sci. 2010;59[6]:273-80)

3. Wounds. 2011;23[4]:97-106.

4. Crit Rev Food Sci Nutr. 2014;54[5]:673-86.

5. J Agric Food Chem. 2003;51[21]:6268-73.

6. J Oleo Sci. 2011;60[8]:385-91.

7. J Drugs Dermatol. 2009 Jun;8[6]:537-9.

Constituents

Anti-inflammatory effects

Conclusion

References

1. J Complement Integr Med. 2012;9:Article 4.

2. J Oleo Sci. 2010;59[6]:273-80)

3. Wounds. 2011;23[4]:97-106.

4. Crit Rev Food Sci Nutr. 2014;54[5]:673-86.

5. J Agric Food Chem. 2003;51[21]:6268-73.

6. J Oleo Sci. 2011;60[8]:385-91.

7. J Drugs Dermatol. 2009 Jun;8[6]:537-9.

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Update on argan oil

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• Used traditionally in Northwest Africa for its cosmetic, bactericidal, and fungicidal activity.

• Rich in vitamin E, oleic acid, and linoleic acid, which are believed to contribute to the perceived cutaneous benefits of this vegetable oil.

• Reputed to impart antiacne, antisebum, antiaging, moisturizing, and wound-healing activity, but clinical evidence is sparse.

• In a small study, the nightly topical application of argan oil resulted in a moisturizing effect, and in statistically significant decreases in transepidermal water loss and increases in the water content of the epidermis.

For more than 800 years, native Moroccans and explorers in the region have cited the health benefits of the topical use or consumption of argan oil.¹ The oil, derived from the fruit of Argania spinosa, is a slow-growing tree native to the arid climate of Southwestern Morocco^2-4 as well as the Algerian province of Tindouf in the Western Mediterranean area.⁵ For many years, it was primarily the populations of the Essaouira and Souss-Massa-Draa regions of Morocco that benefited from the production and use of argan oil.⁶ Largely through the efforts of the Moroccan government, as well as cooperating nongovernmental organizations and private entities, argan oil is now also a well-established ingredient on the edible oil as well as cosmetic oil markets throughout the world.⁶

Traditionally, the vegetable oil has been prescribed for reputed cosmetic, bactericidal, and fungicidal properties and as a treatment for infertility and heart disease.^3,4 In fact, investigations related to the cardiovascular benefits of virgin argan oil consumption have suggested antiatherogenic, cholesterol-lowering, antiproliferative, and antioxidant benefits.^7-11

The vitamin E–rich oil has a reputation for imparting antiaging, hydrating, and antioxidant activity to the skin and ameliorating conditions such as acne, eczema, psoriasis, wrinkles, and xerosis,¹² and, in fact, has been used to treat these conditions as well as dry hair,^3,13 hair loss, skin inflammation, and joint pain.³This column will focus on the topical uses of this botanical that has been dubbed “liquid gold.”¹²

Chemistry

Oleic acid, an omega-9 monounsaturated fatty acid, is abundant in argan oil (43%-49%) and has been found to act as a penetration enhancer by disturbing the skin barrier.^14,15Linoleic acid, an omega-6 polyunsaturated fatty acid, found in concentrations of 29%-36% in the oil, is integral in the biosynthesis of inflammatory prostaglandins through the arachidonic acid pathway.^4,16 The presence of linoleic acid may help prevent or mitigate inflammation. Linoleic acid is also a component of ceramide 1 linoleate, which is diminished in dry skin. Topical application of linoleic acid can raise ceramide 1 linoleate levels in the skin, thus reducing xerosis.¹⁷ Argan oil also contains the saturated fatty acids palmitic acid (11%-15%) and stearic acid (4%-7%).²

Though argan oil is mainly composed of unsaturated fatty acids (80%),^1,18,19 the unsaponifiable fraction (1%) is replete with antioxidants, including sterols, saponins, and polyphenols.^4,19 The polyphenolic constituents, primarily gamma-tocopherol, which is considered the most efficient among the tocopherols at scavenging free radicals, are thought to account for the antioxidant effects of argan oil.^1,2,18,20,21

Topical uses

Unroasted kernels are used to produce cosmetic-grade argan oil, which is used in moisturizing creams, body lotions, and shampoos.² Although argan oil contains components that have antioxidant and anti-inflammatory features and there are many patents on the use of argan oil in skin care, there is a dearth of published research studies looking at the effect of argan oil–containing skin care products on aging, inflamed, or dry skin. A study by Dobrev evaluated the efficacy of a sebum control cream composed of saw palmetto extract, sesame seeds, and argan oil applied twice daily to the face over a period of 4 weeks in 20 healthy volunteers, 16 with oily skin and 4 with combination skin. All volunteers tolerated the product. A visible sebum-regulating or antisebum efficacy was observed in 95% of the subjects. Clinical evaluation scores and casual sebum levels decreased significantly after 1 month of treatment. Dobrev concluded that this argan oil-containing formulation was efficacious in lessening the greasiness and improving the appearance of oily facial skin.²²

By Consultaplantas/Wikimedia Commons/CC BY-SA 4.0

Shown is Argania spinosa fruit, the source of argan oil.

In 2014, Tichota et al. created a topical argan oil nanostructured lipid carrier formulation to enhance skin hydration and tested it in a single-blind controlled trial with healthy volunteers over a 1-month period. The investigators observed that nanostructured lipid carrier entrapment in the hydrogel formulation did not have an impact on colloidal size or occlusion, and, clinically, skin hydration was improved in the participants, suggesting the effectiveness of argan oil as a liquid lipid for this indication.²³

Early in 2015, Boucetta et al. reported on their study of the effects on skin elasticity of the daily application or consumption of argan oil in 60 postmenopausal women. During a 60-day period, the treatment group of 30 subjects consumed dietary argan oil; the 30 members in the control group received olive oil. Both groups also applied topical argan oil to the left volar forearm. Skin parameters, including gross skin elasticity, net elasticity, and biologic elasticity, improved significantly with both oral and topical treatments. The researchers concluded that argan oil use confers an antiaging effect to the skin through enhanced elasticity.²⁴ Boucetta and another team previously showed that daily consumption or topical application of argan oil in postmenopausal women yielded significant reductions in transepidermal water loss and significant increases in epidermal water content, suggesting that the botanical agent ameliorates skin hydration by reviving barrier function and preserving the water-holding capacity.²⁵ The same team also demonstrated in 30 healthy postmenopausal women that the nightly topical application of argan oil over a 2-month period yielded a moisturizing effect, with statistically significant reductions in transepidermal water loss and statistically significant increases in the water content of the epidermis observed.²⁶

As a cosmetic agent, argan oil, which is popular in France, Japan, and North America, is touted for hydrating and revitalizing the skin, treating acne, and imparting shine to the hair. The therapeutic activities of topical argan oil are reputed to be antiacne, antisebum, antiaging, moisturizing, and wound healing, but such claims are based on traditional uses with only a small body of supportive clinical evidence.^2,27

Generally, argan oil prices are as high as $40/100 mL in the European, Japanese, and American markets.²⁷Topical argan oil has been characterized as having a brief shelf-life of approximately 3-4 months.^2,28A 2014 report on a 1-year study of the oxidative stability of cosmetic argan oil by Gharby et al. found that argan oil quality remains satisfactory when stored at 25° C and protected from sunlight, but storage should not exceed 6 months to meet industrial standards. A rapid loss of quality was seen when argan oil was stored at 40° C.²⁹

Conclusion

Although clinical research data on argan oil are limited, its traditional uses and inclusion in novel cosmetic products suggest that further study is warranted. Randomized controlled trials are needed to elucidate cutaneous benefits, if any, from this rare botanical.

1. J Pharm Pharmacol. 2010 Dec;62(12):1669-75.

2. Altern Med Rev. 2011 Sep;16(3):275-9.

3. J Ethnopharmacol. 1999 Oct;67(1):7-14.

4. Pharmacol Res. 2006 Jul;54(1):1-5.

5. Nutr Rev. 2012 May;70(5):266-79.

6. Eur J Lipid Sci Technol. 2014 Oct;116(10):1316-21.

7. Ann Nutr Metab. 2005 May-Jun;49(3):196-201.

8. Nutr Metab Cardiovasc Dis. 2005 Oct;15(5):352-60.

9. Evid Based Complement Alternat Med. 2006 Sep;3(3):317-27.

10. Cancer Invest. 2006 Oct;24(6):588-92.

11. Cancer Detect Prev. 2007;31(1):64-9.

12. “Liquid Gold in Morocco,” by Amy Larocca, The New York Times, Nov. 18, 2007.

13. Phytomedicine. 2010 Feb;17(2):157-60.

14. J Control Release. 1995;37(3):299-306.

15. Thermochimica Acta. 1997 Jun;293:77-85.

16. Prostaglandins Leukot Essent Fatty Acids. 1995 Jun;52(6):387-91.

17. Int J Cosmet Sci. 1996 Feb;18(1):1-12.

18. Crit Rev Food Sci Nutr. 2010 May;50(5):473-7.

19. Eur J Cancer Prev. 2003 Feb;12(1):67-75.

20. Fitoterapia. 2008 Jul;79(5):337-44.

21. Am J Clin Nutr. 2001 Dec;74(6):714-22.

22. J Cosmet Dermatol. 2007;6(2):113-8.

23. Int J Nanomedicine. 2014 Aug 11;9:3855-64.

24. Clin Interv Aging. 2015 Jan 30;10:339-49.

25. Prz Menopauzalny. 2014 Oct;13(5):280-8.

26. Skin Res Technol. 2013;19:356-7.

27. Inflamm Allergy Drug Targets. 2014;13(3):168-76.

28. Nat Prod Commun. 2010 Nov;5(11):1799-802.

29. J Cosmet Sci. 2014 Mar-Apr;65(2):81-7.

Dr. Baumann is the CEO of Baumann Cosmetic & Research Institute in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. She is the author of “Cosmetic Dermatology: Principles and Practice” (New York: McGraw Hill, 2002), and a book for consumers, “The Skin Type Solution,” (New York: Bantam Dell, 2006). Her latest book, “Cosmeceuticals and Cosmetic Ingredients” (McGraw Hill) was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever. She also develops and owns the Baumann Skin Type Solution skin typing solutions and related products.

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By Consultaplantas/Wikimedia Commons/CC BY-SA 4.0

Shown is Argania spinosa fruit, the source of argan oil.

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Shown is Argania spinosa fruit, the source of argan oil.

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Update on resveratrol

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1. Toxicol Appl Pharmacol. 2003 Jan 1;186(1):28-37.

• Found abundantly in nature, this polyphenolic phytoalexin is believed to exhibit a wide range of biologic activity.

• Potent antioxidant, anti-inflammatory, and antiproliferative properties.

• Highly studied polyphenolic substance also considered a chemopreventive agent against skin cancer.

• In small studies, has contributed to antiaging, antiacne, antierythema, and skin-lightening results.

Resveratrol (trans-3,5,4’-trihydroxystilbene), a polyphenolic phytoalexin synthesized in nearly 70 plant species, is found to be particularly abundant in Vitis vinifera (grape vine) and its derivatives (e.g., red wine, purple grape juice), various berries, peanuts, jackfruit, pomegranate, eucalyptus, the roots of Polygonum cuspidatum (Japanese knotweed, which is used in traditional Chinese and Japanese medicine to treat dermatitis, among other conditions)¹, Scots pine, spruce, corn lily, gnetum, and butterfly orchid.^2-6 Several studies have demonstrated that resveratrol possesses potent antioxidant, anticarcinogenic, anti-inflammatory, as well as antimicrobial characteristics.^7-11 Specifically, in vitro and in vivo studies have shown that resveratrol exerts chemopreventive and antiproliferative activity against various cancers, including skin cancer, by suppressing cellular events associated with tumor initiation, promotion, and progression, and triggering apoptosis in such tumor cells.^12-14 It also is reputed to impart antiaging benefits.¹⁵ This column will focus on recent research findings pertaining to effects on the skin as well as topical uses of this botanical agent, the main source of which, V. vinifera, has been used since antiquity.

Resveratrol was first identified from the roots of Veratrum grandiflorum (white hellebore) in 1940,^16-19 but research on the compound did not take root until after a 1997 report in Science suggested chemopreventive properties. In that study, purified resveratrol was found to exhibit major inhibitory activity against cancer initiation, promotion, and progression.²⁰ Since then, copious research on this botanical compound has yielded a reputation as a strong antioxidant, anti-inflammatory, and antiproliferative agent.^7,21,22 Most importantly, resveratrol is considered to act as a chemopreventive agent against skin cancer and antiproliferative influence on oral squamous, breast, colon, and prostate cancer cells.^12,14 It is also one of the most studied polyphenolic compounds.

Skin cancer and photoprotection

In 2012, Osmond et al. conducted in vitro and in vivo experiments to assess the potential of resveratrol as a chemotherapy adjunct for melanoma treatment. Resveratrol significantly reduced melanoma cell viability in both melanoma cell lines tested, and selectively spared cells in the nonmalignant fibroblast lines, compared with its cytotoxic impact on melanoma cells. Further, cytotoxicity to malignant cells was greatly enhanced by 72 hours of treatment with resveratrol and temozolomide, compared with temozolomide treatment alone. No significant differences were seen in vivo. The researchers concluded that the in vitro antitumor activity of resveratrol suggested its potential as a therapeutic agent in melanoma management.²³

Resveratrol has been shown to protect against UVB-mediated cutaneous damage in SKH-1 hairless mice. Afaq et al. demonstrated that UVB-induced skin edema was significantly suppressed by the topical application of resveratrol to SKH-1 hairless mice.⁷

Vitis viniferam, grapes and grape vine, from which resveratol is derived.

In a different study by the same team, topically applied resveratrol significantly inhibited UVB-mediated increases in bifold skin thickness and edema and greatly diminished UVB-induced lipid peroxidation, cyclo-oxygenase and ornithine decarboxylase (ODC) activities, as well as protein expression of the ODC enzyme in SKH-1 hairless mice.²⁴ In an experiment by some of the same researchers, resveratrol was topically applied to SKH-1 hairless mice 30 minutes before exposure to UVB; 24 hours later, significant decreases were observed in bifold skin thickness, hyperplasia, and leukocyte infiltration. Critical cell cycle regulatory proteins, the target of the investigation, were substantially down-regulated because of the resveratrol. The investigators concluded that resveratrol might have the potential to play a significant role in preventing UVB-mediated photodamage and carcinogenesis.²⁵

More recently, in 2015, Sirerol et al. found that the topical treatment with pterostilbene, a natural dimethoxy analog of resveratrol, effectively shielded SKH-1 hairless mice from UVB-induced photodamage and carcinogenesis.²⁶

Interestingly, recent in vitro studies by Sticozzi and colleagues have shown that topical resveratrol dose-dependently protected human keratinocytes from cigarette smoke–induced reduction of scavenger receptor B1 protein expression²⁷ and can lower cigarette smoke–induced reactive oxygen species and carbonyl formation in human keratinocytes.²⁸

Antiaging activity

In 2010, Giardina et al. performed an in vitro study to evaluate the tonic-trophic characteristics of resveratrol alone and resveratrol plus N-acetyl-cysteine on cultured skin fibroblasts. Both formulations dose-dependently increased cell proliferation and inhibition of collagenase activity.²⁹

In 2012, Wu et al. investigated the protective effects of resveratrate, a stable derivative of resveratrol, against damage to human skin caused by repetitive solar simulator UV radiation (ssUVR) in 15 healthy human volunteers. Six sites on nonexposed dorsal skin of each participant were assessed, with four sites exposed to ssUVR and the remaining sites serving as positive control (ssUVR only) and baseline control (no treatment or exposure). The researchers noted minimal erythema on areas treated with resveratrate and the resveratrol derivative significantly inhibited sunburn cell formation. They concluded that resveratrate protects the skin against sunburn and suntan caused by repetitive ssUVR.⁴

Also that year, Buonocore et al. conducted a placebo-controlled, double-blind study in 50 subjects that revealed the antiaging efficacy of a dietary nutraceutical blend of resveratrol and procyanidin. Specifically, skin moisturization and elasticity improved while wrinkle depth and skin roughness lessened after 60 days of treatment.³⁰

In a 2013 in vitro study of the skin permeation kinetics of polyphenols using diffusion cells via ex vivo pig skin and a cellulose membrane, Zillich et al. showed that several polyphenols, including resveratrol, epigallocatechin gallate, quercetin, rutin, and protocatechuic acid formulated in oil-in-water emulsions could permeate the stratum corneum and were identified in the epidermis and dermis. The team concluded that their findings validate the use of polyphenols as active ingredients in antiaging products.³¹

In 2014, Farris et al. found that the topical application of resveratrol in a proprietary blend (1% resveratrol, 0.5% baicalin, 1% vitamin E) yielded a statistically significant amelioration of fine lines and wrinkles, hyperpigmentation, radiance, as well as skin roughness, firmness, elasticity, and laxity in a small study over 12 weeks.³²

Skin lightening

Resveratrol has also been used as a promising topical treatment for hyperpigmentation disorders.³³ The compound has been shown to work synergistically with 4-n-butylresorcinol (a derivative of resorcinol, one of the main phenols found in argan oil) to reduce tyrosinase levels and significantly diminish melanin synthesis, more effectively than either compound alone.³⁴ In 2012, Franco et al. observed that resveratrol can inhibit tyrosinase but it does not sufficiently suppress melanin production to justify its use as a lone skin-whitening agent in pharmaceutical formulations, but warrants attention as a coadjuvant for treating hyperpigmentation.³⁵ The skin-lightening capacity of resveratrol supported by a 2013 study in which 52 medicinal plants grown in Korea were tested for human tyrosinase activity and the dried stems of the grape tree V. vinifera were found to potently suppress human tyrosinase, and more effectively than arbutin.³⁶ It is worth noting that resveratrol, through its antioxidant activity and possible inhibitory effect on cytochrome P450 2E1 expression, has been shown to protect mouse primary hepatocytes from hydroquinone-induced cytotoxicity.³⁷ Also, J.M. Galgut and S.A. Ali, noted the gathering of pigment cells and resultant skin lightening from the effects of topical ethanolic extract of Arachis hypogaea (peanuts, which contain half the resveratrol of red wine) on the tail melanophores of tadpole Bufo melanostictus, concluding that resveratrol merits attention for potential clinical use as a nontoxic melanolytic agent to treat hyperpigmentation.^38,34

Acne

Resveratrol is considered an emerging agent in the topical armamentarium for treating acne.³⁹ In a single-blind pilot study in 2011, Fabbrocini et al. investigated the potential therapeutic impact of resveratrol on 20 patients with acne. A resveratrol-containing hydrogel was applied daily on the right side of the face for 60 days, with the left side receiving the hydrogel vehicle as control. No adverse effects were reported and all patients were satisfied with the treatment. Researchers reported a 53.75 % mean reduction in the Global Acne Grading System score on the resveratrol-treated sides and a 6.10 % decrease on the control sides. Histologic analysis revealed a statistically significant reduction of lesions in areas treated with resveratrol (66.7 % mean reduction in the average area of microcomedones on the resveratrol-treated sides vs. 9.7% reduction on the control sides).⁴⁰

A 2015 comprehensive literature review of randomized clinical trials and controlled trials by Dall’oglio et al. found that cosmetics with antimicrobial and anti-inflammatory ingredients, including resveratrol, may accelerate acne resolution.⁴¹

Significantly, resveratrol is one of the novel acne treatments considered to have little potential for susceptibility to antibiotic resistance to Propionibacterium acnes.⁴²

Erythema

In a small 2013 study by Ferzli et al., 16 subjects with erythema applied a formulation containing resveratrol, green tea polyphenols, and caffeine twice daily to the whole face. Clinical photographs and spectrally enhanced images taken before treatment and every 2 weeks through 3 months were assessed. The investigators reported that improvement was seen in 16 of 16 clinical images and 13 of 16 spectrally enhanced images. Erythema reduction was observable by 6 weeks of treatment, and no adverse effects were observed.⁴³

Conclusion

Resveratrol is emerging as a compound with the potential to deliver significant health benefits, particularly in terms of photoprotective, cancer preventive, and cardioprotective activity. While there are 2 strong decades of research, more is necessary to elucidate the full potential of resveratrol as a first-line dermatologic therapy. Preclinical data do support the use of resveratrol in various product types (e.g., emollients, patches, sunscreens, and additional skin care products) intended to prevent skin cancer or to prevent or treat other conditions caused or exacerbated by solar exposure, such as photoaging. I look forward to seeing clinical evidence of the efficacy of topically applied resveratrol.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever. She also developed and owns the Baumann Skin Type Solution skin-typing systems and related products.

References

2. Science. 1997 Jan 10;275(5297):218-20.

3. Cancer Res. 2001 Feb 15;61(4):1604-10.

4. J Eur Acad Dermatol Venereol. 2013 Mar;27(3):345-50.

5. Photochem Photobiol. 2008 Mar-Apr;84(2):415-21.

6. Dose Response. 2010 Mar 18;8(4):478-500.

7. Toxicol Appl Pharmacol. 2003 Jan 1;186(1):28-37.

8. Neoplasia. 2003 Jan-Feb;5(1):74-82.

9. An Illustrated Guide to 101 Medicinal Herbs: Their History, Use, Recommended Dosages, and Cautions (Loveland, Colo.: Interweave Press, 1998, pp. 108-9.)

10. Medical Herbalism: The Science and Practice of Herbal Medicine. (Rochester, Vt.: Healing Arts Press, 2003, pp. 99-100).

11. Eur J Pharm Sci. 2015 Oct 12;78:204-13.

12. Pancreas. 2002 Nov;25(4):e71-6.

13. Toxicol Appl Pharmacol. 2007 Nov 1;224(3):274-83.

14. J Biol Chem. 2003 Oct 17;278(42):41482-90.

15. J Drugs Dermatol. 2014 Dec;13(12):1467-72.

16. Fitoterapia. 2013 Apr;86:84-91.

17. Ann N Y Acad Sci. 2011 Jan;1215:60-71.

18. Recent Pat Cardiovasc Drug Discov. 2007 Jun;2(2):133-8.

19. Anticancer Res. 2004 Sep-Oct;24(5A):2783-840.

20. Science. 1997 Jan 10;275(5297):218-20.

21. Biochem Pharmacol. 2002 Jan 15:63(2):99-104.

22. Biomed Pap Med Fac univ Palacky Olomouc Czech Repub. 2003 Dec;147(2):137-45.

23. J Surg Res. 2012 Jan;172(1):109-15.

24. Front Biosci. 2002 Apr 1;7:d784-92.

25. Oncogene. 2004 Jul 1;23(30):5151-60.

26. Free Radic Biol Med. 2015 Aug;85:1-11.

27. Free Radic Biol Med. 2014 Apr;69:50-7.

28. Food Funct. 2014 Sep;5(9):2348-56.

29. Minerva Ginecol. 2010 Jun;62(3):195-201.

30. Clin Cosmet Investig Dermatol. 2012;5:159-65.

31. Int J Cosmet Sci. 2013 Oct;35(5):491-501.

32. J Drugs Dermatol. 2014 Dec;13(12):1467-72.

33. Semin Cutan Med Surg. 2012 Jun;31(2):133-9.

34. Pharmazie. 2012 Jun;67(6):542-6.

35. Molecules. 2012 Oct 9;17(10):11816-25.

36. Evid Based Complement Alternat Med. 2013;2013:645257.

37. Int J Environ Res Public Health. 2012 Sep 19;9(9):3354-64.

38. J Recept Signal Transduct Res. 2011 Oct;31(5):374-80.

39. Am J Clin Dermatol. 2012 Dec 1;13(6):357-64.

40. Am J Clin Dermatol. 2011 Apr 1;12(2):133-41.

41. G Ital Dermatol Venereol. 2015 Feb;150(1):1-11.

42. Expert Rev Anti Infect Ther. 2015 Jul;13(7):883-96.

43. J Drugs Dermatol. 2013 Jul 1;12(7):770-4.

References

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1. Toxicol Appl Pharmacol. 2003 Jan 1;186(1):28-37.

Author and Disclosure Information

• Found abundantly in nature, this polyphenolic phytoalexin is believed to exhibit a wide range of biologic activity.

• Potent antioxidant, anti-inflammatory, and antiproliferative properties.

• Highly studied polyphenolic substance also considered a chemopreventive agent against skin cancer.

• In small studies, has contributed to antiaging, antiacne, antierythema, and skin-lightening results.

Skin cancer and photoprotection

Antiaging activity

Skin lightening

Acne

Significantly, resveratrol is one of the novel acne treatments considered to have little potential for susceptibility to antibiotic resistance to Propionibacterium acnes.⁴²

Erythema

Conclusion

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever. She also developed and owns the Baumann Skin Type Solution skin-typing systems and related products.

References

2. Science. 1997 Jan 10;275(5297):218-20.

3. Cancer Res. 2001 Feb 15;61(4):1604-10.

4. J Eur Acad Dermatol Venereol. 2013 Mar;27(3):345-50.

5. Photochem Photobiol. 2008 Mar-Apr;84(2):415-21.

6. Dose Response. 2010 Mar 18;8(4):478-500.

7. Toxicol Appl Pharmacol. 2003 Jan 1;186(1):28-37.

8. Neoplasia. 2003 Jan-Feb;5(1):74-82.

9. An Illustrated Guide to 101 Medicinal Herbs: Their History, Use, Recommended Dosages, and Cautions (Loveland, Colo.: Interweave Press, 1998, pp. 108-9.)

10. Medical Herbalism: The Science and Practice of Herbal Medicine. (Rochester, Vt.: Healing Arts Press, 2003, pp. 99-100).

11. Eur J Pharm Sci. 2015 Oct 12;78:204-13.

12. Pancreas. 2002 Nov;25(4):e71-6.

13. Toxicol Appl Pharmacol. 2007 Nov 1;224(3):274-83.

14. J Biol Chem. 2003 Oct 17;278(42):41482-90.

15. J Drugs Dermatol. 2014 Dec;13(12):1467-72.

16. Fitoterapia. 2013 Apr;86:84-91.

17. Ann N Y Acad Sci. 2011 Jan;1215:60-71.

18. Recent Pat Cardiovasc Drug Discov. 2007 Jun;2(2):133-8.

19. Anticancer Res. 2004 Sep-Oct;24(5A):2783-840.

20. Science. 1997 Jan 10;275(5297):218-20.

21. Biochem Pharmacol. 2002 Jan 15:63(2):99-104.

22. Biomed Pap Med Fac univ Palacky Olomouc Czech Repub. 2003 Dec;147(2):137-45.

23. J Surg Res. 2012 Jan;172(1):109-15.

24. Front Biosci. 2002 Apr 1;7:d784-92.

25. Oncogene. 2004 Jul 1;23(30):5151-60.

26. Free Radic Biol Med. 2015 Aug;85:1-11.

27. Free Radic Biol Med. 2014 Apr;69:50-7.

28. Food Funct. 2014 Sep;5(9):2348-56.

29. Minerva Ginecol. 2010 Jun;62(3):195-201.

30. Clin Cosmet Investig Dermatol. 2012;5:159-65.

31. Int J Cosmet Sci. 2013 Oct;35(5):491-501.

32. J Drugs Dermatol. 2014 Dec;13(12):1467-72.

33. Semin Cutan Med Surg. 2012 Jun;31(2):133-9.

34. Pharmazie. 2012 Jun;67(6):542-6.

35. Molecules. 2012 Oct 9;17(10):11816-25.

36. Evid Based Complement Alternat Med. 2013;2013:645257.

37. Int J Environ Res Public Health. 2012 Sep 19;9(9):3354-64.

38. J Recept Signal Transduct Res. 2011 Oct;31(5):374-80.

39. Am J Clin Dermatol. 2012 Dec 1;13(6):357-64.

40. Am J Clin Dermatol. 2011 Apr 1;12(2):133-41.

41. G Ital Dermatol Venereol. 2015 Feb;150(1):1-11.

42. Expert Rev Anti Infect Ther. 2015 Jul;13(7):883-96.

43. J Drugs Dermatol. 2013 Jul 1;12(7):770-4.

• Found abundantly in nature, this polyphenolic phytoalexin is believed to exhibit a wide range of biologic activity.

• Potent antioxidant, anti-inflammatory, and antiproliferative properties.

• Highly studied polyphenolic substance also considered a chemopreventive agent against skin cancer.

• In small studies, has contributed to antiaging, antiacne, antierythema, and skin-lightening results.

Skin cancer and photoprotection

Antiaging activity

Skin lightening

Acne

Significantly, resveratrol is one of the novel acne treatments considered to have little potential for susceptibility to antibiotic resistance to Propionibacterium acnes.⁴²

Erythema

Conclusion

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever. She also developed and owns the Baumann Skin Type Solution skin-typing systems and related products.

References

1. Toxicol Appl Pharmacol. 2003 Jan 1;186(1):28-37.

2. Science. 1997 Jan 10;275(5297):218-20.

3. Cancer Res. 2001 Feb 15;61(4):1604-10.

4. J Eur Acad Dermatol Venereol. 2013 Mar;27(3):345-50.

5. Photochem Photobiol. 2008 Mar-Apr;84(2):415-21.

6. Dose Response. 2010 Mar 18;8(4):478-500.

7. Toxicol Appl Pharmacol. 2003 Jan 1;186(1):28-37.

8. Neoplasia. 2003 Jan-Feb;5(1):74-82.

9. An Illustrated Guide to 101 Medicinal Herbs: Their History, Use, Recommended Dosages, and Cautions (Loveland, Colo.: Interweave Press, 1998, pp. 108-9.)

10. Medical Herbalism: The Science and Practice of Herbal Medicine. (Rochester, Vt.: Healing Arts Press, 2003, pp. 99-100).

11. Eur J Pharm Sci. 2015 Oct 12;78:204-13.

12. Pancreas. 2002 Nov;25(4):e71-6.

13. Toxicol Appl Pharmacol. 2007 Nov 1;224(3):274-83.

14. J Biol Chem. 2003 Oct 17;278(42):41482-90.

15. J Drugs Dermatol. 2014 Dec;13(12):1467-72.

16. Fitoterapia. 2013 Apr;86:84-91.

17. Ann N Y Acad Sci. 2011 Jan;1215:60-71.

18. Recent Pat Cardiovasc Drug Discov. 2007 Jun;2(2):133-8.

19. Anticancer Res. 2004 Sep-Oct;24(5A):2783-840.

20. Science. 1997 Jan 10;275(5297):218-20.

21. Biochem Pharmacol. 2002 Jan 15:63(2):99-104.

22. Biomed Pap Med Fac univ Palacky Olomouc Czech Repub. 2003 Dec;147(2):137-45.

23. J Surg Res. 2012 Jan;172(1):109-15.

24. Front Biosci. 2002 Apr 1;7:d784-92.

25. Oncogene. 2004 Jul 1;23(30):5151-60.

26. Free Radic Biol Med. 2015 Aug;85:1-11.

27. Free Radic Biol Med. 2014 Apr;69:50-7.

28. Food Funct. 2014 Sep;5(9):2348-56.

29. Minerva Ginecol. 2010 Jun;62(3):195-201.

30. Clin Cosmet Investig Dermatol. 2012;5:159-65.

31. Int J Cosmet Sci. 2013 Oct;35(5):491-501.

32. J Drugs Dermatol. 2014 Dec;13(12):1467-72.

33. Semin Cutan Med Surg. 2012 Jun;31(2):133-9.

34. Pharmazie. 2012 Jun;67(6):542-6.

35. Molecules. 2012 Oct 9;17(10):11816-25.

36. Evid Based Complement Alternat Med. 2013;2013:645257.

37. Int J Environ Res Public Health. 2012 Sep 19;9(9):3354-64.

38. J Recept Signal Transduct Res. 2011 Oct;31(5):374-80.

39. Am J Clin Dermatol. 2012 Dec 1;13(6):357-64.

40. Am J Clin Dermatol. 2011 Apr 1;12(2):133-41.

41. G Ital Dermatol Venereol. 2015 Feb;150(1):1-11.

42. Expert Rev Anti Infect Ther. 2015 Jul;13(7):883-96.

43. J Drugs Dermatol. 2013 Jul 1;12(7):770-4.

References

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Update on vitamin E

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Update on vitamin E

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1. J Mol Med (Berl). 1995 Jan;73(1):7-17.

Available in the diet through fresh vegetables (particularly green leafy vegetables), vegetable oils, grains, nuts, seeds, corn, soy, whole wheat flour, margarine, and in some meat and dairy products, vitamin E, or tocopherol, is the primary lipid-soluble antioxidant found in human skin (via sebum), membranes, plasma, and tissues that protects cells from oxidative stress.^1-4Vitamin E is often used to treat minor burns, surgical scars, and other wounds, although the Food and Drug Administration has not approved its use for skin conditions.

In 1938, Karrer, Fritzsche, Ringier, and Salomon became the first to synthesize alpha-tocopherol,^5,6 the main biologically active form of vitamin E.⁷ In the 1940s, vitamin E was labeled a “chain-breaking” antioxidant for its role in hindering the chain reaction induced by free radicals, and it is known to protect cutaneous cell membranes from peroxidation.⁸ Most topical formulations contain synthetic laboratory-made alpha-tocopherol or one of its many esters or ethers. As an ingredient in skin care agents, significant evidence has been amassed to suggest that topically applied vitamin E confers photoprotective activity against erythema, edema, sun burn cell formation, and other indicators of acute UV-induced damage as well as responses to chronic UVA and UVB exposure, including skin wrinkling and skin cancer.^2,9-14This column will focus on the topical applications of vitamin E.

Topical uses and findings

The lipophilic nature of vitamin E makes it suitable for topical application and percutaneous absorption through the skin.^9,15 Vitamin E is generally used in 1%-5% concentrations alpha-tocopherol or tocopherol acetate in over-the-counter products.¹⁶ When topically applied, vitamin E has been shown to hydrate the stratum corneum (SC) and improve water-binding capacity.¹⁶ It is also considered an effective ingredient for imparting skin protection and treating atopic dermatitis (AD).²

In 2005, Ekanayake-Mudiyanselage et al. studied whether one application of an alpha-tocopherol–enriched rinse-off product could effectively lead to deposition of alpha-tocopherol on the SC in 13 volunteers. The researchers found that the alpha-tocopherol product raised alpha-tocopherol levels in surface lipids, which remained consistent for at least 24 hours, whereas such levels were reduced in the alpha-tocopherol–free vehicle control group. The alpha-tocopherol rinse-off product also significantly inhibited photo-oxidation of squalene.⁷

A 2009 6-month study in healthy human volunteers with actinic keratoses demonstrated that while topically applied dl-alpha-tocopherol, of which cutaneous levels were significantly increased at the end of the study, did not significantly change already present lesions, alterations in polyamine metabolism revealed that squamous cell carcinogenesis potential was significantly diminished.¹⁷

Patrizi et al., in a 2015 randomized, controlled, double-blind, single center study, assessed the safety and efficacy of MD2011001 cream (a nonsteroidal topical cream including vitamin E, epigallocatechin gallate and grape seed procyanidins) versus placebo, in 44 patients with mild to moderate AD in the perioral/periocular area and/or the neck. The researchers noted a significantly more rapid reduction in affected surface area with the test formulation, compared with placebo; the product was found to be well tolerated and safe as well as effective for mild to moderate AD.¹⁸

Also that year, Ruiz-Tovar et al. performed a prospective randomized clinical trial in 60 patients, showing that topical vitamin E ointment reduced postoperative pain.¹⁹

The vitamin C, vitamin E, ferulic acid combination

Vitamin E is perceived to be more effective when used in combination with other antioxidant ingredients. Some data suggest a cumulative beneﬁt derived from using oral and topical antioxidant products in combination, including vitamins C and E in particular.^20-22 Because vitamin C can restore oxidized vitamin E, combining the antioxidants is a stabilizing factor in topical formulations.^23,24 Further, ferulic acid has been shown to stabilize both vitamins, with the topical combination yielding photoprotective effects against UVB exposure, including the significant reduction in thymine dimer formation.^9,24,25

A small study of nine patients conducted by Murray et al. in 2008 found that a stable topical preparation of 15% l-ascorbic acid, 1% alpha-tocopherol, and 0.5% ferulic acid protected human skin in vivo from UV-induced damage, specifically erythema and apoptosis. The formulation also suppressed p53 activation and limited thymine dimer mutations, which are associated with skin cancer.²⁶

Waibel et al. conducted a double-blind, prospective, single-center, randomized split-face trial in 2015 to study whether laser-assisted delivery of vitamins C and E and ferulic acid after fractional ablative laser procedures to treat photodamage could enhance wound healing. Fifteen healthy men and women (aged 30-55 years) were treated with the combination formulation on one side of the face and vehicle on the other side within 2 minutes of receiving fractional ablative CO₂ laser surgery. They also received daily treatments and evaluations during days 1 through 7 of healing. Edema was found to be diminished on the sides treated with the antioxidant combination, compared with vehicle on day 7, and erythema, on days 3 and 5.²⁷

Other vitamin E combinations

In 2014, Farris et al. found vitamin E to be a key ingredient, along with resveratrol and baicalin, in a nighttime antioxidant formulation that netted a statistically significant improvement in skin rejuvenation, specifically ameliorating fine lines and wrinkles, skin firmness, skin elasticity, skin laxity, hyperpigmentation, radiance, and skin roughness over 3 months, compared with baseline.²⁸

Pereira et al. reported in 2014 that they found that the topical application of polymeric bioadhesive films containing aloe vera and vitamin E acetate appear to be an effective approach to burn treatment.²⁹

A 2015 randomized, controlled, double-blind prospective study in 30 healthy volunteers also indicated that an SPF 30 sunscreen supplemented with an antioxidant combination containing grape seed extract, vitamin E, coenzyme Q10, and vitamin C effectively protected skin against infrared A radiation damage, unlike the use of the SPF 30 product without the antioxidant cocktail.³⁰

Conclusion

Combining vitamin E with other antioxidants appears to enhance its bioactivity and, likely, that of the other interacting antioxidants. The potential therapeutic benefits of vitamin E in preventing and treating skin cancer and photoaging remain an important focus of research. As an ingredient in topical anti-aging skin care preparations, vitamin E displays emollient properties, and is stable, easy to formulate, and relatively inexpensive, making it a popular additive. More controlled trials are necessary to fully clarify the role of vitamin E in treating various dermatoses.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever. She also developed and owns the Baumann Skin Type Solution skin typing systems and related products.

References

2. Dermatol Surg. 2005 Jul;31(7 Pt 2):805-13.

3. J Cosmet Dermatol. 2004 Jul;3(3):149-55.

4. Skin Pharmacol Appl Skin Physiol. 2001;14 Suppl 1:87-91.

5. Am J Clin Nutr. 1987 Jul;46(1 Suppl):183-6.

6. Nutr Rev. 2012 Sep;70(9):483-90.

7. Skin Pharmacol Physiol. 2005 Jan-Feb;18(1):20-6.

8. Ann Nutr Metab. 2012;61(3):207-12.

9. J Am Acad Dermatol. 2003 Jun;48(6):866-74.

10. Plast Reconstr Surg. 1997 Sep;100(4):973-80.

11. Acta Derm Venereol. 1996 Jul;76(4):264-8.

12. J Invest Dermatol. 1995 Apr;104(4):484-8.

13. Photodermatol Photoimmunol Photomed. 1990 Apr;7(2):56-62.

14. Photodermatol. 1989 Oct;6(5):228-33.

15. Drug Metab Rev. 2000 Aug-Nov;32(3-4):413-20.

16. Clin Dermatol. 2009 Sep-Oct;27(5):469-74.

17. Cancer Prev Res (Phila). 2009 Apr;2(4):394-400.

18. J Dermatolog Treat. 2015 Dec 10:1-5. [Epub ahead of print].

19. Int J Colorectal Dis. 2016 Jul;31(7):1371-2.

20. Skin Pharmacol Appl Skin Physiol. 15:307;2002.

21. Biofactors. 2003;18(1-4):289-97.

22. J Drugs Dermatol. 2008 Jul;7(7 Suppl):s2-6.

23. Can J Physiol Pharmacol. 1993 Sep;71(9):725-31.

24. PLoS One. 2013 May 14;8(5):e63809.

25. J Invest Dermatol. 2005 Oct;125(4):826-32.

26. J Am Acad Dermatol. 2008 Sep;59(3):418-25.

27. Lasers Surg Med. 2016 Mar;48(3):238-44.

28. J Drugs Dermatol. 2014 Dec;13(12):1467-72.

29. Biomed Res Int. 2014;2014:641590.

30. Photochem Photobiol. 2015 Jan-Feb;91(1):248-50.

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1. J Mol Med (Berl). 1995 Jan;73(1):7-17.

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Topical uses and findings

Also that year, Ruiz-Tovar et al. performed a prospective randomized clinical trial in 60 patients, showing that topical vitamin E ointment reduced postoperative pain.¹⁹

The vitamin C, vitamin E, ferulic acid combination

Other vitamin E combinations

Conclusion

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever. She also developed and owns the Baumann Skin Type Solution skin typing systems and related products.

References

2. Dermatol Surg. 2005 Jul;31(7 Pt 2):805-13.

3. J Cosmet Dermatol. 2004 Jul;3(3):149-55.

4. Skin Pharmacol Appl Skin Physiol. 2001;14 Suppl 1:87-91.

5. Am J Clin Nutr. 1987 Jul;46(1 Suppl):183-6.

6. Nutr Rev. 2012 Sep;70(9):483-90.

7. Skin Pharmacol Physiol. 2005 Jan-Feb;18(1):20-6.

8. Ann Nutr Metab. 2012;61(3):207-12.

9. J Am Acad Dermatol. 2003 Jun;48(6):866-74.

10. Plast Reconstr Surg. 1997 Sep;100(4):973-80.

11. Acta Derm Venereol. 1996 Jul;76(4):264-8.

12. J Invest Dermatol. 1995 Apr;104(4):484-8.

13. Photodermatol Photoimmunol Photomed. 1990 Apr;7(2):56-62.

14. Photodermatol. 1989 Oct;6(5):228-33.

15. Drug Metab Rev. 2000 Aug-Nov;32(3-4):413-20.

16. Clin Dermatol. 2009 Sep-Oct;27(5):469-74.

17. Cancer Prev Res (Phila). 2009 Apr;2(4):394-400.

18. J Dermatolog Treat. 2015 Dec 10:1-5. [Epub ahead of print].

19. Int J Colorectal Dis. 2016 Jul;31(7):1371-2.

20. Skin Pharmacol Appl Skin Physiol. 15:307;2002.

21. Biofactors. 2003;18(1-4):289-97.

22. J Drugs Dermatol. 2008 Jul;7(7 Suppl):s2-6.

23. Can J Physiol Pharmacol. 1993 Sep;71(9):725-31.

24. PLoS One. 2013 May 14;8(5):e63809.

25. J Invest Dermatol. 2005 Oct;125(4):826-32.

26. J Am Acad Dermatol. 2008 Sep;59(3):418-25.

27. Lasers Surg Med. 2016 Mar;48(3):238-44.

28. J Drugs Dermatol. 2014 Dec;13(12):1467-72.

29. Biomed Res Int. 2014;2014:641590.

30. Photochem Photobiol. 2015 Jan-Feb;91(1):248-50.

Topical uses and findings

Also that year, Ruiz-Tovar et al. performed a prospective randomized clinical trial in 60 patients, showing that topical vitamin E ointment reduced postoperative pain.¹⁹

The vitamin C, vitamin E, ferulic acid combination

Other vitamin E combinations

Conclusion

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever. She also developed and owns the Baumann Skin Type Solution skin typing systems and related products.

References

1. J Mol Med (Berl). 1995 Jan;73(1):7-17.

2. Dermatol Surg. 2005 Jul;31(7 Pt 2):805-13.

3. J Cosmet Dermatol. 2004 Jul;3(3):149-55.

4. Skin Pharmacol Appl Skin Physiol. 2001;14 Suppl 1:87-91.

5. Am J Clin Nutr. 1987 Jul;46(1 Suppl):183-6.

6. Nutr Rev. 2012 Sep;70(9):483-90.

7. Skin Pharmacol Physiol. 2005 Jan-Feb;18(1):20-6.

8. Ann Nutr Metab. 2012;61(3):207-12.

9. J Am Acad Dermatol. 2003 Jun;48(6):866-74.

10. Plast Reconstr Surg. 1997 Sep;100(4):973-80.

11. Acta Derm Venereol. 1996 Jul;76(4):264-8.

12. J Invest Dermatol. 1995 Apr;104(4):484-8.

13. Photodermatol Photoimmunol Photomed. 1990 Apr;7(2):56-62.

14. Photodermatol. 1989 Oct;6(5):228-33.

15. Drug Metab Rev. 2000 Aug-Nov;32(3-4):413-20.

16. Clin Dermatol. 2009 Sep-Oct;27(5):469-74.

17. Cancer Prev Res (Phila). 2009 Apr;2(4):394-400.

18. J Dermatolog Treat. 2015 Dec 10:1-5. [Epub ahead of print].

19. Int J Colorectal Dis. 2016 Jul;31(7):1371-2.

20. Skin Pharmacol Appl Skin Physiol. 15:307;2002.

21. Biofactors. 2003;18(1-4):289-97.

22. J Drugs Dermatol. 2008 Jul;7(7 Suppl):s2-6.

23. Can J Physiol Pharmacol. 1993 Sep;71(9):725-31.

24. PLoS One. 2013 May 14;8(5):e63809.

25. J Invest Dermatol. 2005 Oct;125(4):826-32.

26. J Am Acad Dermatol. 2008 Sep;59(3):418-25.

27. Lasers Surg Med. 2016 Mar;48(3):238-44.

28. J Drugs Dermatol. 2014 Dec;13(12):1467-72.

29. Biomed Res Int. 2014;2014:641590.

30. Photochem Photobiol. 2015 Jan-Feb;91(1):248-50.

References

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Update on vitamin E

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• Copiously available through the diet, this main lipid-soluble antioxidant in human skin is used to treat some dermatoses but is not approved by the Food and Drug Administration for skin conditions.

• Its lipophilic nature renders it suitable for topical application and percutaneous absorption.

• Topical uses include skin hydration and treatment of atopic dermatitis.

• It is thought to be most effective when used with other antioxidant ingredients, particularly vitamin C and ferulic acid, with the combination yielding photoprotective activity.

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Update on green tea

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Update on green tea

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1. Cancer Lett. 1997 Mar 19;114(1-2):315-7.

During the last 25 years, green tea, which is derived from Camellia sinensis (an evergreen member of the Theaceae family), has gained considerable attention because of its purported antioxidant and anticarcinogenic properties. Believed to have been used by human beings for 4,000 years,¹ green tea is now one of the most heavily researched of the antioxidants, with numerous studies of its cutaneous effects appearing in the literature.² Laden with plant polyphenols, orally administered or topically applied green tea has been shown to display significant antioxidant, chemopreventive, immunomodulatory, and anti-inflammatory activity, affecting the biochemical pathways important in cell proliferation.^3-6 For this reason, and due to its global popularity as a beverage, green tea polyphenols are among the most frequently studied herbal agents used in medicine.

Polyphenols, many of which are potent antioxidants, are a large diverse family of thousands of chemical compounds present in plants. The four major polyphenolic catechins present in green tea include: ECG [(-)EpiCatechin-3-O-Gallate], GCG [(-)GalloCatechin-3-O-Gallate], EGC [(-)EpiGalloCatechin], and EGCG [(-)EpiGalloCatechin-3-O-Gallate], the most abundant and biologically active green tea constituent. In fact, EGCG is the component associated with the greatest anticarcinogenic and chemopreventive properties.⁶

A wide-ranging evidence-based review of the use of botanicals in dermatology, published in 2010, showed that the oral administration, in particular, as well as topical application of antioxidant plant extracts of green tea, among other botanicals, can protect skin against the harmful effects of UV exposure, including erythema, premature aging, and cancer.⁷

Green tea is thought to be challenging to formulate because of the inherent hydrophilicity of EGCG, which limits penetration into human skin.^8,9 Nevertheless, green tea is thought to have great potential in traditional sunscreens to enhance photoprotection.^10,11 The photoprotective activity of orally administered or topically applied green tea has been supported in various studies.^12-15

The remainder of this column will focus on recent studies of topically applied green tea polyphenols in human beings as well as clinical uses of this agent.

Topical uses

Topical green tea appears to reduce skin inflammation and neutralize free radicals, which explains its popularity as an additive in rosacea and antiaging skin care products. The antiaging effects of green tea are difficult to measure because it functions as an antioxidant that prevents aging and does not have the capacity to increase collagen synthesis or ameliorate already existing wrinkles. However, there is relatively good evidence, in comparison to other antioxidants, suggesting that topically applied green tea can help protect skin from UV radiation.¹⁶

Investigators performed a thorough literature search of all in vitro, in vivo, and controlled clinical trials involving green tea formulations and their dermatologic applications, which was published in 2012. They evaluated 20 studies, with evidence suggesting that orally administered green tea displays a broad range of healthy activity, and supportive data for the use of topically applied green tea extract for treatment of various cutaneous conditions, including acne, rosacea, atopic dermatitis, androgenetic alopecia, hirsutism, candidiasis, keloids, leishmaniasis, and genital warts.¹⁷

Also, a green tea topical formulation, green tea sinecatechin Polyphenon E (Veregen) ointment, has recently been shown to exert antioxidant, antiviral, and antitumor activity, and has demonstrated efficacy in treating Condylomata acuminata (external anogenital warts).¹⁸ In addition, topically applying green tea catechins in the morning in combination with traditional sunscreens is believed to have the potential to protect the skin from UV-induced damage. Topical green tea may improve rosacea, prevent retinoid dermatitis, and play a role in managing pigmentation disorders. Few of the many over-the-counter products that contain green tea catechins have been tested in controlled clinical trials and the concentration of polyphenols in these products is too low to demonstrate efficacy. It is necessary to know the amount of green tea catechins in a formulation to judge its efficacy.

Acne

In 2009, in a 6-week study investigating the efficacy of 2% green tea lotion for the treatment of mild-to-moderate acne vulgaris in 20 patients, researchers reported statistically significant reductions in mean total lesion count and mean severity index (devised by the authors to correlate with total lesion count in increasing intensity, scaled from 1 to 3). They concluded that 2% green tea lotion is both an effective and cost effective approach for treating mild-to-moderate acne lesions.¹⁹

A 2012 study revealed that ethanol extracts of several herbs, including green tea, exhibited the potential for inhibiting acne when incorporated into a topical moisturizer, specifically acting against acne-causing bacteria without provoking irritation.²⁰ Earlier that year, other investigators conducted in vitro and in vivo experiments to evaluate the effects against acne of polyphenon-60, which contains various green tea catechins (now referred to as sinecatechins in the United States.).²¹ In this clinical study, patients exhibited improvement in acne symptoms, including a reduction in the number of pustules and comedones.²²

A study published in 2013, a single-blind, placebo-controlled, split-face comparative study in 22 individuals over 60 days, evaluated the efficacy of green tea, as well as green tea plus lotus, compared with placebo for controlling casual sebum secretions in healthy adults. Compared with placebo, consistent and statistically significant decreases in sebum secretions were observed in both treatment groups. The combination of green tea and lotus extracts also achieved statistically sounder results than green tea alone. The investigators concluded that a synergistic interaction between green tea and lotus extract constituents appears to hold promise for the treatment of skin conditions in which elevated sebum levels are involved.²³

Anogenital warts

In 2006, the Food and Drug Administration approved for the first time a botanical drug formulation for the topical treatment of genital and perianal warts: sinecatechins, derived from green tea catechins and other C. sinensis constituents in a topical 15% ointment (Veregen).^{21, 24-28}

Two years later, Tatti et al. conducted a randomized, double-blind, vehicle-controlled trial to evaluate the efficacy of topical sinecatechins in 502 male and female patients (aged 18 years and older) for the treatment of anogenital warts. For 16 weeks or until complete clearance, subjects applied sinecatechins ointment 15% or 10% or vehicle (placebo) three times daily. Complete clearance was achieved in 57.2% of patients treated with 15% ointment, 56.3% using 10% ointment, and 33.7% who used only the vehicle. Respective recurrence rates, after 12 weeks, were 6.5%, 8.3%, and 8.8%. The investigators concluded that topical sinecatechins in 15% and 10% concentrations represent effective and well-tolerated options for anogenital wart treatment.²⁹

Similarly favorable results regarding polyphenon E 15% were reported in reference to three placebo-controlled clinical studies in 1,400 patients with genital warts from Europe, North and South America, and South Africa,^30,31 and by Tatti et al. again in 2010 after randomized, double-blind, vehicle-controlled safety and efficacy trials in nearly 1,000 patients treated with polyphenon E 15% and 10% formulations.²¹

Two years later, investigators evaluated sinecatechins (Polyphenon E) 10% ointment in two double-blind, multinational studies in adults with external genital and perianal warts. Polyphenon E 10% was found to be significantly more effective than vehicle in completely or partially clearing all warts.³²

Earlier that year, a review of the use of sinecatechins ointment for the treatment of external anogenital warts noted that while clearance rates are similar among sinecatechins and other indicated topical medications such as imiquimod and podophyllotoxin, recurrence rates are lower for patients treated with sinecatechins. The authors concluded that the use of sinecatechins for condylomata acuminata was safe and effective and its various molecular activities suggest broader applications to other viral and tumor lesions.³³

In 2015, Gupta and Daigle reported that sinecatechins 10% ointment for the treatment of external genital warts was found in phase III trials to display greater efficacy and lower rates of recurrence in comparison to patient-applied treatments now available.²⁸ Later that year, in a systematic PubMed and Embase review of clinical trials involving the use of polyphenol-based therapies, Tuong et al. identified cogent evidence suggesting the effectiveness of green tea polyphenols for the treatment of anogenital warts.³⁴

Antiaging activity

Green tea has been shown to work in combination with red light to exert a rejuvenating effect on the skin, as Sommer and Zhu reported in 2009 that green tea filled cotton pads applied once daily for 20 minutes prior to treatment with light-emitting diodes (central wavelength 670 nm, dermal dose 4 J/cm²) reduced wrinkles in 1 month comparably to 10 months of light treatment alone.³⁵

In 2013, Hong et al. studied the antiwrinkle effects of topically applied green tea extract with high antioxidant activity after tannase treatment. Study participants were randomly divided to receive either green tea extract or tannase-converted green tea extract on their crow’s feet for an 8-week period. The investigators found that tannase treatment elevated the antioxidant activity of green tea and imparted antiwrinkle effects.³⁶

At around the same time, Gianeti conducted clinical studies in 24 volunteers to assess the effects of a cosmetic formulation containing 6% C. sinensis glycolic leaf extracts. Skin moisture was enhanced after 30 days of topical application as was the viscoelastic-to-elastic ratio compared with vehicle and control (a forearm area left untreated). Skin roughness was significantly diminished after 30 days. The investigators concluded that the topical cosmetic formulation with green tea yielded salient moisturizing and cutaneous microrelief benefits.³⁷

Also in 2013, oral intake of green tea catechins in 16 healthy human subjects (with 14 completing the study) appeared to result in the integration of catechin metabolites into human skin linked to the negation of UV-induced 12-hydroxyeicosatetraenoic acid (12-HETE). The investigators speculated that this incorporation of catechins may render protection against sunburn inflammation and even cumulative UV-induced harm.³⁸

After earlier showing the efficacy of green tea and lotus extracts in skin disorders involving excess sebum in a single-blinded, placebo-controlled, split-face comparative study,²³ Mahmood and Akhtar conducted a 60-day placebo-controlled comparative split-face study in 33 healthy Asian men to evaluate the efficacy of two cosmetic formulations (green tea and lotus extract) for facial wrinkles. All of the formulations yielded improvements in skin roughness, scaliness, smoothness, and wrinkling, with the greatest reduction in wrinkling conferred by the combination formulation. The investigators concluded that the synergistic activity of green tea and lotus extracts exerted significant improvement along several skin parameters, suggesting the potential for these ingredients in antiaging products.³⁸

In 2014, the synergistic effects of green tea and ginkgo biloba were explored in preclinical and clinical studies. In the clinical study, 48 participants applied the formulations on forearm skin and were evaluated before and after 3 hours and following 15- and 30-day use periods. Results showed a moisturizing effect and enhancement in skin microrelief, as well as improvements in skin elasticity and barrier function.³

Conclusion

Green tea remains one of the most researched antioxidants as benefits from its use continue to emerge. Indeed, green tea polyphenols are in use for a growing number of indications, especially acne and anogenital warts, and there is reason for optimism that topically applied green tea will gain momentum as an increasingly selected therapeutic option. More clinical studies are necessary to further establish the potential role of green tea for a wider range of cutaneous indications. Green tea holds particular promise in relation to photoprotection against UV-induced skin cancer and skin aging.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever. She also developed and owns the Baumann Skin Type Solution skin typing systems and related products

References:

2. J Am Acad Dermatol. 2005 Jun;52(6):1049-59.

3. Arch Dermatol. 2000 Aug;136(8):989-94.

4. Photochem Photobiol. 1995 Nov;62(5):855-61.

5. Oxid Med Cell Longev. 2012:2012:560682.

6. J Dtsch Dermatol Ges. 2015 Aug;13(8):768-75.

7. Am J Clin Dermatol. 2010;11(4):247-67.

8. Dermatol Ther. 2007 Sep-Oct;20(5):322-9.

9. J Clin Aesthet Dermatol. 2010 Feb;3(2):22-41.

10. Photodermatol Photoimmunol Photomed. 2007 Feb;23(1):48-56.

11. Skin Res Technol. 2009 Aug;15(3):338-45.

12. Exp Dermatol. 2009 Jan;18(1):69-77.

13. Exp Dermatol. 2009 Jun;18(6):522-6.

14. Arch Biochem Biophys. 2011 Apr 15;508(2):152-8.

15. Cancer Prev Res (Phila). 2010 Feb;3(2):179-89.

16. Complement Ther Clin Pract. 2014 Feb;20(1):11-5.

17. Skinmed. 2012 Nov-Dec;10(6):352-5.

18. J Eur Acad Dermatol Venereol. 2011 Mar;25(3):345-53.

19. J Drugs Dermatol. 2009 Apr;8(4):358-64.

20. Pak J Pharm Sci. 2012 Oct;25(4):867-70.

21. Br J Dermatol. 2010 Jan;162(1):176-84.

22. Arch Dermatol Res. 2012 Oct;304(8):655-63.

23. Hippokratia. 2013 Jan;17(1):64-7.

24. Food Chem Toxicol. 2008 Aug;46(8):2606-10.

25. Nat Biotechnol. 2008 Oct;26(10):1077-83.

26. Skin Therapy Lett. 2012 Apr;17(4):5-7.

27. J Clin Aesthet Dermatol. 2012 Jan;5(1):19-26.

28. Skin Therapy Lett. 2015 Jan-Feb;20(1):6-8.

29. Obstet Gynecol. 2008 Jun;111(6):1371-9.

30. Hautarzt. 2008 Jan;59(1):31-5.

31. J Eur Acad Dermatol Venereol. 2007 Nov;21(10):1404-12.

32. Am J Clin Dermatol. 2012 Aug 1:13(4):275-81.

33. Expert Opin Biol Ther. 2012 Jun;12(6):783-93.

34. J Dermatolog Treat. 2015;26(4):381-8.

35. Photomed Laser Surg. 2009 Dec;27(6):969-71.

36. J Cosmet Dermatol. 2013 Jun;12(2):137-43.

37. Dermatol Ther. 2013 May-Jun;26(3):267-71.

38. Rejuvenation Res. 2013 Apr;16(2):91-7.

39. J Drugs Dermatol. 2014 Sep;13(9):1092-7.

References

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Read more about Update on green tea

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1. Cancer Lett. 1997 Mar 19;114(1-2):315-7.

Author and Disclosure Information

The remainder of this column will focus on recent studies of topically applied green tea polyphenols in human beings as well as clinical uses of this agent.

Topical uses

Acne

Anogenital warts

Antiaging activity

Conclusion

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever. She also developed and owns the Baumann Skin Type Solution skin typing systems and related products

References:

2. J Am Acad Dermatol. 2005 Jun;52(6):1049-59.

3. Arch Dermatol. 2000 Aug;136(8):989-94.

4. Photochem Photobiol. 1995 Nov;62(5):855-61.

5. Oxid Med Cell Longev. 2012:2012:560682.

6. J Dtsch Dermatol Ges. 2015 Aug;13(8):768-75.

7. Am J Clin Dermatol. 2010;11(4):247-67.

8. Dermatol Ther. 2007 Sep-Oct;20(5):322-9.

9. J Clin Aesthet Dermatol. 2010 Feb;3(2):22-41.

10. Photodermatol Photoimmunol Photomed. 2007 Feb;23(1):48-56.

11. Skin Res Technol. 2009 Aug;15(3):338-45.

12. Exp Dermatol. 2009 Jan;18(1):69-77.

13. Exp Dermatol. 2009 Jun;18(6):522-6.

14. Arch Biochem Biophys. 2011 Apr 15;508(2):152-8.

15. Cancer Prev Res (Phila). 2010 Feb;3(2):179-89.

16. Complement Ther Clin Pract. 2014 Feb;20(1):11-5.

17. Skinmed. 2012 Nov-Dec;10(6):352-5.

18. J Eur Acad Dermatol Venereol. 2011 Mar;25(3):345-53.

19. J Drugs Dermatol. 2009 Apr;8(4):358-64.

20. Pak J Pharm Sci. 2012 Oct;25(4):867-70.

21. Br J Dermatol. 2010 Jan;162(1):176-84.

22. Arch Dermatol Res. 2012 Oct;304(8):655-63.

23. Hippokratia. 2013 Jan;17(1):64-7.

24. Food Chem Toxicol. 2008 Aug;46(8):2606-10.

25. Nat Biotechnol. 2008 Oct;26(10):1077-83.

26. Skin Therapy Lett. 2012 Apr;17(4):5-7.

27. J Clin Aesthet Dermatol. 2012 Jan;5(1):19-26.

28. Skin Therapy Lett. 2015 Jan-Feb;20(1):6-8.

29. Obstet Gynecol. 2008 Jun;111(6):1371-9.

30. Hautarzt. 2008 Jan;59(1):31-5.

31. J Eur Acad Dermatol Venereol. 2007 Nov;21(10):1404-12.

32. Am J Clin Dermatol. 2012 Aug 1:13(4):275-81.

33. Expert Opin Biol Ther. 2012 Jun;12(6):783-93.

34. J Dermatolog Treat. 2015;26(4):381-8.

35. Photomed Laser Surg. 2009 Dec;27(6):969-71.

36. J Cosmet Dermatol. 2013 Jun;12(2):137-43.

37. Dermatol Ther. 2013 May-Jun;26(3):267-71.

38. Rejuvenation Res. 2013 Apr;16(2):91-7.

39. J Drugs Dermatol. 2014 Sep;13(9):1092-7.

The remainder of this column will focus on recent studies of topically applied green tea polyphenols in human beings as well as clinical uses of this agent.

Topical uses

Acne

Anogenital warts

Antiaging activity

Conclusion

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever. She also developed and owns the Baumann Skin Type Solution skin typing systems and related products

References:

1. Cancer Lett. 1997 Mar 19;114(1-2):315-7.

2. J Am Acad Dermatol. 2005 Jun;52(6):1049-59.

3. Arch Dermatol. 2000 Aug;136(8):989-94.

4. Photochem Photobiol. 1995 Nov;62(5):855-61.

5. Oxid Med Cell Longev. 2012:2012:560682.

6. J Dtsch Dermatol Ges. 2015 Aug;13(8):768-75.

7. Am J Clin Dermatol. 2010;11(4):247-67.

8. Dermatol Ther. 2007 Sep-Oct;20(5):322-9.

9. J Clin Aesthet Dermatol. 2010 Feb;3(2):22-41.

10. Photodermatol Photoimmunol Photomed. 2007 Feb;23(1):48-56.

11. Skin Res Technol. 2009 Aug;15(3):338-45.

12. Exp Dermatol. 2009 Jan;18(1):69-77.

13. Exp Dermatol. 2009 Jun;18(6):522-6.

14. Arch Biochem Biophys. 2011 Apr 15;508(2):152-8.

15. Cancer Prev Res (Phila). 2010 Feb;3(2):179-89.

16. Complement Ther Clin Pract. 2014 Feb;20(1):11-5.

17. Skinmed. 2012 Nov-Dec;10(6):352-5.

18. J Eur Acad Dermatol Venereol. 2011 Mar;25(3):345-53.

19. J Drugs Dermatol. 2009 Apr;8(4):358-64.

20. Pak J Pharm Sci. 2012 Oct;25(4):867-70.

21. Br J Dermatol. 2010 Jan;162(1):176-84.

22. Arch Dermatol Res. 2012 Oct;304(8):655-63.

23. Hippokratia. 2013 Jan;17(1):64-7.

24. Food Chem Toxicol. 2008 Aug;46(8):2606-10.

25. Nat Biotechnol. 2008 Oct;26(10):1077-83.

26. Skin Therapy Lett. 2012 Apr;17(4):5-7.

27. J Clin Aesthet Dermatol. 2012 Jan;5(1):19-26.

28. Skin Therapy Lett. 2015 Jan-Feb;20(1):6-8.

29. Obstet Gynecol. 2008 Jun;111(6):1371-9.

30. Hautarzt. 2008 Jan;59(1):31-5.

31. J Eur Acad Dermatol Venereol. 2007 Nov;21(10):1404-12.

32. Am J Clin Dermatol. 2012 Aug 1:13(4):275-81.

33. Expert Opin Biol Ther. 2012 Jun;12(6):783-93.

34. J Dermatolog Treat. 2015;26(4):381-8.

35. Photomed Laser Surg. 2009 Dec;27(6):969-71.

36. J Cosmet Dermatol. 2013 Jun;12(2):137-43.

37. Dermatol Ther. 2013 May-Jun;26(3):267-71.

38. Rejuvenation Res. 2013 Apr;16(2):91-7.

39. J Drugs Dermatol. 2014 Sep;13(9):1092-7.

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• Green tea is one of the most researched antioxidants, particularly its constituent polyphenolic catechins (notably epigallocatechin gallate, or EGCG).

• It is thought to be difficult to formulate in topical products because of the intrinsic hydrophilicity of EGCG.

• Topical application is thought to reduce inflammation and neutralize free radicals, but does not increase collagen production or reduce already existing wrinkles.

• It has been shown to be effective topically for treating acne, anogenital warts, and aging skin.

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Sell skin care products to protect your patients

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The ethics behind selling skin care products to patients has been hotly debated within the field of cosmetic dermatology for several decades. In 15 years of practice, I have come to the conclusion that patients want you to and need you to because otherwise they are easily taken advantage of. Other physicians are doing it but we – the dermatologists – are the most qualified to offer skin care advice. This article will discuss the reasons that you need to get over the ethical dilemma and offer skin care to your patients.

Using the correct skin care regimen for the face and body will improve outcomes

Whether a patient suffers from acne, rosacea, melasma, psoriasis, eczema, contact dermatitis, or even tinea versicolor, using the proper skin care regimen will improve outcomes by affecting the skin barrier, pH, hydration level, and function of the keratinocytes and fibroblasts. In fact, every personal care product that touches the skin has an impact on skin health. For example, if a patient uses a detergent-laden bar soap, the skin barrier will be impaired, which can cause them to react to allergens and irritants. Personal care products can affect the skin pH; this is shown to play a role in Malassezia colonization in atopic dermatitis patients (J Clin Med. 2015;4[6]:1217-28). As dermatologists, we know better than anyone that daily use of SPF improves skin health and lowers the risk of postinflammatory pigmentation. We all agree that patients should cleanse the skin and apply a SPF every day. Giving them guidance about which to choose is very important.

Giving the patient exact instructions will lead to improved compliance

Why should recommending skin care products be perceived differently than prescribing a prescription medication? We should prescribe to our patients in writing the exact skin care regimen they should use for their face or body to ensure that they understand the directions. I have been surprised by patients who have said, “I did not know I was supposed to wash my cleanser off,” or “I wash my face with hand soap.” We can help them by educating them and giving them specific instructions. Improved education and communication results in increased compliance. When you do surgery on a wound, you probably tell them to apply a topical antibiotic ointment, but do you direct them to what cleanser to use or tell them which SPF to use on the stitched wound? Providing written instructions for all dermatologic disorders and postprocedure care is necessary to improve compliance and outcomes.

Combine cosmeceuticals, prescription medications, and medical procedures

You (unlike the cosmetic counter salesperson) have the ability to combine cosmeceuticals with prescription medications and medical procedures. In fact, selling your patients the right skin care products to use after a procedure saves them a trip to the store and ensures that they use the correct products. Of course it makes sense that patients getting toxins and fillers should use a retinoid to improve skin aging; however, many general dermatologic diseases would improve with the proper skin care. For example, do you use biologics for psoriasis? Using the proper skin care to regulate skin pH and improve the skin barrier may help prevent colonization of yeast, fungus, and bacteria. The same is true for atopic patients. Do you use liquid nitrogen? Studies show that using a retinoid before a procedure speeds healing. Skin care goes way beyond wrinkles and dark circles under the eyes, so if you are not prescribing the patient an exact regimen, you are not maximizing outcomes.

I don’t have time to talk to my patients about skin care

The missing piece is that most of us don’t have the time to spend discussing skin care. This is where using a standardized scientific methodology is crucial. I developed and use a skin typing methodology in my office and have seen improved physician/patient relationships and increased patient satisfaction resulting in a significant amount of referrals. We also have noted decreased call backs and fewer adverse events from products because the patients have a better understanding of how to properly apply the cosmeceuticals and prescription products. The best part is, it does not add any time onto the patient visit when standardized methodologies are properly adopted.

What if I still do not feel comfortable profiting from the sale of skin care products?

First you need to realize that time is money and you are saving the patient the cost in time it would have taken them to go to a store, park, and shop for the correct product. I have seen data presented from several companies that show that patients usually spend a large amount of money on skin care products after they see their dermatologist. Without guidance, they will likely buy the incorrect products. If they buy the wrong product, you save them the hassle of having to make another office visit and the aggravation of the side effects from the incorrect product. These are often of poor quality or not appropriate for their skin issues. Counterfeit products are rampant on the Internet and many new companies tout worthless products with stem cells and other nonsense. Only you can help your patients make sure that money is spent on the proper products.

Conclusion

Do you really want someone else giving your patients skin care advice? Your patients deserve to have someone with your insights, knowledge, compassion, and honesty help them achieve optimal skin health through use of the proper cosmeceuticals and prescription medications. It is up to you and your staff to save your patients from falling prey to persuasive salespeople with no scientific knowledge or concern for long-term skin health.

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Using the correct skin care regimen for the face and body will improve outcomes

Giving the patient exact instructions will lead to improved compliance

Combine cosmeceuticals, prescription medications, and medical procedures

I don’t have time to talk to my patients about skin care

What if I still do not feel comfortable profiting from the sale of skin care products?

Conclusion

Using the correct skin care regimen for the face and body will improve outcomes

Giving the patient exact instructions will lead to improved compliance

Combine cosmeceuticals, prescription medications, and medical procedures

I don’t have time to talk to my patients about skin care

What if I still do not feel comfortable profiting from the sale of skin care products?

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• Most skin care products that patients buy are not appropriate for their skin issues.

• Dermatologists have the most knowledge and insights to prescribe skin care.

• Giving specific skin care instructions helps improve communication.

• Increased communication improves outcomes.

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Vitamin C

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1. J Biol Chem. 1994 May 6;269(18):13685-8.

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Vitamin C

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Leslie Baumann, MD

Vitamin C (ascorbic acid) is one of the four most important ingredients in skin care products.

• It is proven to increase collagen production when applied topically to skin.

• It inhibits tyrosinase to even skin tone and has a strong antioxidant activity.

• It is absorbed well orally, but not enough gets to the skin.

• It is best absorbed at a pH of 2.0.

• It is unstable when exposed to light and air. Instruct patients to discard 6 months after opening.

In addition, the proper formulation is patented and expensive. Stick with brands you trust. Use vitamin C on skin prior to procedures to speed healing. It will sting when used on inflamed skin because of the low pH.

In my opinion, all patients need to be on the proper skin care regimen for their skin type. This includes a daily sun protection factor (SPF), a cleanser, a retinoid, and an antioxidant. Ascorbic acid is one of my favorite antioxidants because it is the only one shown to increase the production of collagen by fibroblasts and inhibit tyrosinase while scavenging free radicals. Sure it is expensive – but that is because formulating and packaging it properly is expensive. Unfortunately, many subpar brands have entered the market. Ask to see the company’s research data on its formulation before choosing to recommend or sell ascorbic acid/vitamin C in your practice.

An essential water-soluble nutrient for the development of bone and connective tissue, vitamin C is found in citrus fruits and green leafy vegetables. It is produced in most plants and animals, but a mutated gene in humans has resulted in a deficiency of L-gulono-gamma-lactone oxidase, the enzyme required for its production.^1,2 Although ascorbic acid cannot be synthesized by the human body, dietary consumption renders it the most abundant antioxidant in human skin and blood, and vitamin C plays an important role in endogenous collagen production and the inhibition of collagen degradation.^3-6 Ascorbic acid also is known to regenerate alpha-tocopherol (vitamin E) levels and, therefore, is thought to protect against diseases related to oxidative stress.⁷

Epidermal vitamin C can be depleted by sunlight and environmental pollution, such as ozone in urban pollution.^8,9 Known to exhibit a wide range of biologic activities, ascorbic acid has been shown to deliver rejuvenating effects on skin wrinkles, texture, strength, and evenness of tone through its antioxidant, tyrosinase-inhibiting, and collagen production-promoting activities.¹⁰ Indeed, as a topical agent, vitamin C has been used to prevent photodamage, and to treat melasma, striae alba, and postoperative erythema in laser patients.^11,12 It is regularly used to treat aging skin, and as a depigmenting agent.^2,10,13 This column will discuss the antioxidant, antiaging, and depigmenting activity of vitamin C in the context of recent human studies.

Antioxidant and anti-aging activity

Vitamin C is unique among antioxidants because of its ability to increase collagen production in addition to its free radical scavenging antioxidant activity. Due to its capacity to interfere with the UV-induced generation of reactive oxygen species by reacting with the superoxide anion or the hydroxyl radical, vitamin C has become a popular addition to “after-sun” products,^14,15 and been shown to be effective in mitigating the effects of UVB, such as erythema and signs of photoaging, on porcine and human skin.^2,16-17

A 2001 study in 10 postmenopausal women by Nusgens et al. found that daily topical application of 5% L-ascorbic acid enhanced the levels of procollagen types I and III, their posttranslational maturation enzymes, and tissue inhibitor of matrix metalloproteinase.¹⁸ This led to increased levels of collagen in the skin.

In 2003, Humbert et al. conducted a 6-month, double-blind, vehicle-controlled trial with 20 healthy female volunteers showing that patients treated with 5% vitamin C cream experienced significant improvements in deep furrows on the neck and forearms.¹⁹

In a small study of nine adults with Fitzpatrick skin types II or III in 2008, Murray et al. studied whether a stable topical preparation of 15% L-ascorbic acid, 1% alpha-tocopherol, and 0.5% ferulic acid could protect human skin in vivo from UV-induced damage. They found that the antioxidant formulation supplemented the antioxidant pool of the skin and conferred significant photoprotection, guarding the skin against erythema and apoptosis as well as effectively suppressing p53 activation and reducing thymine dimer mutations known to be associated with skin cancer.¹³

In 2012, Xu et al. evaluated the efficacy and safety of topical 23.8% L-ascorbic acid on photoaged skin in a split-face study of 20 Chinese women. Significant improvements in fine lines, dyspigmentation, and surface roughness were observed, without adverse side effects.²⁰

In a 2015 study of 60 healthy female subjects, Crisan et al. used high-frequency ultrasound to determine that the use of a topical vitamin C formulation yielded significant increases in collagen synthesis, revealing the solution to be an effective rejuvenation therapy.²¹

Skin lightening activity

Melasma

In 2004, Espinal-Perez et al. conducted a double-blind randomized trial of 5% ascorbic acid, compared with 4% hydroquinone (HQ) water–oil emulsion in 16 female patients with melasma, aged 23-43 years (mean 36 years). Of those treated with vitamin C, 62.5% exhibited good or excellent subjectively assessed skin lightening. There was no statistically significant difference in depigmenting activity in the HQ group, of which 68.7% experienced irritation whereas vitamin C was well tolerated.²²

In a randomized, double-blind, placebo-controlled study, researchers used iontophoresis to enhance the penetration of vitamin C into the skin and significantly reduce pigmentation, compared with placebo.²³

Although ascorbic acid is viewed by many as ineffective as a depigmenting agent alone, particularly in 5%-10% concentrations, when used in combination with other ingredients such as HQ, it is considered effective.²⁴ In the magnesium-L-ascorbyl-2-phosphate esterified form, however, vitamin C is among the most popular prescribed depigmenting agents around the world, especially in countries where HQ and its derivatives are prohibited.²⁵ In a 2009 16-week open-label study by Hwang et al. of 25% L-ascorbic acid and a chemical penetration enhancer for treating melasma in 40 patients, researchers observed significant reductions in pigmentation.²⁶

In a small split-face study early in 2015, Lee et al. showed that the combination of 1,064-nm Q-switched neodymium-doped yttrium aluminum garnet (QS-Nd:YAG) laser and ultrasonic application of vitamin C was more effective than was the laser treatment alone in achieving a cosmetically acceptable treatment for melasma.²⁷

PIPA

Vitamin C can be used to diminish or prevent post-inflammatory pigment alteration (PIPA) after procedures because it inhibits tyrosinase, lowers inflammation, and quenches free radicals. In a study of 10 patients, the application of topical vitamin C 2 or more weeks after surgery reduced the duration and degree of erythema after skin resurfacing with a carbon dioxide laser.²⁸

Stretch marks

The depigmenting effects of vitamin C can lighten the pigmentation associated with stretch marks and its anti-inflammatory activity can contribute to blunting related redness.¹²

Conclusion

Although orally administered ascorbic acid is readily bioavailable, ascorbic acid in the skin is quickly depleted and oral supplementation alone does not yield optimal skin levels. Therefore, topical use of vitamin C is desirable. In fact, I tell my patients to use it topically in the morning and add a vitamin C supplement to their diet. Numerous formulation considerations (e.g., packaging, exposure to air or light during use, skin sensitivity, and user preference) are involved in the stabilization and effective penetration of ascorbic acid into the skin, and the process of developing, manufacturing, and packaging of effective, stable vitamin C products is expensive.

Vitamin C, particularly when combined with other ingredients, has been shown to be an integral constituent in topical antioxidant, antiaging, and depigmenting formulations that show promise in the dermatologic armamentarium. It is a great choice for use in a prep-procedure skin care regimen to speed healing. Use after a procedure is prohibited by the stinging associated with the low pH of properly formulated products.

References

2. Dermatol Surg. 2001 Feb;27(2):137-42.

3. J Invest Dermatol. 1994 Jan;102(1):122-4.

4. Dermatol Surg. 2005 Jul;31(7 Pt 2):814-7.

5. Annu Rev Nutr. 1994;14:371-91.

6. J Drugs Dermatol. 2008 Jul;7(7 Suppl):s2-6.

7. J Am Acad Dermatol. 2003 Jun;48(6):866-74.

8. J Invest Dermatol. 1994 Apr;102(4):470-5.

9. Free Radic Biol Med. 1997;23:85-91.

10. J Drugs Dermatol. 2014 Oct;13(10):1208-13.

11. J Am Acad Dermatol. 1996 Jan;34(1):29-33.

12. Dermatol Surg. 1998 Aug;24(8):849-56.

13. J Am Acad Dermatol. 2008 Sep;59(3):418-25.

14. J Biol Chem. 1983 Jun 10;258(11):6695-7.

15. J Phys Chem. 1983;87:1809-12.

16. Br J Dermatol. 1992 Sep;127(3):247-53.

17. J Invest Dermatol. 1991;96:587.

18. J Invest Dermatol. 2001 Jun;116(6):853-9.

19. Exp Dermatol. 2003 Jun;12(3):237-44.

20. J Drugs Dermatol. 2012 Jan;11(1):51-6.

21. Clin Cosmet Investig Dermatol. 2015 Sep 2;8:463-70

22. Int J Dermatol. 2004 Aug;43(8):604-7.

23. Dermatology. 2003;206(4):316-20.

24. Am J Clin Dermatol. 2011 Apr 1;12(2):87-99.

25. Phytother Res. 2006 Nov;20(11):921-34.

26. J Cutan Med Surg. 2009 Mar-Apr;13(2):74-81.

27. Lasers Med Sci. 2015 Jan;30(1):159-63.

28. Dermatol Surg. 1998 Mar;24(3):331-4.

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Leslie Baumann, MD

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Vitamin C (ascorbic acid) is one of the four most important ingredients in skin care products.

• It is proven to increase collagen production when applied topically to skin.

• It inhibits tyrosinase to even skin tone and has a strong antioxidant activity.

• It is absorbed well orally, but not enough gets to the skin.

• It is best absorbed at a pH of 2.0.

• It is unstable when exposed to light and air. Instruct patients to discard 6 months after opening.

Antioxidant and anti-aging activity

Skin lightening activity

Melasma

PIPA

Stretch marks

The depigmenting effects of vitamin C can lighten the pigmentation associated with stretch marks and its anti-inflammatory activity can contribute to blunting related redness.¹²

Conclusion

References

2. Dermatol Surg. 2001 Feb;27(2):137-42.

3. J Invest Dermatol. 1994 Jan;102(1):122-4.

4. Dermatol Surg. 2005 Jul;31(7 Pt 2):814-7.

5. Annu Rev Nutr. 1994;14:371-91.

6. J Drugs Dermatol. 2008 Jul;7(7 Suppl):s2-6.

7. J Am Acad Dermatol. 2003 Jun;48(6):866-74.

8. J Invest Dermatol. 1994 Apr;102(4):470-5.

9. Free Radic Biol Med. 1997;23:85-91.

10. J Drugs Dermatol. 2014 Oct;13(10):1208-13.

11. J Am Acad Dermatol. 1996 Jan;34(1):29-33.

12. Dermatol Surg. 1998 Aug;24(8):849-56.

13. J Am Acad Dermatol. 2008 Sep;59(3):418-25.

14. J Biol Chem. 1983 Jun 10;258(11):6695-7.

15. J Phys Chem. 1983;87:1809-12.

16. Br J Dermatol. 1992 Sep;127(3):247-53.

17. J Invest Dermatol. 1991;96:587.

18. J Invest Dermatol. 2001 Jun;116(6):853-9.

19. Exp Dermatol. 2003 Jun;12(3):237-44.

20. J Drugs Dermatol. 2012 Jan;11(1):51-6.

21. Clin Cosmet Investig Dermatol. 2015 Sep 2;8:463-70

22. Int J Dermatol. 2004 Aug;43(8):604-7.

23. Dermatology. 2003;206(4):316-20.

24. Am J Clin Dermatol. 2011 Apr 1;12(2):87-99.

25. Phytother Res. 2006 Nov;20(11):921-34.

26. J Cutan Med Surg. 2009 Mar-Apr;13(2):74-81.

27. Lasers Med Sci. 2015 Jan;30(1):159-63.

28. Dermatol Surg. 1998 Mar;24(3):331-4.

Vitamin C (ascorbic acid) is one of the four most important ingredients in skin care products.

• It is proven to increase collagen production when applied topically to skin.

• It inhibits tyrosinase to even skin tone and has a strong antioxidant activity.

• It is absorbed well orally, but not enough gets to the skin.

• It is best absorbed at a pH of 2.0.

• It is unstable when exposed to light and air. Instruct patients to discard 6 months after opening.

Antioxidant and anti-aging activity

Skin lightening activity

Melasma

PIPA

Stretch marks

The depigmenting effects of vitamin C can lighten the pigmentation associated with stretch marks and its anti-inflammatory activity can contribute to blunting related redness.¹²

Conclusion

References

1. J Biol Chem. 1994 May 6;269(18):13685-8.

2. Dermatol Surg. 2001 Feb;27(2):137-42.

3. J Invest Dermatol. 1994 Jan;102(1):122-4.

4. Dermatol Surg. 2005 Jul;31(7 Pt 2):814-7.

5. Annu Rev Nutr. 1994;14:371-91.

6. J Drugs Dermatol. 2008 Jul;7(7 Suppl):s2-6.

7. J Am Acad Dermatol. 2003 Jun;48(6):866-74.

8. J Invest Dermatol. 1994 Apr;102(4):470-5.

9. Free Radic Biol Med. 1997;23:85-91.

10. J Drugs Dermatol. 2014 Oct;13(10):1208-13.

11. J Am Acad Dermatol. 1996 Jan;34(1):29-33.

12. Dermatol Surg. 1998 Aug;24(8):849-56.

13. J Am Acad Dermatol. 2008 Sep;59(3):418-25.

14. J Biol Chem. 1983 Jun 10;258(11):6695-7.

15. J Phys Chem. 1983;87:1809-12.

16. Br J Dermatol. 1992 Sep;127(3):247-53.

17. J Invest Dermatol. 1991;96:587.

18. J Invest Dermatol. 2001 Jun;116(6):853-9.

19. Exp Dermatol. 2003 Jun;12(3):237-44.

20. J Drugs Dermatol. 2012 Jan;11(1):51-6.

21. Clin Cosmet Investig Dermatol. 2015 Sep 2;8:463-70

22. Int J Dermatol. 2004 Aug;43(8):604-7.

23. Dermatology. 2003;206(4):316-20.

24. Am J Clin Dermatol. 2011 Apr 1;12(2):87-99.

25. Phytother Res. 2006 Nov;20(11):921-34.

26. J Cutan Med Surg. 2009 Mar-Apr;13(2):74-81.

27. Lasers Med Sci. 2015 Jan;30(1):159-63.

28. Dermatol Surg. 1998 Mar;24(3):331-4.

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9. Crit Rev Microbiol. 2011;37(3):245-9.

Just as we learned early in life that 70% of the human body is composed of water, water covers approximately the same percentage of the earth’s surface. While fishing and harvesting of algae have occurred throughout human history,¹ it has only been since the 1970s that widespread scientific interest in the great biological and chemical diversity of the vast oceans of the world has led to investigations into medical and cosmetic applications of the rich life beneath the sea.² During this period, the marine environment has been found to boast multiple organisms with unique metabolisms adapted for survival in challenging conditions, yielding secondary metabolites, some of which have become valuable in the pharmaceutical and cosmeceutical markets.^3,4 Thus, the inclusion of bioactive substances from the sea in drugs and cosmetic products is primarily a recent phenomenon.¹ In fact, marine ingredients in cosmetics are thought to confer various benefits to skin health, including antioxidant, anti-acne, anti-wrinkle, and anti-tyrosinase activity.

Chemistry and biologic activity

Several marine microbial natural products have been found to display antimicrobial, antitumor, and anti-inflammatory activity.^2,5 And seaweed extracts (green, brown, and red algal compounds that include constituents such as phlorotannins, sulfated polysaccharides, and tyrosinase inhibitors) have been incorporated into cosmeceutical products, with a long history of traditional folk uses for various health – including skin – conditions.^3,6,7 Kim and Li reviewed the beneficial health effects of marine fungi-derived terpenoids in 2012, reporting that hundreds of these compounds have been discovered in the last few decades, with many exhibiting anti-inflammatory, anticancer, antimicrobial, and antioxidant activity.^8,9 Terpenoids, or isoprenoids, are a subclass of prenyllipids, which include prenylquinones, sterols, and terpenes, the largest class of natural substances.¹⁰

The terpenes are the largest group of biologically diverse marine compounds, and include the pseudopterosins, which are structurally discrete active metabolites of the Caribbean gorgonian soft coral Pseudopterogorgia elisabethae, which is native to the waters of the Caribbean Sea, Central Bahamas, Bermuda, the West Indies, and the Florida keys.^11,12 The most common gorgonian corals are diterpenes.¹³ Twenty-six derivatives of the octocoral P. elisabethae (designated PsA-PsZ), also known as the sea whip, sea fan, or sea plume, have been isolated.^11,12,14 Pseudopterosins were first isolated in 1986.^14,15

Based on the identified biologic activities, particularly anti-inflammatory capacity, of pseudopterosins, researchers have investigated their potential for treatment of various conditions including asthma, cancer, contact dermatitis, dermatoheliosis, HIV, photodamage, psoriasis, and rheumatoid arthritis.^1,11

After decades of extensive research of pseudopterosins, these tricyclic diterpene glycosides are thought to provide superior anti-inflammatory and analgesic properties, compared to standard anti-inflammatory treatments, without inducing adverse side effects; they also offer marked antimicrobial and wound-healing effects.^{3,11,14,16-19}

Other marine diterpene glycosides include eleutherobins and fucosides, which also exhibit notable biologic activity.¹⁵ In particular, the anti-inflammatory and analgesic activities of pseudopterosins have been found to be concentration- and dose-dependently more potent than the standard-bearing indomethacin.^11,14,17

Marine ingredients in topical formulations

The first product to include pseudopterosins was the skin formulation Resilience marketed by Estée Lauder over a decade ago.^19,20 Natural marine ingredients have since been incorporated into a few more products, such as Imedeen, an oral skin care preparation that contains Marine Complex.²¹

In 2012, Rietveld et al. ascertained whether the Marine Complex from Imedeen could variously alter skin morphogenesis in female and male human skin equivalents. Cells were culled from female and male donors between the ages of 30 and 45 years for human skin equivalents that were cultured for 7 or 11 weeks with or without Marine Complex. The investigators found that the number of Ki67-positive epidermal cells was greatly augmented by Marine Complex in female human skin equivalents. The Marine Complex significantly spurred the level of secreted pro-collagen I and elevated the deposition of laminin 332 and collagen type VII in the dermis. Human skin equivalents treated with Marine Complex also exhibited more viable epidermal cell layers and a thicker dermal extracellular matrix, compared to controls, with these effects less salient in male human skin equivalents. The investigators concluded that supplementation with Marine Complex positively stimulated overall human skin equivalent tissue formation, with its effects on the basement membrane and dermal constituents suggestive of potential for use against human skin aging.²¹

Previously, Xhauflaire-Uhoda et al. evaluated the skin hydrating and firming dose-response effects of cosmetic preparations enriched in algae- and fish collagen–derived substances in randomized controlled double-blind medium-term (12 subjects aged 18-55 years) and short-term (3 subjects over the age of 50) trials. In the short term, serum formulations enriched in marine compounds manifested a superior moisturizing effect on the forearm compared with creams. In later stages, cream formulations were more active, especially after repeated applications. Investigators observed a sustained firming activity in association with both the lotion and cream during treatment, but such results did not persist after treatment was stopped.²²

Product development

Technological advances, including sampling strategies, nanoscale nuclear magnetic resonance for structure determination, total chemical synthesis, fermentation, exploration of genomic and metagenomic resources, combinatorial biosynthesis, synthetic biology, and biotechnology represent important ways in which novel marine natural products are being developed, according to several authors.^1,2,4

Conclusion

Marine ingredients are a relatively new and fascinating category of substances that can and are being harnessed for pharmaceutical, cosmeceutical, cosmetic, and nutritional uses. Beyond the challenges of obtaining sufficient raw materials and producing effective formulations, the continued viability of such resources may be threatened by human exploitation of the seas and climate change. That said, the oceans offer the greatest biodiversity on the planet and dermatologic preparations derived from such sources present intriguing possibilities, particularly the apparent anti-inflammatory activity of gorgonian and other terpenes. These compounds appear to have the potential to replace, or serve as desirable alternatives to, conventional therapies for inflammatory skin disorders.

References

1. Biotechnol Adv. 2011;29(5):468-82.

2. Mar Drugs. 2013;11(3):700-17.

3. Mar Drugs. 2014;12(2):1066-101.

4. Future Med Chem. 2011;3(12):1475-89.

5. Org Lett. 2000;2(4):507-10.

6. Mar Drugs. 2013;11(1):146-64.

7. J Cosmet Dermatol. 2014;13(1):56-67.

8. Adv Food Nutr Res. 2012;65:409-13.

10. Nat Chem Biol. 2007;3(7):408-14.

11. J Drugs Dermatol. 2013;12(10):1177-9.

12. J Ind Microbiol Biotechnol. 2006;33(7):532-8.

13. Nat Prod Rep. 2009;26(5):681-710.

14. Proc Natl Acad Sci USA. 1986;83(17):6238-40.

15. Bioorg Med Chem. 2011;19(22):6702-19.

16. Arch Biochem Biophys. 2004;424(1):97-104.

17. Asia Pac J Clin Nutr. 2006;15(2):143-52.

18. J Nat Prod. 2004;67(10):1672-80.

19. Mar Drugs. 2004 May;2:73-82.

20. J Nat Prod. 2004;67(8):1216-38.

21. J Cosmet Dermatol. 2012;11(3):213-22.

22. Int J Cosmet Sci. 2008;30(2):131-8.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook, “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.

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9. Crit Rev Microbiol. 2011;37(3):245-9.

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Chemistry and biologic activity

Marine ingredients in topical formulations

Product development

Conclusion

References

1. Biotechnol Adv. 2011;29(5):468-82.

2. Mar Drugs. 2013;11(3):700-17.

3. Mar Drugs. 2014;12(2):1066-101.

4. Future Med Chem. 2011;3(12):1475-89.

5. Org Lett. 2000;2(4):507-10.

6. Mar Drugs. 2013;11(1):146-64.

7. J Cosmet Dermatol. 2014;13(1):56-67.

8. Adv Food Nutr Res. 2012;65:409-13.

10. Nat Chem Biol. 2007;3(7):408-14.

11. J Drugs Dermatol. 2013;12(10):1177-9.

12. J Ind Microbiol Biotechnol. 2006;33(7):532-8.

13. Nat Prod Rep. 2009;26(5):681-710.

14. Proc Natl Acad Sci USA. 1986;83(17):6238-40.

15. Bioorg Med Chem. 2011;19(22):6702-19.

16. Arch Biochem Biophys. 2004;424(1):97-104.

17. Asia Pac J Clin Nutr. 2006;15(2):143-52.

18. J Nat Prod. 2004;67(10):1672-80.

19. Mar Drugs. 2004 May;2:73-82.

20. J Nat Prod. 2004;67(8):1216-38.

21. J Cosmet Dermatol. 2012;11(3):213-22.

22. Int J Cosmet Sci. 2008;30(2):131-8.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook, “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.

Chemistry and biologic activity

Marine ingredients in topical formulations

Product development

Conclusion

References

1. Biotechnol Adv. 2011;29(5):468-82.

2. Mar Drugs. 2013;11(3):700-17.

3. Mar Drugs. 2014;12(2):1066-101.

4. Future Med Chem. 2011;3(12):1475-89.

5. Org Lett. 2000;2(4):507-10.

6. Mar Drugs. 2013;11(1):146-64.

7. J Cosmet Dermatol. 2014;13(1):56-67.

8. Adv Food Nutr Res. 2012;65:409-13.

9. Crit Rev Microbiol. 2011;37(3):245-9.

10. Nat Chem Biol. 2007;3(7):408-14.

11. J Drugs Dermatol. 2013;12(10):1177-9.

12. J Ind Microbiol Biotechnol. 2006;33(7):532-8.

13. Nat Prod Rep. 2009;26(5):681-710.

14. Proc Natl Acad Sci USA. 1986;83(17):6238-40.

15. Bioorg Med Chem. 2011;19(22):6702-19.

16. Arch Biochem Biophys. 2004;424(1):97-104.

17. Asia Pac J Clin Nutr. 2006;15(2):143-52.

18. J Nat Prod. 2004;67(10):1672-80.

19. Mar Drugs. 2004 May;2:73-82.

20. J Nat Prod. 2004;67(8):1216-38.

21. J Cosmet Dermatol. 2012;11(3):213-22.

22. Int J Cosmet Sci. 2008;30(2):131-8.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook, “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.

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