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Vaccinium myrtillus (bilberry seed oil) extract
A member of the Ericaceae family, bilberry (Vaccinium myrtillus) is native to northern Europe and North America, and its fruit is known to contain myriad polyphenols that display potent antioxidant and anti-inflammatory activity.1,2 Also known as European blueberry or whortleberry, this perennial deciduous shrub is also one of the richest sources of the polyphenolic pigments anthocyanins.3-5 Indeed, anthocyanins impart the blue/black color to bilberries and other berries and are thought to be the primary bioactive constituents of berries associated with numerous health benefits.3,6 They are also known to confer anti-allergic, anticancer, and wound healing activity.4 Overall, bilberry has also been reported to exert anti-inflammatory, lipid-lowering, and antimicrobial activity.3 In this column, the focus will be on the chemical constituents and properties of V. myrtillus that indicate potential or applicability for skin care.
Active ingredients of bilberry
Bilberry seed oil contains unsaturated fatty acids such as linoleic acid and alpha-linolenic acid, which exhibit anti-inflammatory activity and contribute to the suppression of tyrosinase. For instance, Ando et al. showed, in 1998, that linoleic and alpha-linolenic acids lighten UV-induced skin hyperpigmentation. Their in vitro experiments using cultured murine melanoma cells and in vivo study of the topical application of either acid to the UV-induced hyperpigmented dorsal skin of guinea pigs revealed pigment-lightening effects that they partly ascribed to inhibited melanin synthesis by active melanocytes and accelerated desquamation of epidermal melanin pigment.7
A 2009 comparative study of the anthocyanin composition as well as antimicrobial and antioxidant activities delivered by bilberry and blueberry fruits and their skins by Burdulis et al. revealed robust functions in both fruits. Cyanidin was found to be an active anthocyanidin in bilberry. Cultivars of both fruits demonstrated antimicrobial and antioxidant activity, with bilberry fruit skin demonstrating potent antiradical activity.8
The anthocyanins of V. myrtillus are reputed to impart protection against cardiovascular disorders, age-induced oxidative stress, inflammatory responses, and various degenerative conditions, as well ameliorate neuronal and cognitive brain functions and ocular health.6
In 2012, Bornsek et al. demonstrated that bilberry (and blueberry) anthocyanins function as potent intracellular antioxidants, which may account for their noted health benefits despite relatively low bioavailability.9
Six years later, a chemical composition study of wild bilberry found in Montenegro, Brasanac-Vukanovic et al. determined that chlorogenic acid was the most prevalent phenolic constituent, followed by protocatechuic acid, with resveratrol, isoquercetin, quercetin, and hyperoside also found to be abundant. In vitro assays indicated significant antioxidant activity exhibited by these compounds.10
Activity against allergic contact dermatitis
Yamaura et al. used a mouse model, in 2011, to determine that the anthocyanins from a bilberry extract attenuated various symptoms of chronic allergic contact dermatitis, particularly alleviating pruritus.8 A year later, Yamaura et al. used a BALB/c mouse model of allergic contact dermatitis to compare the antipruritic effect of anthocyanin-rich quality-controlled bilberry extract and anthocyanidin-rich degraded extract. The investigators found that anthocyanins, but not anthocyanidins, derived from bilberry exert an antipruritic effect, likely through their inhibitory action on mast cell degranulation. They concluded that anthocyanin-rich bilberry extract could act as an effective oral supplement to treat pruritic symptoms of skin disorders such as chronic allergic contact dermatitis and atopic dermatitis.11
Antioxidant and anti-inflammatory activity
Bilberries, consumed since ancient times, are reputed to function as potent antioxidants because of a wide array of phenolic constituents, and this fruit is gaining interest for use in pharmaceuticals.12
In 2008, Svobodová et al. assessed possible UVA preventive properties of V. myrtillus fruit extract in a human keratinocyte cell line (HaCaT), finding that pre- or posttreatment mitigated UVA-induced harm. They also observed a significant decrease in UVA-caused reactive oxygen species (ROS) formation and the prevention or attenuation of UVA-stimulated peroxidation of membrane lipids. Intracellular glutathione was also protected. The investigators attributed the array of cytoprotective effects conferred by V. myrtillus extract primarily to its constituent anthocyanins.2 A year later, they found that the phenolic fraction of V. myrtillus fruits inhibited UVB-induced damage to HaCaT keratinocytes in vitro.13
In 2014, Calò and Marabini used HaCaT keratinocytes to ascertain whether a water-soluble V. myrtillus extract could mitigate UVA- and UVB-induced damage. They found that the extract diminished UVB-induced cytotoxicity and genotoxicity at lower doses, decreasing lipid peroxidation but exerting no effect on reactive oxygen species generated by UVB. The extract attenuated genotoxicity induced by UVA as well as ROS and apoptosis. Overall, the investigators concluded that V. myrtillus extract demonstrated antioxidant activity, particularly against UVA exposure.14
Four years later, Bucci et al. developed nanoberries, an ultradeformable liposome carrying V. myrtillus ethanolic extract, and determined that the preparation could penetrate the stratum corneum safely and suggested potential for yielding protection against photodamage.15
Skin preparations
In 2021, Tadic et al. developed an oil-in-water (O/W) cream containing wild bilberry leaf extracts and seed oil. The leaves contained copious phenolic acids (particularly chlorogenic acid), flavonoids (especially isoquercetin), and resveratrol. The seed oil was rife with alpha-linolenic, linoleic, and oleic acids. The investigators conducted an in vivo study over 30 days in 25 healthy volunteers (20 women, 5 men; mean age 23.36 ± 0.64 years). They found that the O/W cream successfully increased stratum corneum hydration, enhanced skin barrier function, and maintained skin pH after topical application. The cream was also well tolerated. In vitro assays also indicated that the bilberry isolates displayed notable antioxidant capacity (stronger in the case of the leaves). Tadic et al. suggested that skin disorders characterized by oxidative stress and/or xerosis may be appropriate targets for topically applied bilberry cream.1
Early in 2022, Ruscinc et al. reported on their efforts to incorporate V. myrtillus extract into a multifunctional sunscreen. In vitro and in vivo tests revealed that while sun protection factor was lowered in the presence of the extract, the samples were safe and photostable. The researchers concluded that further study is necessary to elucidate the effect of V. myrtillus extract on photoprotection.16
V. myrtillus has been consumed by human beings for many generations. Skin care formulations based on this ingredient have not been associated with adverse events. Notably, the Environmental Working Group has rated V. myrtillus (bilberry seed) oil as very safe.17
Summary
While research, particularly in the form of randomized controlled trials, is called for, because the fatty acids it contains have been shown to suppress tyrosinase. Currently, this botanical agent seems to be most suited for sensitive, aging skin and for skin with an uneven tone, particularly postinflammatory pigmentation and melasma.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur in Miami. She founded the division of cosmetic dermatology at the University of Miami in 1997. The third edition of her bestselling textbook, “Cosmetic Dermatology,” was published in 2022. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Johnson & Johnson, and Burt’s Bees. She is the CEO of Skin Type Solutions, an SaaS company used to generate skin care routines in office and as an ecommerce solution. Write to her at dermnews@mdedge.com.
References
1. Tadic VM et al. Antioxidants (Basel). 2021 Mar 16;10(3):465.
2. Svobodová A et al. Biofactors. 2008;33(4):249-66.
3. Chu WK et al. Bilberry (Vaccinium myrtillus L.), in Benzie IFF, Wachtel-Galor S, eds., “Herbal Medicine: Biomolecular and Clinical Aspects,” 2nd ed. (Boca Raton, Fla.: CRC Press/Taylor & Francis, 2011, Chapter 4).
4. Yamaura K et al. Pharmacognosy Res. 2011 Jul;3(3):173-7.
5. Stefanescu BE et al. Molecules. 2019 May 29;24(11):2046.
6. Smeriglio A et al. Mini Rev Med Chem. 2014;14(7):567-84.
7. Ando H et al. Arch Dermatol Res. 1998 Jul;290(7):375-81.
8. Burdulis D et al. Acta Pol Pharm. 2009 Jul-Aug;66(4):399-408.
9. Bornsek SM et al. Food Chem. 2012 Oct 15;134(4):1878-84.
10. Brasanac-Vukanovic S et al. Molecules. 2018 Jul 26;23(8):1864.
11. Yamaura K et al. J Food Sci. 2012 Dec;77(12):H262-7.
12. Pires TCSP et al. Curr Pharm Des. 2020;26(16):1917-28.
13. Svobodová A et al. J Dermatol Sci. 2009 Dec;56(3):196-204.
14. Calò R, Marabini L. J Photochem Photobiol B. 2014 Mar 5;132:27-35.
15. Bucci P et al. J Cosmet Dermatol. 2018 Oct;17(5):889-99.
16. Ruscinc N et al. J Cosmet Dermatol. 2022 Jan 13.
17. Environmental Working Group’s Skin Deep website. Vaccinium Myrtillus Bilberry Seed Oil. Accessed October 18, 2022.
A member of the Ericaceae family, bilberry (Vaccinium myrtillus) is native to northern Europe and North America, and its fruit is known to contain myriad polyphenols that display potent antioxidant and anti-inflammatory activity.1,2 Also known as European blueberry or whortleberry, this perennial deciduous shrub is also one of the richest sources of the polyphenolic pigments anthocyanins.3-5 Indeed, anthocyanins impart the blue/black color to bilberries and other berries and are thought to be the primary bioactive constituents of berries associated with numerous health benefits.3,6 They are also known to confer anti-allergic, anticancer, and wound healing activity.4 Overall, bilberry has also been reported to exert anti-inflammatory, lipid-lowering, and antimicrobial activity.3 In this column, the focus will be on the chemical constituents and properties of V. myrtillus that indicate potential or applicability for skin care.
Active ingredients of bilberry
Bilberry seed oil contains unsaturated fatty acids such as linoleic acid and alpha-linolenic acid, which exhibit anti-inflammatory activity and contribute to the suppression of tyrosinase. For instance, Ando et al. showed, in 1998, that linoleic and alpha-linolenic acids lighten UV-induced skin hyperpigmentation. Their in vitro experiments using cultured murine melanoma cells and in vivo study of the topical application of either acid to the UV-induced hyperpigmented dorsal skin of guinea pigs revealed pigment-lightening effects that they partly ascribed to inhibited melanin synthesis by active melanocytes and accelerated desquamation of epidermal melanin pigment.7
A 2009 comparative study of the anthocyanin composition as well as antimicrobial and antioxidant activities delivered by bilberry and blueberry fruits and their skins by Burdulis et al. revealed robust functions in both fruits. Cyanidin was found to be an active anthocyanidin in bilberry. Cultivars of both fruits demonstrated antimicrobial and antioxidant activity, with bilberry fruit skin demonstrating potent antiradical activity.8
The anthocyanins of V. myrtillus are reputed to impart protection against cardiovascular disorders, age-induced oxidative stress, inflammatory responses, and various degenerative conditions, as well ameliorate neuronal and cognitive brain functions and ocular health.6
In 2012, Bornsek et al. demonstrated that bilberry (and blueberry) anthocyanins function as potent intracellular antioxidants, which may account for their noted health benefits despite relatively low bioavailability.9
Six years later, a chemical composition study of wild bilberry found in Montenegro, Brasanac-Vukanovic et al. determined that chlorogenic acid was the most prevalent phenolic constituent, followed by protocatechuic acid, with resveratrol, isoquercetin, quercetin, and hyperoside also found to be abundant. In vitro assays indicated significant antioxidant activity exhibited by these compounds.10
Activity against allergic contact dermatitis
Yamaura et al. used a mouse model, in 2011, to determine that the anthocyanins from a bilberry extract attenuated various symptoms of chronic allergic contact dermatitis, particularly alleviating pruritus.8 A year later, Yamaura et al. used a BALB/c mouse model of allergic contact dermatitis to compare the antipruritic effect of anthocyanin-rich quality-controlled bilberry extract and anthocyanidin-rich degraded extract. The investigators found that anthocyanins, but not anthocyanidins, derived from bilberry exert an antipruritic effect, likely through their inhibitory action on mast cell degranulation. They concluded that anthocyanin-rich bilberry extract could act as an effective oral supplement to treat pruritic symptoms of skin disorders such as chronic allergic contact dermatitis and atopic dermatitis.11
Antioxidant and anti-inflammatory activity
Bilberries, consumed since ancient times, are reputed to function as potent antioxidants because of a wide array of phenolic constituents, and this fruit is gaining interest for use in pharmaceuticals.12
In 2008, Svobodová et al. assessed possible UVA preventive properties of V. myrtillus fruit extract in a human keratinocyte cell line (HaCaT), finding that pre- or posttreatment mitigated UVA-induced harm. They also observed a significant decrease in UVA-caused reactive oxygen species (ROS) formation and the prevention or attenuation of UVA-stimulated peroxidation of membrane lipids. Intracellular glutathione was also protected. The investigators attributed the array of cytoprotective effects conferred by V. myrtillus extract primarily to its constituent anthocyanins.2 A year later, they found that the phenolic fraction of V. myrtillus fruits inhibited UVB-induced damage to HaCaT keratinocytes in vitro.13
In 2014, Calò and Marabini used HaCaT keratinocytes to ascertain whether a water-soluble V. myrtillus extract could mitigate UVA- and UVB-induced damage. They found that the extract diminished UVB-induced cytotoxicity and genotoxicity at lower doses, decreasing lipid peroxidation but exerting no effect on reactive oxygen species generated by UVB. The extract attenuated genotoxicity induced by UVA as well as ROS and apoptosis. Overall, the investigators concluded that V. myrtillus extract demonstrated antioxidant activity, particularly against UVA exposure.14
Four years later, Bucci et al. developed nanoberries, an ultradeformable liposome carrying V. myrtillus ethanolic extract, and determined that the preparation could penetrate the stratum corneum safely and suggested potential for yielding protection against photodamage.15
Skin preparations
In 2021, Tadic et al. developed an oil-in-water (O/W) cream containing wild bilberry leaf extracts and seed oil. The leaves contained copious phenolic acids (particularly chlorogenic acid), flavonoids (especially isoquercetin), and resveratrol. The seed oil was rife with alpha-linolenic, linoleic, and oleic acids. The investigators conducted an in vivo study over 30 days in 25 healthy volunteers (20 women, 5 men; mean age 23.36 ± 0.64 years). They found that the O/W cream successfully increased stratum corneum hydration, enhanced skin barrier function, and maintained skin pH after topical application. The cream was also well tolerated. In vitro assays also indicated that the bilberry isolates displayed notable antioxidant capacity (stronger in the case of the leaves). Tadic et al. suggested that skin disorders characterized by oxidative stress and/or xerosis may be appropriate targets for topically applied bilberry cream.1
Early in 2022, Ruscinc et al. reported on their efforts to incorporate V. myrtillus extract into a multifunctional sunscreen. In vitro and in vivo tests revealed that while sun protection factor was lowered in the presence of the extract, the samples were safe and photostable. The researchers concluded that further study is necessary to elucidate the effect of V. myrtillus extract on photoprotection.16
V. myrtillus has been consumed by human beings for many generations. Skin care formulations based on this ingredient have not been associated with adverse events. Notably, the Environmental Working Group has rated V. myrtillus (bilberry seed) oil as very safe.17
Summary
While research, particularly in the form of randomized controlled trials, is called for, because the fatty acids it contains have been shown to suppress tyrosinase. Currently, this botanical agent seems to be most suited for sensitive, aging skin and for skin with an uneven tone, particularly postinflammatory pigmentation and melasma.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur in Miami. She founded the division of cosmetic dermatology at the University of Miami in 1997. The third edition of her bestselling textbook, “Cosmetic Dermatology,” was published in 2022. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Johnson & Johnson, and Burt’s Bees. She is the CEO of Skin Type Solutions, an SaaS company used to generate skin care routines in office and as an ecommerce solution. Write to her at dermnews@mdedge.com.
References
1. Tadic VM et al. Antioxidants (Basel). 2021 Mar 16;10(3):465.
2. Svobodová A et al. Biofactors. 2008;33(4):249-66.
3. Chu WK et al. Bilberry (Vaccinium myrtillus L.), in Benzie IFF, Wachtel-Galor S, eds., “Herbal Medicine: Biomolecular and Clinical Aspects,” 2nd ed. (Boca Raton, Fla.: CRC Press/Taylor & Francis, 2011, Chapter 4).
4. Yamaura K et al. Pharmacognosy Res. 2011 Jul;3(3):173-7.
5. Stefanescu BE et al. Molecules. 2019 May 29;24(11):2046.
6. Smeriglio A et al. Mini Rev Med Chem. 2014;14(7):567-84.
7. Ando H et al. Arch Dermatol Res. 1998 Jul;290(7):375-81.
8. Burdulis D et al. Acta Pol Pharm. 2009 Jul-Aug;66(4):399-408.
9. Bornsek SM et al. Food Chem. 2012 Oct 15;134(4):1878-84.
10. Brasanac-Vukanovic S et al. Molecules. 2018 Jul 26;23(8):1864.
11. Yamaura K et al. J Food Sci. 2012 Dec;77(12):H262-7.
12. Pires TCSP et al. Curr Pharm Des. 2020;26(16):1917-28.
13. Svobodová A et al. J Dermatol Sci. 2009 Dec;56(3):196-204.
14. Calò R, Marabini L. J Photochem Photobiol B. 2014 Mar 5;132:27-35.
15. Bucci P et al. J Cosmet Dermatol. 2018 Oct;17(5):889-99.
16. Ruscinc N et al. J Cosmet Dermatol. 2022 Jan 13.
17. Environmental Working Group’s Skin Deep website. Vaccinium Myrtillus Bilberry Seed Oil. Accessed October 18, 2022.
A member of the Ericaceae family, bilberry (Vaccinium myrtillus) is native to northern Europe and North America, and its fruit is known to contain myriad polyphenols that display potent antioxidant and anti-inflammatory activity.1,2 Also known as European blueberry or whortleberry, this perennial deciduous shrub is also one of the richest sources of the polyphenolic pigments anthocyanins.3-5 Indeed, anthocyanins impart the blue/black color to bilberries and other berries and are thought to be the primary bioactive constituents of berries associated with numerous health benefits.3,6 They are also known to confer anti-allergic, anticancer, and wound healing activity.4 Overall, bilberry has also been reported to exert anti-inflammatory, lipid-lowering, and antimicrobial activity.3 In this column, the focus will be on the chemical constituents and properties of V. myrtillus that indicate potential or applicability for skin care.
Active ingredients of bilberry
Bilberry seed oil contains unsaturated fatty acids such as linoleic acid and alpha-linolenic acid, which exhibit anti-inflammatory activity and contribute to the suppression of tyrosinase. For instance, Ando et al. showed, in 1998, that linoleic and alpha-linolenic acids lighten UV-induced skin hyperpigmentation. Their in vitro experiments using cultured murine melanoma cells and in vivo study of the topical application of either acid to the UV-induced hyperpigmented dorsal skin of guinea pigs revealed pigment-lightening effects that they partly ascribed to inhibited melanin synthesis by active melanocytes and accelerated desquamation of epidermal melanin pigment.7
A 2009 comparative study of the anthocyanin composition as well as antimicrobial and antioxidant activities delivered by bilberry and blueberry fruits and their skins by Burdulis et al. revealed robust functions in both fruits. Cyanidin was found to be an active anthocyanidin in bilberry. Cultivars of both fruits demonstrated antimicrobial and antioxidant activity, with bilberry fruit skin demonstrating potent antiradical activity.8
The anthocyanins of V. myrtillus are reputed to impart protection against cardiovascular disorders, age-induced oxidative stress, inflammatory responses, and various degenerative conditions, as well ameliorate neuronal and cognitive brain functions and ocular health.6
In 2012, Bornsek et al. demonstrated that bilberry (and blueberry) anthocyanins function as potent intracellular antioxidants, which may account for their noted health benefits despite relatively low bioavailability.9
Six years later, a chemical composition study of wild bilberry found in Montenegro, Brasanac-Vukanovic et al. determined that chlorogenic acid was the most prevalent phenolic constituent, followed by protocatechuic acid, with resveratrol, isoquercetin, quercetin, and hyperoside also found to be abundant. In vitro assays indicated significant antioxidant activity exhibited by these compounds.10
Activity against allergic contact dermatitis
Yamaura et al. used a mouse model, in 2011, to determine that the anthocyanins from a bilberry extract attenuated various symptoms of chronic allergic contact dermatitis, particularly alleviating pruritus.8 A year later, Yamaura et al. used a BALB/c mouse model of allergic contact dermatitis to compare the antipruritic effect of anthocyanin-rich quality-controlled bilberry extract and anthocyanidin-rich degraded extract. The investigators found that anthocyanins, but not anthocyanidins, derived from bilberry exert an antipruritic effect, likely through their inhibitory action on mast cell degranulation. They concluded that anthocyanin-rich bilberry extract could act as an effective oral supplement to treat pruritic symptoms of skin disorders such as chronic allergic contact dermatitis and atopic dermatitis.11
Antioxidant and anti-inflammatory activity
Bilberries, consumed since ancient times, are reputed to function as potent antioxidants because of a wide array of phenolic constituents, and this fruit is gaining interest for use in pharmaceuticals.12
In 2008, Svobodová et al. assessed possible UVA preventive properties of V. myrtillus fruit extract in a human keratinocyte cell line (HaCaT), finding that pre- or posttreatment mitigated UVA-induced harm. They also observed a significant decrease in UVA-caused reactive oxygen species (ROS) formation and the prevention or attenuation of UVA-stimulated peroxidation of membrane lipids. Intracellular glutathione was also protected. The investigators attributed the array of cytoprotective effects conferred by V. myrtillus extract primarily to its constituent anthocyanins.2 A year later, they found that the phenolic fraction of V. myrtillus fruits inhibited UVB-induced damage to HaCaT keratinocytes in vitro.13
In 2014, Calò and Marabini used HaCaT keratinocytes to ascertain whether a water-soluble V. myrtillus extract could mitigate UVA- and UVB-induced damage. They found that the extract diminished UVB-induced cytotoxicity and genotoxicity at lower doses, decreasing lipid peroxidation but exerting no effect on reactive oxygen species generated by UVB. The extract attenuated genotoxicity induced by UVA as well as ROS and apoptosis. Overall, the investigators concluded that V. myrtillus extract demonstrated antioxidant activity, particularly against UVA exposure.14
Four years later, Bucci et al. developed nanoberries, an ultradeformable liposome carrying V. myrtillus ethanolic extract, and determined that the preparation could penetrate the stratum corneum safely and suggested potential for yielding protection against photodamage.15
Skin preparations
In 2021, Tadic et al. developed an oil-in-water (O/W) cream containing wild bilberry leaf extracts and seed oil. The leaves contained copious phenolic acids (particularly chlorogenic acid), flavonoids (especially isoquercetin), and resveratrol. The seed oil was rife with alpha-linolenic, linoleic, and oleic acids. The investigators conducted an in vivo study over 30 days in 25 healthy volunteers (20 women, 5 men; mean age 23.36 ± 0.64 years). They found that the O/W cream successfully increased stratum corneum hydration, enhanced skin barrier function, and maintained skin pH after topical application. The cream was also well tolerated. In vitro assays also indicated that the bilberry isolates displayed notable antioxidant capacity (stronger in the case of the leaves). Tadic et al. suggested that skin disorders characterized by oxidative stress and/or xerosis may be appropriate targets for topically applied bilberry cream.1
Early in 2022, Ruscinc et al. reported on their efforts to incorporate V. myrtillus extract into a multifunctional sunscreen. In vitro and in vivo tests revealed that while sun protection factor was lowered in the presence of the extract, the samples were safe and photostable. The researchers concluded that further study is necessary to elucidate the effect of V. myrtillus extract on photoprotection.16
V. myrtillus has been consumed by human beings for many generations. Skin care formulations based on this ingredient have not been associated with adverse events. Notably, the Environmental Working Group has rated V. myrtillus (bilberry seed) oil as very safe.17
Summary
While research, particularly in the form of randomized controlled trials, is called for, because the fatty acids it contains have been shown to suppress tyrosinase. Currently, this botanical agent seems to be most suited for sensitive, aging skin and for skin with an uneven tone, particularly postinflammatory pigmentation and melasma.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur in Miami. She founded the division of cosmetic dermatology at the University of Miami in 1997. The third edition of her bestselling textbook, “Cosmetic Dermatology,” was published in 2022. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Johnson & Johnson, and Burt’s Bees. She is the CEO of Skin Type Solutions, an SaaS company used to generate skin care routines in office and as an ecommerce solution. Write to her at dermnews@mdedge.com.
References
1. Tadic VM et al. Antioxidants (Basel). 2021 Mar 16;10(3):465.
2. Svobodová A et al. Biofactors. 2008;33(4):249-66.
3. Chu WK et al. Bilberry (Vaccinium myrtillus L.), in Benzie IFF, Wachtel-Galor S, eds., “Herbal Medicine: Biomolecular and Clinical Aspects,” 2nd ed. (Boca Raton, Fla.: CRC Press/Taylor & Francis, 2011, Chapter 4).
4. Yamaura K et al. Pharmacognosy Res. 2011 Jul;3(3):173-7.
5. Stefanescu BE et al. Molecules. 2019 May 29;24(11):2046.
6. Smeriglio A et al. Mini Rev Med Chem. 2014;14(7):567-84.
7. Ando H et al. Arch Dermatol Res. 1998 Jul;290(7):375-81.
8. Burdulis D et al. Acta Pol Pharm. 2009 Jul-Aug;66(4):399-408.
9. Bornsek SM et al. Food Chem. 2012 Oct 15;134(4):1878-84.
10. Brasanac-Vukanovic S et al. Molecules. 2018 Jul 26;23(8):1864.
11. Yamaura K et al. J Food Sci. 2012 Dec;77(12):H262-7.
12. Pires TCSP et al. Curr Pharm Des. 2020;26(16):1917-28.
13. Svobodová A et al. J Dermatol Sci. 2009 Dec;56(3):196-204.
14. Calò R, Marabini L. J Photochem Photobiol B. 2014 Mar 5;132:27-35.
15. Bucci P et al. J Cosmet Dermatol. 2018 Oct;17(5):889-99.
16. Ruscinc N et al. J Cosmet Dermatol. 2022 Jan 13.
17. Environmental Working Group’s Skin Deep website. Vaccinium Myrtillus Bilberry Seed Oil. Accessed October 18, 2022.
Artemisia capillaris extract
Melasma is a difficult disorder to treat. With the removal of hydroquinone from the cosmetic market and the prevalence of dyschromia, new skin lightening ingredients are being sought and many new discoveries are coming from Asia.
There are more than 500 species of the genus Artemisia (of the Astraceae or Compositae family) dispersed throughout the temperate areas of Asia, Europe, and North America.1 Various parts of the shrub Artemisia capillaris, found abundantly in China, Japan, and Korea, have been used in traditional medicine in Asia for hundreds of years. A. capillaris (Yin-Chen in Chinese) has been deployed in traditional Chinese medicine as a diuretic, to protect the liver, and to treat skin inflammation.2,3 Antioxidant, anti-inflammatory, antisteatotic, antitumor, and antiviral properties have been associated with this plant,3 and hydrating effects have been recently attributed to it. In Korean medicine, A. capillaris (InJin in Korean) has been used for its hepatoprotective, analgesic, and antipyretic activities.4,5 In this column, the focus will be on recent evidence that suggests possible applications in skin care.
Chemical constituents
In 2008, Kim et al. studied the anticarcinogenic activity of A. capillaris, among other medicinal herbs, using the 7,12-dimethylbenz[a]anthracene (DMBA)-induced mouse skin carcinogenesis model. The researchers found that A. capillaris exhibited the most effective anticarcinogenic activity compared to the other herbs tested, with such properties ascribed to its constituent camphor, 1-borneol, coumarin, and achillin. Notably, the chloroform fraction of A. capillaris significantly lowered the number of tumors/mouse and tumor incidence compared with the other tested herbs.6
The wide range of biological functions associated with A. capillaris, including anti-inflammatory, antioxidant, antidiabetic, antisteatotic, and antitumor activities have, in various studies, been attributed to the bioactive constituents scoparone, scopoletin, capillarisin, capillin, and chlorogenic acids.3
Tyrosinase-related protein 1 (TYRP-1) and its role in skin pigmentation
Tyrosinase related protein 1 (TYRP-1) is structurally similar to tyrosinase, but its role is still being elucidated. Mutations in TYR-1 results in oculocutaneous albinism. TYRP-1 is involved in eumelanin synthesis, but not in pheomelanin synthesis. Mutations in TYRP-1 affect the quality of melanin synthesized rather than the quantity.4 TYRP-1 is being looked at as a target for treatment of hyperpigmentation disorders such as melasma.
Effects on melanin synthesis
A. capillaris reduces the expression of TYRP-1, making it attractive for use in skin lightening products. Although there are not a lot of data, this is a developing area of interest and the following will discuss what is known so far.
Kim et al. investigated the antimelanogenic activity of 10 essential oils, including A. capillaris, utilizing the B16F10 cell line model. A. capillaris was among four extracts found to hinder melanogenesis, and the only one that improved cell proliferation, displayed anti-H2O2 activity, and reduced tyrosinase-related protein (TRP)-1 expression. The researchers determined that A. capillaris extract suppressed melanin production through the downregulation of the TRP 1 translational level. They concluded that while investigations using in vivo models are necessary to buttress and validate these results, A. capillaris extract appears to be suitable as a natural therapeutic antimelanogenic agent as well as a skin-whitening ingredient in cosmeceutical products.7
Tabassum et al. screened A. capillaris for antipigmentary functions using murine cultured cells (B16-F10 malignant melanocytes). They found that the A. capillaris constituent 4,5-O-dicaffeoylquinic acid significantly and dose-dependently diminished melanin production and tyrosinase activity in the melanocytes. The expression of tyrosinase-related protein-1 was also decreased. Further, the researchers observed antipigmentary activity in a zebrafish model, with no toxicity demonstrated by either A. capillaris or its component 4,5-O-dicaffeoylquinic acid. They concluded that this compound could be included as an active ingredient in products intended to address pigmentation disorders.8
Anti-inflammatory activity
Inflammation is well known to trigger the production of melanin. This is why anti-inflammatory ingredients are often included in skin lighting products. A. capillaris displays anti-inflammatory activity and has shown some antioxidant activity.
In 2018, Lee et al. confirmed the therapeutic potential of A. capillaris extract to treat psoriasis in HaCaT cells and imiquimod-induced psoriasis-like mouse models. In the murine models, those treated with the ethanol extract of A. capillaris had a significantly lower Psoriasis Area and Severity Index score than that of the mice not given the topical application of the botanical. Epidermal thickness was noted to be significantly lower compared with the mice not treated with A. capillaris.9 Further studies in mice by the same team later that year supported the use of a cream formulation containing A. capillaris that they developed to treat psoriasis, warranting new investigations in human skin.10
Yeo et al. reported, earlier in 2018, on other anti-inflammatory activity of the herb, finding that the aqueous extract from A. capillaris blocked acute gastric mucosal injury by hindering reactive oxygen species and nuclear factor kappa B. They added that A. capillaris maintains oxidant/antioxidant homeostasis and displays potential as a nutraceutical agent for treating gastric ulcers and gastritis.5
In 2011, Kwon et al. studied the 5-lipoxygenase inhibitory action of a 70% ethanol extract of aerial parts of A. capillaris. They identified esculetin and quercetin as strong inhibitors of 5-lipoxygenase. The botanical agent, and esculetin in particular, robustly suppressed arachidonic acid-induced ear edema in mice as well as delayed-type hypersensitivity reactions. Further, A. capillaris potently blocked 5-lipoxygenase-catalyzed leukotriene synthesis by ionophore-induced rat basophilic leukemia-1 cells. The researchers concluded that their findings may partially account for the use of A. capillaris as a traditional medical treatment for cutaneous inflammatory conditions.2
Atopic dermatitis and A. capillaris
In 2014, Ha et al. used in vitro and in vivo systems to assess the anti-inflammatory effects of A. capillaris as well as its activity against atopic dermatitis. The in vitro studies revealed that A. capillaris hampered NO and cellular histamine synthesis. In Nc/Nga mice sensitized by Dermatophagoides farinae, dermatitis scores as well as hemorrhage, hypertrophy, and hyperkeratosis of the epidermis in the dorsal skin and ear all declined after the topical application of A. capillaris. Plasma levels of histamine and IgE also significantly decreased after treatment with A. capillaris. The investigators concluded that further study of A. capillaris is warranted as a potential therapeutic option for atopic dermatitis.11
Summary
Many botanical ingredients from Asia are making their way into skin care products in the USA. A. capillaris extract is an example and may have utility in treating hyperpigmentation-associated skin issues such as melasma. Its inhibitory effects on both inflammation and melanin production in addition to possible antioxidant activity make it an interesting compound worthy of more scrutiny.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.
References
1. Bora KS and Sharma A. Pharm Biol. 2011 Jan;49(1):101-9.
2. Kwon OS et al. Arch Pharm Res. 2011 Sep;34(9):1561-9.
3. Hsueh TP et al. Biomedicines. 2021 Oct 8;9(10):1412.
4. Dolinska MB et al. Int J Mol Sci. 2020 Jan 3;21(1):331.
5. Yeo D et al. Biomed Pharmacother. 2018 Mar;99:681-7.
6. Kim YS et al. J Food Sci. 2008 Jan;73(1):T16-20.
7. Kim MJ et al. Mol Med Rep. 2022 Apr;25(4):113.
8. Tabassum N et al. Evid Based Complement Alternat Med. 2016;2016:7823541.
9. Lee SY et al. Phytother Res. 2018 May;32(5):923-2.
10. Lee SY et al. Evid Based Complement Alternat Med. 2018 Aug 19;2018:3610494.
11. Ha H et al. BMC Complement Altern Med. 2014 Mar 14;14:100.
Melasma is a difficult disorder to treat. With the removal of hydroquinone from the cosmetic market and the prevalence of dyschromia, new skin lightening ingredients are being sought and many new discoveries are coming from Asia.
There are more than 500 species of the genus Artemisia (of the Astraceae or Compositae family) dispersed throughout the temperate areas of Asia, Europe, and North America.1 Various parts of the shrub Artemisia capillaris, found abundantly in China, Japan, and Korea, have been used in traditional medicine in Asia for hundreds of years. A. capillaris (Yin-Chen in Chinese) has been deployed in traditional Chinese medicine as a diuretic, to protect the liver, and to treat skin inflammation.2,3 Antioxidant, anti-inflammatory, antisteatotic, antitumor, and antiviral properties have been associated with this plant,3 and hydrating effects have been recently attributed to it. In Korean medicine, A. capillaris (InJin in Korean) has been used for its hepatoprotective, analgesic, and antipyretic activities.4,5 In this column, the focus will be on recent evidence that suggests possible applications in skin care.
Chemical constituents
In 2008, Kim et al. studied the anticarcinogenic activity of A. capillaris, among other medicinal herbs, using the 7,12-dimethylbenz[a]anthracene (DMBA)-induced mouse skin carcinogenesis model. The researchers found that A. capillaris exhibited the most effective anticarcinogenic activity compared to the other herbs tested, with such properties ascribed to its constituent camphor, 1-borneol, coumarin, and achillin. Notably, the chloroform fraction of A. capillaris significantly lowered the number of tumors/mouse and tumor incidence compared with the other tested herbs.6
The wide range of biological functions associated with A. capillaris, including anti-inflammatory, antioxidant, antidiabetic, antisteatotic, and antitumor activities have, in various studies, been attributed to the bioactive constituents scoparone, scopoletin, capillarisin, capillin, and chlorogenic acids.3
Tyrosinase-related protein 1 (TYRP-1) and its role in skin pigmentation
Tyrosinase related protein 1 (TYRP-1) is structurally similar to tyrosinase, but its role is still being elucidated. Mutations in TYR-1 results in oculocutaneous albinism. TYRP-1 is involved in eumelanin synthesis, but not in pheomelanin synthesis. Mutations in TYRP-1 affect the quality of melanin synthesized rather than the quantity.4 TYRP-1 is being looked at as a target for treatment of hyperpigmentation disorders such as melasma.
Effects on melanin synthesis
A. capillaris reduces the expression of TYRP-1, making it attractive for use in skin lightening products. Although there are not a lot of data, this is a developing area of interest and the following will discuss what is known so far.
Kim et al. investigated the antimelanogenic activity of 10 essential oils, including A. capillaris, utilizing the B16F10 cell line model. A. capillaris was among four extracts found to hinder melanogenesis, and the only one that improved cell proliferation, displayed anti-H2O2 activity, and reduced tyrosinase-related protein (TRP)-1 expression. The researchers determined that A. capillaris extract suppressed melanin production through the downregulation of the TRP 1 translational level. They concluded that while investigations using in vivo models are necessary to buttress and validate these results, A. capillaris extract appears to be suitable as a natural therapeutic antimelanogenic agent as well as a skin-whitening ingredient in cosmeceutical products.7
Tabassum et al. screened A. capillaris for antipigmentary functions using murine cultured cells (B16-F10 malignant melanocytes). They found that the A. capillaris constituent 4,5-O-dicaffeoylquinic acid significantly and dose-dependently diminished melanin production and tyrosinase activity in the melanocytes. The expression of tyrosinase-related protein-1 was also decreased. Further, the researchers observed antipigmentary activity in a zebrafish model, with no toxicity demonstrated by either A. capillaris or its component 4,5-O-dicaffeoylquinic acid. They concluded that this compound could be included as an active ingredient in products intended to address pigmentation disorders.8
Anti-inflammatory activity
Inflammation is well known to trigger the production of melanin. This is why anti-inflammatory ingredients are often included in skin lighting products. A. capillaris displays anti-inflammatory activity and has shown some antioxidant activity.
In 2018, Lee et al. confirmed the therapeutic potential of A. capillaris extract to treat psoriasis in HaCaT cells and imiquimod-induced psoriasis-like mouse models. In the murine models, those treated with the ethanol extract of A. capillaris had a significantly lower Psoriasis Area and Severity Index score than that of the mice not given the topical application of the botanical. Epidermal thickness was noted to be significantly lower compared with the mice not treated with A. capillaris.9 Further studies in mice by the same team later that year supported the use of a cream formulation containing A. capillaris that they developed to treat psoriasis, warranting new investigations in human skin.10
Yeo et al. reported, earlier in 2018, on other anti-inflammatory activity of the herb, finding that the aqueous extract from A. capillaris blocked acute gastric mucosal injury by hindering reactive oxygen species and nuclear factor kappa B. They added that A. capillaris maintains oxidant/antioxidant homeostasis and displays potential as a nutraceutical agent for treating gastric ulcers and gastritis.5
In 2011, Kwon et al. studied the 5-lipoxygenase inhibitory action of a 70% ethanol extract of aerial parts of A. capillaris. They identified esculetin and quercetin as strong inhibitors of 5-lipoxygenase. The botanical agent, and esculetin in particular, robustly suppressed arachidonic acid-induced ear edema in mice as well as delayed-type hypersensitivity reactions. Further, A. capillaris potently blocked 5-lipoxygenase-catalyzed leukotriene synthesis by ionophore-induced rat basophilic leukemia-1 cells. The researchers concluded that their findings may partially account for the use of A. capillaris as a traditional medical treatment for cutaneous inflammatory conditions.2
Atopic dermatitis and A. capillaris
In 2014, Ha et al. used in vitro and in vivo systems to assess the anti-inflammatory effects of A. capillaris as well as its activity against atopic dermatitis. The in vitro studies revealed that A. capillaris hampered NO and cellular histamine synthesis. In Nc/Nga mice sensitized by Dermatophagoides farinae, dermatitis scores as well as hemorrhage, hypertrophy, and hyperkeratosis of the epidermis in the dorsal skin and ear all declined after the topical application of A. capillaris. Plasma levels of histamine and IgE also significantly decreased after treatment with A. capillaris. The investigators concluded that further study of A. capillaris is warranted as a potential therapeutic option for atopic dermatitis.11
Summary
Many botanical ingredients from Asia are making their way into skin care products in the USA. A. capillaris extract is an example and may have utility in treating hyperpigmentation-associated skin issues such as melasma. Its inhibitory effects on both inflammation and melanin production in addition to possible antioxidant activity make it an interesting compound worthy of more scrutiny.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.
References
1. Bora KS and Sharma A. Pharm Biol. 2011 Jan;49(1):101-9.
2. Kwon OS et al. Arch Pharm Res. 2011 Sep;34(9):1561-9.
3. Hsueh TP et al. Biomedicines. 2021 Oct 8;9(10):1412.
4. Dolinska MB et al. Int J Mol Sci. 2020 Jan 3;21(1):331.
5. Yeo D et al. Biomed Pharmacother. 2018 Mar;99:681-7.
6. Kim YS et al. J Food Sci. 2008 Jan;73(1):T16-20.
7. Kim MJ et al. Mol Med Rep. 2022 Apr;25(4):113.
8. Tabassum N et al. Evid Based Complement Alternat Med. 2016;2016:7823541.
9. Lee SY et al. Phytother Res. 2018 May;32(5):923-2.
10. Lee SY et al. Evid Based Complement Alternat Med. 2018 Aug 19;2018:3610494.
11. Ha H et al. BMC Complement Altern Med. 2014 Mar 14;14:100.
Melasma is a difficult disorder to treat. With the removal of hydroquinone from the cosmetic market and the prevalence of dyschromia, new skin lightening ingredients are being sought and many new discoveries are coming from Asia.
There are more than 500 species of the genus Artemisia (of the Astraceae or Compositae family) dispersed throughout the temperate areas of Asia, Europe, and North America.1 Various parts of the shrub Artemisia capillaris, found abundantly in China, Japan, and Korea, have been used in traditional medicine in Asia for hundreds of years. A. capillaris (Yin-Chen in Chinese) has been deployed in traditional Chinese medicine as a diuretic, to protect the liver, and to treat skin inflammation.2,3 Antioxidant, anti-inflammatory, antisteatotic, antitumor, and antiviral properties have been associated with this plant,3 and hydrating effects have been recently attributed to it. In Korean medicine, A. capillaris (InJin in Korean) has been used for its hepatoprotective, analgesic, and antipyretic activities.4,5 In this column, the focus will be on recent evidence that suggests possible applications in skin care.
Chemical constituents
In 2008, Kim et al. studied the anticarcinogenic activity of A. capillaris, among other medicinal herbs, using the 7,12-dimethylbenz[a]anthracene (DMBA)-induced mouse skin carcinogenesis model. The researchers found that A. capillaris exhibited the most effective anticarcinogenic activity compared to the other herbs tested, with such properties ascribed to its constituent camphor, 1-borneol, coumarin, and achillin. Notably, the chloroform fraction of A. capillaris significantly lowered the number of tumors/mouse and tumor incidence compared with the other tested herbs.6
The wide range of biological functions associated with A. capillaris, including anti-inflammatory, antioxidant, antidiabetic, antisteatotic, and antitumor activities have, in various studies, been attributed to the bioactive constituents scoparone, scopoletin, capillarisin, capillin, and chlorogenic acids.3
Tyrosinase-related protein 1 (TYRP-1) and its role in skin pigmentation
Tyrosinase related protein 1 (TYRP-1) is structurally similar to tyrosinase, but its role is still being elucidated. Mutations in TYR-1 results in oculocutaneous albinism. TYRP-1 is involved in eumelanin synthesis, but not in pheomelanin synthesis. Mutations in TYRP-1 affect the quality of melanin synthesized rather than the quantity.4 TYRP-1 is being looked at as a target for treatment of hyperpigmentation disorders such as melasma.
Effects on melanin synthesis
A. capillaris reduces the expression of TYRP-1, making it attractive for use in skin lightening products. Although there are not a lot of data, this is a developing area of interest and the following will discuss what is known so far.
Kim et al. investigated the antimelanogenic activity of 10 essential oils, including A. capillaris, utilizing the B16F10 cell line model. A. capillaris was among four extracts found to hinder melanogenesis, and the only one that improved cell proliferation, displayed anti-H2O2 activity, and reduced tyrosinase-related protein (TRP)-1 expression. The researchers determined that A. capillaris extract suppressed melanin production through the downregulation of the TRP 1 translational level. They concluded that while investigations using in vivo models are necessary to buttress and validate these results, A. capillaris extract appears to be suitable as a natural therapeutic antimelanogenic agent as well as a skin-whitening ingredient in cosmeceutical products.7
Tabassum et al. screened A. capillaris for antipigmentary functions using murine cultured cells (B16-F10 malignant melanocytes). They found that the A. capillaris constituent 4,5-O-dicaffeoylquinic acid significantly and dose-dependently diminished melanin production and tyrosinase activity in the melanocytes. The expression of tyrosinase-related protein-1 was also decreased. Further, the researchers observed antipigmentary activity in a zebrafish model, with no toxicity demonstrated by either A. capillaris or its component 4,5-O-dicaffeoylquinic acid. They concluded that this compound could be included as an active ingredient in products intended to address pigmentation disorders.8
Anti-inflammatory activity
Inflammation is well known to trigger the production of melanin. This is why anti-inflammatory ingredients are often included in skin lighting products. A. capillaris displays anti-inflammatory activity and has shown some antioxidant activity.
In 2018, Lee et al. confirmed the therapeutic potential of A. capillaris extract to treat psoriasis in HaCaT cells and imiquimod-induced psoriasis-like mouse models. In the murine models, those treated with the ethanol extract of A. capillaris had a significantly lower Psoriasis Area and Severity Index score than that of the mice not given the topical application of the botanical. Epidermal thickness was noted to be significantly lower compared with the mice not treated with A. capillaris.9 Further studies in mice by the same team later that year supported the use of a cream formulation containing A. capillaris that they developed to treat psoriasis, warranting new investigations in human skin.10
Yeo et al. reported, earlier in 2018, on other anti-inflammatory activity of the herb, finding that the aqueous extract from A. capillaris blocked acute gastric mucosal injury by hindering reactive oxygen species and nuclear factor kappa B. They added that A. capillaris maintains oxidant/antioxidant homeostasis and displays potential as a nutraceutical agent for treating gastric ulcers and gastritis.5
In 2011, Kwon et al. studied the 5-lipoxygenase inhibitory action of a 70% ethanol extract of aerial parts of A. capillaris. They identified esculetin and quercetin as strong inhibitors of 5-lipoxygenase. The botanical agent, and esculetin in particular, robustly suppressed arachidonic acid-induced ear edema in mice as well as delayed-type hypersensitivity reactions. Further, A. capillaris potently blocked 5-lipoxygenase-catalyzed leukotriene synthesis by ionophore-induced rat basophilic leukemia-1 cells. The researchers concluded that their findings may partially account for the use of A. capillaris as a traditional medical treatment for cutaneous inflammatory conditions.2
Atopic dermatitis and A. capillaris
In 2014, Ha et al. used in vitro and in vivo systems to assess the anti-inflammatory effects of A. capillaris as well as its activity against atopic dermatitis. The in vitro studies revealed that A. capillaris hampered NO and cellular histamine synthesis. In Nc/Nga mice sensitized by Dermatophagoides farinae, dermatitis scores as well as hemorrhage, hypertrophy, and hyperkeratosis of the epidermis in the dorsal skin and ear all declined after the topical application of A. capillaris. Plasma levels of histamine and IgE also significantly decreased after treatment with A. capillaris. The investigators concluded that further study of A. capillaris is warranted as a potential therapeutic option for atopic dermatitis.11
Summary
Many botanical ingredients from Asia are making their way into skin care products in the USA. A. capillaris extract is an example and may have utility in treating hyperpigmentation-associated skin issues such as melasma. Its inhibitory effects on both inflammation and melanin production in addition to possible antioxidant activity make it an interesting compound worthy of more scrutiny.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.
References
1. Bora KS and Sharma A. Pharm Biol. 2011 Jan;49(1):101-9.
2. Kwon OS et al. Arch Pharm Res. 2011 Sep;34(9):1561-9.
3. Hsueh TP et al. Biomedicines. 2021 Oct 8;9(10):1412.
4. Dolinska MB et al. Int J Mol Sci. 2020 Jan 3;21(1):331.
5. Yeo D et al. Biomed Pharmacother. 2018 Mar;99:681-7.
6. Kim YS et al. J Food Sci. 2008 Jan;73(1):T16-20.
7. Kim MJ et al. Mol Med Rep. 2022 Apr;25(4):113.
8. Tabassum N et al. Evid Based Complement Alternat Med. 2016;2016:7823541.
9. Lee SY et al. Phytother Res. 2018 May;32(5):923-2.
10. Lee SY et al. Evid Based Complement Alternat Med. 2018 Aug 19;2018:3610494.
11. Ha H et al. BMC Complement Altern Med. 2014 Mar 14;14:100.
Is benzophenone safe in skin care? Part 2: Environmental effects
Although it has been . DiNardo and Downs point out that BP-3 has been linked to contact and photocontact allergies in humans and implicated as a potential endocrine disruptor. They add that it can yield deleterious by-products when reacting with chlorine in swimming pools and wastewater treatment plants and can cause additional side effects in humans who ingest fish.1 This column will focus on recent studies, mainly on the role of benzophenones in sunscreen agents that pose considerable risks to waterways and marine life, with concomitant effects on the food chain.
Environmental effects of BPs and legislative responses
Various UV filters, including BP-3, octinoxate, octocrylene, and ethylhexyl salicylate, are thought to pose considerable peril to the marine environment.2,3 In particular, BP-3 has been demonstrated to provoke coral reef bleaching in vitro, leading to ossification and deforming DNA in the larval stage.3,4
According to a 2018 report, BP-3 is believed to be present in approximately two thirds of organic sunscreens used in the United States.3 In addition, several studies have revealed that detectable levels of organic sunscreen ingredients, including BP-3, have been identified in coastal waters around the globe, including Hawaii and the U.S. Virgin Islands.4-8
A surfeit of tourists has been blamed in part, given that an estimated 25% of applied sunscreen is eliminated within 20 minutes of entering the water and thought to release about 4,000-6,000 tons/year into the surrounding coral reefs.9,10 In Hawaii in particular, sewage contamination of the waterways has resulted from wastewater treatment facilities ill-equipped to filter out organic substances such as BP-3 and octinoxate.10,11 In light of such circumstances, the use of sunscreens containing BP-3 and octinoxate have been restricted in Hawaii, particularly in proximity to beaches, since Jan. 1, 2021, because of their apparent environmental impact.10
The exposure of coral to these compounds is believed to result in bleaching because of impaired membrane integrity and photosynthetic pigment loss in the zooxanthellae that coral releases.9,10 Coral and the algae zooxanthellae have a symbiotic relationship, Siller et al. explain, with the coral delivering protection and components essential for photosynthesis and the algae ultimately serving as nutrients for the coral.10 Stress endured by coral is believed to cause algae to detach, rendering coral more vulnerable to disease and less viable overall.10
In 2016, Downs et al. showed that four out of five sampled locations had detectable levels of BP-3 (100 pp trillion) with a fifth tested site measured at 19.2 pp billion.4
In 2019, Sirois acknowledges the problem of coral bleaching around the world but speculates that banning sunscreen ingredients for this purpose will delude people that such a measure will reverse the decline of coral and may lead to the unintended consequence of lower use of sunscreens. Sirois adds that a more comprehensive investigation of the multiple causes of coral reef bleaching is warranted, as are deeper examinations of studies using higher concentrations of sunscreen ingredients in artificial conditions.12
In the same year, Raffa et al. discussed the impending ban in Hawaii of the two sunscreen ingredients (BP-3 and octinoxate) to help preserve coral reefs. In so doing, they detailed the natural and human-induced harm to coral reefs, including pollution, fishing practices, overall impact of global climate change, and alterations in ocean temperature and chemistry. The implication is that sunscreen ingredients, which help prevent sun damage in users, are not the only causes of harm to coral reefs. Nevertheless, they point out that concentration estimates and mechanism studies buttress the argument that sunscreen ingredients contribute to coral bleaching. Still, the ban in Hawaii is thought to be a trend. Opponents of the ban are concerned that human skin cancers will rise in such circumstances. Alternative chemical sunscreens are being investigated, and physical sunscreens have emerged as the go-to recommendation.13
Notably, oxybenzone has been virtually replaced in the European Union with other UV filters with broad-spectrum action, but the majority of such filters have not yet been approved for use in the United States by the Food and Drug Administration.3
Food chain implications
BP-3 and other UV filters have been investigated for their effects on fish and mammals. Schneider and Lim illustrate that BP-3 is among the frequently used organic UV filters (along with 4-methylbenzylidene camphor, octocrylene, and octinoxate [ethylhexyl methoxycinnamate]) found in most water sources in the world, as well as multiple fish species.2 Cod liver in Norway, for instance, was found to contain octocrylene in 80% of cod, with BP-3 identified in 50% of the sample. BP-3 and octinoxate were also found in white fish.2,14 In laboratory studies, BP-3 in particular has been found in high concentrations in rainbow trout and Japanese rice fish (medaka), causing reduced egg production and hatchlings in females and increased vitellogenin protein production in males, suggesting potential feminization.2,15
Schneider and Lim note that standard wastewater treatment approaches cannot address this issue and the presence of such contaminants in fish can pose dangerous ramifications in the food chain. They assert that, despite relatively low concentrations in the fish, bioaccumulation and biomagnification present the potential for chemicals accumulating over time and becoming more deleterious as such ingredients travel up the food chain. As higher-chain organisms absorb higher concentrations of the chemicals not broken down in the lower-chain organisms, though, there have not yet been reports of adverse effects of biomagnification in humans.2
BP-3 has been found by Brausch and Rand to have bioaccumulated in fish at higher levels than the ambient water, however.1,2,16 Schneider and Lim present these issues as relevant to the sun protection discussion, while advocating for dermatologists to continue to counsel wise sun-protective behaviors.2
Conclusion
While calls for additional research are necessary and encouraging, I think human, and likely environmental, health would be better protected by the use of inorganic sunscreens in general and near or in coastal waterways. In light of legislative actions, in particular, it is important for dermatologists to intervene to ensure that patients do not engage in riskier behaviors in the sun in areas facing imminent organic sunscreen bans.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.
References
1. DiNardo JC and Downs CA. J Cosmet Dermatol. 2018 Feb;17(1):15-9.
2. Schneider SL and Lim HW. J Am Acad Dermatol. 2019 Jan;80(1):266-71.
3. Yeager DG and Lim HW. Dermatol Clin. 2019 Apr;37(2):149-57.
4. Downs CA et al. Arch Environ Contam Toxicol 2016 Feb;70(2):265-88.
5. Sánchez Rodríguez A et al. Chemosphere. 2015 Jul;131:85-90.
6. Tovar-Sánchez A et al. PLoS One. 2013 Jun 5;8(6):e65451.
7. Danovaro R and Corinaldesi C. Microb Ecol. 2003 Feb;45(2):109-18.
8. Daughton CG and Ternes TA. Environ Health Perspect. 1999 Dec;107 Suppl 6:907-38.
9. Danovaro R et al. Environ Health Perspect. 2008 Apr;116(4):441-7.
10. Siller A et al. Plast Surg Nur. 2019 Oct/Dec;39(4):157-60.
11. Ramos S et al. Sci Total Environ. 2015 Sep 1;526:278-311.
12. Sirois J. Sci Total Environ. 2019 Jul 15;674:211-2.
13. Raffa RB et al. J Clin Pharm Ther. 2019 Feb;44(1):134-9.
14. Langford KH et al. Environ Int. 2015 Jul;80:1-7.
15. Coronado M et al. Aquat Toxicol. 2008 Nov 21;90(3):182-7.
16. Brausch JM and Rand GM. Chemosphere. 2011 Mar;82(11):1518-32.
Although it has been . DiNardo and Downs point out that BP-3 has been linked to contact and photocontact allergies in humans and implicated as a potential endocrine disruptor. They add that it can yield deleterious by-products when reacting with chlorine in swimming pools and wastewater treatment plants and can cause additional side effects in humans who ingest fish.1 This column will focus on recent studies, mainly on the role of benzophenones in sunscreen agents that pose considerable risks to waterways and marine life, with concomitant effects on the food chain.
Environmental effects of BPs and legislative responses
Various UV filters, including BP-3, octinoxate, octocrylene, and ethylhexyl salicylate, are thought to pose considerable peril to the marine environment.2,3 In particular, BP-3 has been demonstrated to provoke coral reef bleaching in vitro, leading to ossification and deforming DNA in the larval stage.3,4
According to a 2018 report, BP-3 is believed to be present in approximately two thirds of organic sunscreens used in the United States.3 In addition, several studies have revealed that detectable levels of organic sunscreen ingredients, including BP-3, have been identified in coastal waters around the globe, including Hawaii and the U.S. Virgin Islands.4-8
A surfeit of tourists has been blamed in part, given that an estimated 25% of applied sunscreen is eliminated within 20 minutes of entering the water and thought to release about 4,000-6,000 tons/year into the surrounding coral reefs.9,10 In Hawaii in particular, sewage contamination of the waterways has resulted from wastewater treatment facilities ill-equipped to filter out organic substances such as BP-3 and octinoxate.10,11 In light of such circumstances, the use of sunscreens containing BP-3 and octinoxate have been restricted in Hawaii, particularly in proximity to beaches, since Jan. 1, 2021, because of their apparent environmental impact.10
The exposure of coral to these compounds is believed to result in bleaching because of impaired membrane integrity and photosynthetic pigment loss in the zooxanthellae that coral releases.9,10 Coral and the algae zooxanthellae have a symbiotic relationship, Siller et al. explain, with the coral delivering protection and components essential for photosynthesis and the algae ultimately serving as nutrients for the coral.10 Stress endured by coral is believed to cause algae to detach, rendering coral more vulnerable to disease and less viable overall.10
In 2016, Downs et al. showed that four out of five sampled locations had detectable levels of BP-3 (100 pp trillion) with a fifth tested site measured at 19.2 pp billion.4
In 2019, Sirois acknowledges the problem of coral bleaching around the world but speculates that banning sunscreen ingredients for this purpose will delude people that such a measure will reverse the decline of coral and may lead to the unintended consequence of lower use of sunscreens. Sirois adds that a more comprehensive investigation of the multiple causes of coral reef bleaching is warranted, as are deeper examinations of studies using higher concentrations of sunscreen ingredients in artificial conditions.12
In the same year, Raffa et al. discussed the impending ban in Hawaii of the two sunscreen ingredients (BP-3 and octinoxate) to help preserve coral reefs. In so doing, they detailed the natural and human-induced harm to coral reefs, including pollution, fishing practices, overall impact of global climate change, and alterations in ocean temperature and chemistry. The implication is that sunscreen ingredients, which help prevent sun damage in users, are not the only causes of harm to coral reefs. Nevertheless, they point out that concentration estimates and mechanism studies buttress the argument that sunscreen ingredients contribute to coral bleaching. Still, the ban in Hawaii is thought to be a trend. Opponents of the ban are concerned that human skin cancers will rise in such circumstances. Alternative chemical sunscreens are being investigated, and physical sunscreens have emerged as the go-to recommendation.13
Notably, oxybenzone has been virtually replaced in the European Union with other UV filters with broad-spectrum action, but the majority of such filters have not yet been approved for use in the United States by the Food and Drug Administration.3
Food chain implications
BP-3 and other UV filters have been investigated for their effects on fish and mammals. Schneider and Lim illustrate that BP-3 is among the frequently used organic UV filters (along with 4-methylbenzylidene camphor, octocrylene, and octinoxate [ethylhexyl methoxycinnamate]) found in most water sources in the world, as well as multiple fish species.2 Cod liver in Norway, for instance, was found to contain octocrylene in 80% of cod, with BP-3 identified in 50% of the sample. BP-3 and octinoxate were also found in white fish.2,14 In laboratory studies, BP-3 in particular has been found in high concentrations in rainbow trout and Japanese rice fish (medaka), causing reduced egg production and hatchlings in females and increased vitellogenin protein production in males, suggesting potential feminization.2,15
Schneider and Lim note that standard wastewater treatment approaches cannot address this issue and the presence of such contaminants in fish can pose dangerous ramifications in the food chain. They assert that, despite relatively low concentrations in the fish, bioaccumulation and biomagnification present the potential for chemicals accumulating over time and becoming more deleterious as such ingredients travel up the food chain. As higher-chain organisms absorb higher concentrations of the chemicals not broken down in the lower-chain organisms, though, there have not yet been reports of adverse effects of biomagnification in humans.2
BP-3 has been found by Brausch and Rand to have bioaccumulated in fish at higher levels than the ambient water, however.1,2,16 Schneider and Lim present these issues as relevant to the sun protection discussion, while advocating for dermatologists to continue to counsel wise sun-protective behaviors.2
Conclusion
While calls for additional research are necessary and encouraging, I think human, and likely environmental, health would be better protected by the use of inorganic sunscreens in general and near or in coastal waterways. In light of legislative actions, in particular, it is important for dermatologists to intervene to ensure that patients do not engage in riskier behaviors in the sun in areas facing imminent organic sunscreen bans.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.
References
1. DiNardo JC and Downs CA. J Cosmet Dermatol. 2018 Feb;17(1):15-9.
2. Schneider SL and Lim HW. J Am Acad Dermatol. 2019 Jan;80(1):266-71.
3. Yeager DG and Lim HW. Dermatol Clin. 2019 Apr;37(2):149-57.
4. Downs CA et al. Arch Environ Contam Toxicol 2016 Feb;70(2):265-88.
5. Sánchez Rodríguez A et al. Chemosphere. 2015 Jul;131:85-90.
6. Tovar-Sánchez A et al. PLoS One. 2013 Jun 5;8(6):e65451.
7. Danovaro R and Corinaldesi C. Microb Ecol. 2003 Feb;45(2):109-18.
8. Daughton CG and Ternes TA. Environ Health Perspect. 1999 Dec;107 Suppl 6:907-38.
9. Danovaro R et al. Environ Health Perspect. 2008 Apr;116(4):441-7.
10. Siller A et al. Plast Surg Nur. 2019 Oct/Dec;39(4):157-60.
11. Ramos S et al. Sci Total Environ. 2015 Sep 1;526:278-311.
12. Sirois J. Sci Total Environ. 2019 Jul 15;674:211-2.
13. Raffa RB et al. J Clin Pharm Ther. 2019 Feb;44(1):134-9.
14. Langford KH et al. Environ Int. 2015 Jul;80:1-7.
15. Coronado M et al. Aquat Toxicol. 2008 Nov 21;90(3):182-7.
16. Brausch JM and Rand GM. Chemosphere. 2011 Mar;82(11):1518-32.
Although it has been . DiNardo and Downs point out that BP-3 has been linked to contact and photocontact allergies in humans and implicated as a potential endocrine disruptor. They add that it can yield deleterious by-products when reacting with chlorine in swimming pools and wastewater treatment plants and can cause additional side effects in humans who ingest fish.1 This column will focus on recent studies, mainly on the role of benzophenones in sunscreen agents that pose considerable risks to waterways and marine life, with concomitant effects on the food chain.
Environmental effects of BPs and legislative responses
Various UV filters, including BP-3, octinoxate, octocrylene, and ethylhexyl salicylate, are thought to pose considerable peril to the marine environment.2,3 In particular, BP-3 has been demonstrated to provoke coral reef bleaching in vitro, leading to ossification and deforming DNA in the larval stage.3,4
According to a 2018 report, BP-3 is believed to be present in approximately two thirds of organic sunscreens used in the United States.3 In addition, several studies have revealed that detectable levels of organic sunscreen ingredients, including BP-3, have been identified in coastal waters around the globe, including Hawaii and the U.S. Virgin Islands.4-8
A surfeit of tourists has been blamed in part, given that an estimated 25% of applied sunscreen is eliminated within 20 minutes of entering the water and thought to release about 4,000-6,000 tons/year into the surrounding coral reefs.9,10 In Hawaii in particular, sewage contamination of the waterways has resulted from wastewater treatment facilities ill-equipped to filter out organic substances such as BP-3 and octinoxate.10,11 In light of such circumstances, the use of sunscreens containing BP-3 and octinoxate have been restricted in Hawaii, particularly in proximity to beaches, since Jan. 1, 2021, because of their apparent environmental impact.10
The exposure of coral to these compounds is believed to result in bleaching because of impaired membrane integrity and photosynthetic pigment loss in the zooxanthellae that coral releases.9,10 Coral and the algae zooxanthellae have a symbiotic relationship, Siller et al. explain, with the coral delivering protection and components essential for photosynthesis and the algae ultimately serving as nutrients for the coral.10 Stress endured by coral is believed to cause algae to detach, rendering coral more vulnerable to disease and less viable overall.10
In 2016, Downs et al. showed that four out of five sampled locations had detectable levels of BP-3 (100 pp trillion) with a fifth tested site measured at 19.2 pp billion.4
In 2019, Sirois acknowledges the problem of coral bleaching around the world but speculates that banning sunscreen ingredients for this purpose will delude people that such a measure will reverse the decline of coral and may lead to the unintended consequence of lower use of sunscreens. Sirois adds that a more comprehensive investigation of the multiple causes of coral reef bleaching is warranted, as are deeper examinations of studies using higher concentrations of sunscreen ingredients in artificial conditions.12
In the same year, Raffa et al. discussed the impending ban in Hawaii of the two sunscreen ingredients (BP-3 and octinoxate) to help preserve coral reefs. In so doing, they detailed the natural and human-induced harm to coral reefs, including pollution, fishing practices, overall impact of global climate change, and alterations in ocean temperature and chemistry. The implication is that sunscreen ingredients, which help prevent sun damage in users, are not the only causes of harm to coral reefs. Nevertheless, they point out that concentration estimates and mechanism studies buttress the argument that sunscreen ingredients contribute to coral bleaching. Still, the ban in Hawaii is thought to be a trend. Opponents of the ban are concerned that human skin cancers will rise in such circumstances. Alternative chemical sunscreens are being investigated, and physical sunscreens have emerged as the go-to recommendation.13
Notably, oxybenzone has been virtually replaced in the European Union with other UV filters with broad-spectrum action, but the majority of such filters have not yet been approved for use in the United States by the Food and Drug Administration.3
Food chain implications
BP-3 and other UV filters have been investigated for their effects on fish and mammals. Schneider and Lim illustrate that BP-3 is among the frequently used organic UV filters (along with 4-methylbenzylidene camphor, octocrylene, and octinoxate [ethylhexyl methoxycinnamate]) found in most water sources in the world, as well as multiple fish species.2 Cod liver in Norway, for instance, was found to contain octocrylene in 80% of cod, with BP-3 identified in 50% of the sample. BP-3 and octinoxate were also found in white fish.2,14 In laboratory studies, BP-3 in particular has been found in high concentrations in rainbow trout and Japanese rice fish (medaka), causing reduced egg production and hatchlings in females and increased vitellogenin protein production in males, suggesting potential feminization.2,15
Schneider and Lim note that standard wastewater treatment approaches cannot address this issue and the presence of such contaminants in fish can pose dangerous ramifications in the food chain. They assert that, despite relatively low concentrations in the fish, bioaccumulation and biomagnification present the potential for chemicals accumulating over time and becoming more deleterious as such ingredients travel up the food chain. As higher-chain organisms absorb higher concentrations of the chemicals not broken down in the lower-chain organisms, though, there have not yet been reports of adverse effects of biomagnification in humans.2
BP-3 has been found by Brausch and Rand to have bioaccumulated in fish at higher levels than the ambient water, however.1,2,16 Schneider and Lim present these issues as relevant to the sun protection discussion, while advocating for dermatologists to continue to counsel wise sun-protective behaviors.2
Conclusion
While calls for additional research are necessary and encouraging, I think human, and likely environmental, health would be better protected by the use of inorganic sunscreens in general and near or in coastal waterways. In light of legislative actions, in particular, it is important for dermatologists to intervene to ensure that patients do not engage in riskier behaviors in the sun in areas facing imminent organic sunscreen bans.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.
References
1. DiNardo JC and Downs CA. J Cosmet Dermatol. 2018 Feb;17(1):15-9.
2. Schneider SL and Lim HW. J Am Acad Dermatol. 2019 Jan;80(1):266-71.
3. Yeager DG and Lim HW. Dermatol Clin. 2019 Apr;37(2):149-57.
4. Downs CA et al. Arch Environ Contam Toxicol 2016 Feb;70(2):265-88.
5. Sánchez Rodríguez A et al. Chemosphere. 2015 Jul;131:85-90.
6. Tovar-Sánchez A et al. PLoS One. 2013 Jun 5;8(6):e65451.
7. Danovaro R and Corinaldesi C. Microb Ecol. 2003 Feb;45(2):109-18.
8. Daughton CG and Ternes TA. Environ Health Perspect. 1999 Dec;107 Suppl 6:907-38.
9. Danovaro R et al. Environ Health Perspect. 2008 Apr;116(4):441-7.
10. Siller A et al. Plast Surg Nur. 2019 Oct/Dec;39(4):157-60.
11. Ramos S et al. Sci Total Environ. 2015 Sep 1;526:278-311.
12. Sirois J. Sci Total Environ. 2019 Jul 15;674:211-2.
13. Raffa RB et al. J Clin Pharm Ther. 2019 Feb;44(1):134-9.
14. Langford KH et al. Environ Int. 2015 Jul;80:1-7.
15. Coronado M et al. Aquat Toxicol. 2008 Nov 21;90(3):182-7.
16. Brausch JM and Rand GM. Chemosphere. 2011 Mar;82(11):1518-32.
Is benzophenone safe in skin care? Part 1: Risks to humans
Benzophenones are a family of compounds that include dixoxybenzone, sulisobenzone, and benzophenone-3, or oxybenzone. These . Benzophenones (BPs) act as penetration enhancers, as they modify the structure of the skin and facilitate the absorption of other chemical ingredients into the body. The best known uses of these compounds are as perfume fixatives and sunscreen agents.
Sunscreens and benzophenones
BP-2, -3 and -4 are used as sunscreens but have many downsides. They are well known photoallergens, are toxic to aquatic animals (especially BP-3), and are found in urine. BP-2 has weak estrogenic effects, and some studies suggest that it decreases fertility in men. BP-4 can increase absorption of pesticides. BP-3 is banned in Hawaii because of the risk to coral and is the most worrisome.
In particular, BP-3 is known to protect skin and hair from UV radiation-induced harm.1 Unfortunately, BPs are also associated with photocontact allergies, hypersensitivity, hives, contact urticaria, anaphylaxis, hormone disruption, and DNA damage.2,3 BP-3 has also been implicated as an environmental contaminant. This column will focus on recent studies pertaining to effects on humans, primarily, and on the role of BPs in sunscreen agents.
Effects of BPs in animals
A recent study on the cytotoxicity of BP-3 against thymocytes in rats revealed that cell mortality increased significantly after 3 hours of exposure to 300 μM BP-3, but the membrane potential of thymocytes was unchanged by BP-3 exposure. In a concentration-dependent fashion, intracellular Zn2+ levels increased significantly after administration of at least 30 μM BP-3. The investigators concluded that the cytotoxicity engendered by BP-3 could be the result of oxidative stress linked to elevated intracellular Zn2+ levels.1
Effects of BPs in humans and systemic absorption
In multiple studies, exposure to BP-3, as well as to octinoxate, has been linked to endocrine and hormonal disruptions in humans and animals.4,5 Motivated by several notable observations (global increase in the use of sunscreens with UV filters; rapid rise in malignant melanoma, against which sunscreens should protect; increase in reported experimental findings of UV filters acting as endocrine disruptors), Krause et al. in 2012 reviewed animal and human data on the UV filters BP-3, 3-benzylidene camphor (3-BC), 3-(4-methyl-benzylidene) camphor (4-MBC), 2-ethylhexyl 4-methoxy cinnamate (OMC), homosalate (HMS), 2-ethylhexyl 4-dimethylaminobenzoate, and 4-aminobenzoic acid (PABA). Importantly, BP-3 was present in 96% of human urine samples in the United States, and various filters were found in 85% of the human breast milk samples in Switzerland.6
A 2019 analysis by Wang and Ganley reported that systemic absorption of the active sunscreen ingredient BP-3 can be substantial, justifying the assessment and understanding of systemic exposure to characterize the risks of long-term usage.7
Between January and February 2019, Matta et al. conducted a randomized clinical trial with 48 healthy participants to evaluate the systemic absorption and pharmacokinetics of six active ingredients in four sunscreen formulations, including avobenzone and BP-3. The researchers found that all ingredients were systemically absorbed, with plasma concentrations exceeding the Food and Drug Administration threshold for considering the waiving of further safety studies. They concluded that these results did not warrant discontinuing the use of the tested sunscreen ingredients.8 Yeager and Lim add that, while BP-3 has been incorporated into sunscreen formulations for sale in the United States since 1978, there have been no reports of adverse systemic reactions in human beings.3
However, topical reactions have elicited a different assessment. That is, in 2014, the American Contact Dermatitis Society labeled BPs the Contact Allergen of the Year, as they were identified as the most common source of photoallergic and contact allergic reactions of all UV filters.3,9
Risks of BPs in sunscreens and other skincare products
In 2015, Amar et al. investigated the photogenotoxicity and apoptotic effects in human keratinocytes (HaCaT cells) of BP-1, which is used as a UV blocker in sunscreens. They found that BP-1, when exposed to UV radiation, photosensitized cells and yielded intracellular reactive oxygen species. Significant reductions in cell viability were also seen with exposure to sunlight, UVA, and UVB. The researchers also confirmed genotoxic activity, with BP-1 augmenting lipid peroxidation and upregulating apoptotic proteins. They concluded that sunscreen users should be advised to avoid products that contain BP-1.10
In 2019, Amar et al. evaluated the effects of BPs on the differential expression of proteins in HaCaT cells exposed to UVA. Their findings indicated the expression of novel proteins that helped to initiate or promote apoptosis. They concluded that, because of the predilection to render such effects in human skin keratinocytes, consumers should avoid the use of sunscreens that contain BPs as UV blocking ingredients.11
Still widely used as an effective filter against UVA2 and UVB, BP-3 was believed to be present in two thirds of nonmineral sunscreens in the United States in 2018.3,12
Notably, BP-1 and BP-3 were found in small proportions (3.7% and 4.9%, respectively) among a total of 283 products culled from various stores in Lecce, Italy, in a survey of the potentially dangerous chemicals found in rinse-off, leave-on, and makeup products in 2019.13 The authors added that the International Agency for Research on Cancer, in 2010, classified BP as potentially carcinogenic to humans (2B group).13,14
Promising use of nanocapsules
The widespread concern about the phototoxicity of BP has prompted some interesting research into workarounds. Specifically, in 2019, Barbosa et al. reported on the creation of a new sunscreen formulation using polymeric nanocapsules loading BP-3. The nanocapsules are made of poly(ε-caprolactone) carrot oil and Pluronic F68 (nonionic surfactant used in suspension cultures), and the BP-3–loaded capsules were found to be noncytotoxic in L929 fibroblast cell lines with a sun protection factor of 8.64. The researchers concluded that this promising nanocapsule may be an effective and safe way to use lipophilic sunscreen ingredients such as BP-3.15
Conclusion
The body of evidence is weighted against the use of BPs. Luckily, we have safe sunscreen choices that allow us to protect our skin without using these compounds.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.
References
1. Utsunomiya H et al. Chem Biol Interact. 2019 Jan 25;298:52-6.
2. Schneider SL and Lim HW. J Am Acad Dermatol. 2019 Jan;80(1):266-71.
3. Yeager DG and Lim HW. Dermatol Clin. 2019 Apr;37(2):149-57.
4. Ramos S et al. Sci Total Environ. 2015 Sep 1;526:278-311.
5. Siller A et al. Plast Surg Nur. 2019 Oct/Dec;39(4):157-60.
6. Krause M et al. Int J Androl. 2012 Jun;35(3):424-36.
7. Wang J and Ganley CJ. Clin Pharmacol Ther. 2019 Jan;105(1):161-7.
8. Matta MK et al. JAMA. 2020 Jan 21;323(3):256-67.
9. Warshaw EM et al. Dermatitis. 2013 Jul-Aug;24(4):176-82.
10. Amar SK et al. Toxicol Lett. 2015 Dec 15;239(3):182-93.
11. Amar SK et al. Toxicol Ind Health. 2019 Jul;35(7):457-65.
12. EWG. The trouble with ingredients in sunscreens. Accessed on 4 April 2020.
13. Panico A et al. J Prev Med Hyg. 2019 Mar 29;60(1):E50-7.
14. International Agency for Research on Cancer (IARC). Benzophenone. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. WHO, IARC Press, Lyon, France. 2010;101:285-304.
15. Barbosa TC et al. Toxics. 2019 Sep 22;7(4):51.
Benzophenones are a family of compounds that include dixoxybenzone, sulisobenzone, and benzophenone-3, or oxybenzone. These . Benzophenones (BPs) act as penetration enhancers, as they modify the structure of the skin and facilitate the absorption of other chemical ingredients into the body. The best known uses of these compounds are as perfume fixatives and sunscreen agents.
Sunscreens and benzophenones
BP-2, -3 and -4 are used as sunscreens but have many downsides. They are well known photoallergens, are toxic to aquatic animals (especially BP-3), and are found in urine. BP-2 has weak estrogenic effects, and some studies suggest that it decreases fertility in men. BP-4 can increase absorption of pesticides. BP-3 is banned in Hawaii because of the risk to coral and is the most worrisome.
In particular, BP-3 is known to protect skin and hair from UV radiation-induced harm.1 Unfortunately, BPs are also associated with photocontact allergies, hypersensitivity, hives, contact urticaria, anaphylaxis, hormone disruption, and DNA damage.2,3 BP-3 has also been implicated as an environmental contaminant. This column will focus on recent studies pertaining to effects on humans, primarily, and on the role of BPs in sunscreen agents.
Effects of BPs in animals
A recent study on the cytotoxicity of BP-3 against thymocytes in rats revealed that cell mortality increased significantly after 3 hours of exposure to 300 μM BP-3, but the membrane potential of thymocytes was unchanged by BP-3 exposure. In a concentration-dependent fashion, intracellular Zn2+ levels increased significantly after administration of at least 30 μM BP-3. The investigators concluded that the cytotoxicity engendered by BP-3 could be the result of oxidative stress linked to elevated intracellular Zn2+ levels.1
Effects of BPs in humans and systemic absorption
In multiple studies, exposure to BP-3, as well as to octinoxate, has been linked to endocrine and hormonal disruptions in humans and animals.4,5 Motivated by several notable observations (global increase in the use of sunscreens with UV filters; rapid rise in malignant melanoma, against which sunscreens should protect; increase in reported experimental findings of UV filters acting as endocrine disruptors), Krause et al. in 2012 reviewed animal and human data on the UV filters BP-3, 3-benzylidene camphor (3-BC), 3-(4-methyl-benzylidene) camphor (4-MBC), 2-ethylhexyl 4-methoxy cinnamate (OMC), homosalate (HMS), 2-ethylhexyl 4-dimethylaminobenzoate, and 4-aminobenzoic acid (PABA). Importantly, BP-3 was present in 96% of human urine samples in the United States, and various filters were found in 85% of the human breast milk samples in Switzerland.6
A 2019 analysis by Wang and Ganley reported that systemic absorption of the active sunscreen ingredient BP-3 can be substantial, justifying the assessment and understanding of systemic exposure to characterize the risks of long-term usage.7
Between January and February 2019, Matta et al. conducted a randomized clinical trial with 48 healthy participants to evaluate the systemic absorption and pharmacokinetics of six active ingredients in four sunscreen formulations, including avobenzone and BP-3. The researchers found that all ingredients were systemically absorbed, with plasma concentrations exceeding the Food and Drug Administration threshold for considering the waiving of further safety studies. They concluded that these results did not warrant discontinuing the use of the tested sunscreen ingredients.8 Yeager and Lim add that, while BP-3 has been incorporated into sunscreen formulations for sale in the United States since 1978, there have been no reports of adverse systemic reactions in human beings.3
However, topical reactions have elicited a different assessment. That is, in 2014, the American Contact Dermatitis Society labeled BPs the Contact Allergen of the Year, as they were identified as the most common source of photoallergic and contact allergic reactions of all UV filters.3,9
Risks of BPs in sunscreens and other skincare products
In 2015, Amar et al. investigated the photogenotoxicity and apoptotic effects in human keratinocytes (HaCaT cells) of BP-1, which is used as a UV blocker in sunscreens. They found that BP-1, when exposed to UV radiation, photosensitized cells and yielded intracellular reactive oxygen species. Significant reductions in cell viability were also seen with exposure to sunlight, UVA, and UVB. The researchers also confirmed genotoxic activity, with BP-1 augmenting lipid peroxidation and upregulating apoptotic proteins. They concluded that sunscreen users should be advised to avoid products that contain BP-1.10
In 2019, Amar et al. evaluated the effects of BPs on the differential expression of proteins in HaCaT cells exposed to UVA. Their findings indicated the expression of novel proteins that helped to initiate or promote apoptosis. They concluded that, because of the predilection to render such effects in human skin keratinocytes, consumers should avoid the use of sunscreens that contain BPs as UV blocking ingredients.11
Still widely used as an effective filter against UVA2 and UVB, BP-3 was believed to be present in two thirds of nonmineral sunscreens in the United States in 2018.3,12
Notably, BP-1 and BP-3 were found in small proportions (3.7% and 4.9%, respectively) among a total of 283 products culled from various stores in Lecce, Italy, in a survey of the potentially dangerous chemicals found in rinse-off, leave-on, and makeup products in 2019.13 The authors added that the International Agency for Research on Cancer, in 2010, classified BP as potentially carcinogenic to humans (2B group).13,14
Promising use of nanocapsules
The widespread concern about the phototoxicity of BP has prompted some interesting research into workarounds. Specifically, in 2019, Barbosa et al. reported on the creation of a new sunscreen formulation using polymeric nanocapsules loading BP-3. The nanocapsules are made of poly(ε-caprolactone) carrot oil and Pluronic F68 (nonionic surfactant used in suspension cultures), and the BP-3–loaded capsules were found to be noncytotoxic in L929 fibroblast cell lines with a sun protection factor of 8.64. The researchers concluded that this promising nanocapsule may be an effective and safe way to use lipophilic sunscreen ingredients such as BP-3.15
Conclusion
The body of evidence is weighted against the use of BPs. Luckily, we have safe sunscreen choices that allow us to protect our skin without using these compounds.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.
References
1. Utsunomiya H et al. Chem Biol Interact. 2019 Jan 25;298:52-6.
2. Schneider SL and Lim HW. J Am Acad Dermatol. 2019 Jan;80(1):266-71.
3. Yeager DG and Lim HW. Dermatol Clin. 2019 Apr;37(2):149-57.
4. Ramos S et al. Sci Total Environ. 2015 Sep 1;526:278-311.
5. Siller A et al. Plast Surg Nur. 2019 Oct/Dec;39(4):157-60.
6. Krause M et al. Int J Androl. 2012 Jun;35(3):424-36.
7. Wang J and Ganley CJ. Clin Pharmacol Ther. 2019 Jan;105(1):161-7.
8. Matta MK et al. JAMA. 2020 Jan 21;323(3):256-67.
9. Warshaw EM et al. Dermatitis. 2013 Jul-Aug;24(4):176-82.
10. Amar SK et al. Toxicol Lett. 2015 Dec 15;239(3):182-93.
11. Amar SK et al. Toxicol Ind Health. 2019 Jul;35(7):457-65.
12. EWG. The trouble with ingredients in sunscreens. Accessed on 4 April 2020.
13. Panico A et al. J Prev Med Hyg. 2019 Mar 29;60(1):E50-7.
14. International Agency for Research on Cancer (IARC). Benzophenone. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. WHO, IARC Press, Lyon, France. 2010;101:285-304.
15. Barbosa TC et al. Toxics. 2019 Sep 22;7(4):51.
Benzophenones are a family of compounds that include dixoxybenzone, sulisobenzone, and benzophenone-3, or oxybenzone. These . Benzophenones (BPs) act as penetration enhancers, as they modify the structure of the skin and facilitate the absorption of other chemical ingredients into the body. The best known uses of these compounds are as perfume fixatives and sunscreen agents.
Sunscreens and benzophenones
BP-2, -3 and -4 are used as sunscreens but have many downsides. They are well known photoallergens, are toxic to aquatic animals (especially BP-3), and are found in urine. BP-2 has weak estrogenic effects, and some studies suggest that it decreases fertility in men. BP-4 can increase absorption of pesticides. BP-3 is banned in Hawaii because of the risk to coral and is the most worrisome.
In particular, BP-3 is known to protect skin and hair from UV radiation-induced harm.1 Unfortunately, BPs are also associated with photocontact allergies, hypersensitivity, hives, contact urticaria, anaphylaxis, hormone disruption, and DNA damage.2,3 BP-3 has also been implicated as an environmental contaminant. This column will focus on recent studies pertaining to effects on humans, primarily, and on the role of BPs in sunscreen agents.
Effects of BPs in animals
A recent study on the cytotoxicity of BP-3 against thymocytes in rats revealed that cell mortality increased significantly after 3 hours of exposure to 300 μM BP-3, but the membrane potential of thymocytes was unchanged by BP-3 exposure. In a concentration-dependent fashion, intracellular Zn2+ levels increased significantly after administration of at least 30 μM BP-3. The investigators concluded that the cytotoxicity engendered by BP-3 could be the result of oxidative stress linked to elevated intracellular Zn2+ levels.1
Effects of BPs in humans and systemic absorption
In multiple studies, exposure to BP-3, as well as to octinoxate, has been linked to endocrine and hormonal disruptions in humans and animals.4,5 Motivated by several notable observations (global increase in the use of sunscreens with UV filters; rapid rise in malignant melanoma, against which sunscreens should protect; increase in reported experimental findings of UV filters acting as endocrine disruptors), Krause et al. in 2012 reviewed animal and human data on the UV filters BP-3, 3-benzylidene camphor (3-BC), 3-(4-methyl-benzylidene) camphor (4-MBC), 2-ethylhexyl 4-methoxy cinnamate (OMC), homosalate (HMS), 2-ethylhexyl 4-dimethylaminobenzoate, and 4-aminobenzoic acid (PABA). Importantly, BP-3 was present in 96% of human urine samples in the United States, and various filters were found in 85% of the human breast milk samples in Switzerland.6
A 2019 analysis by Wang and Ganley reported that systemic absorption of the active sunscreen ingredient BP-3 can be substantial, justifying the assessment and understanding of systemic exposure to characterize the risks of long-term usage.7
Between January and February 2019, Matta et al. conducted a randomized clinical trial with 48 healthy participants to evaluate the systemic absorption and pharmacokinetics of six active ingredients in four sunscreen formulations, including avobenzone and BP-3. The researchers found that all ingredients were systemically absorbed, with plasma concentrations exceeding the Food and Drug Administration threshold for considering the waiving of further safety studies. They concluded that these results did not warrant discontinuing the use of the tested sunscreen ingredients.8 Yeager and Lim add that, while BP-3 has been incorporated into sunscreen formulations for sale in the United States since 1978, there have been no reports of adverse systemic reactions in human beings.3
However, topical reactions have elicited a different assessment. That is, in 2014, the American Contact Dermatitis Society labeled BPs the Contact Allergen of the Year, as they were identified as the most common source of photoallergic and contact allergic reactions of all UV filters.3,9
Risks of BPs in sunscreens and other skincare products
In 2015, Amar et al. investigated the photogenotoxicity and apoptotic effects in human keratinocytes (HaCaT cells) of BP-1, which is used as a UV blocker in sunscreens. They found that BP-1, when exposed to UV radiation, photosensitized cells and yielded intracellular reactive oxygen species. Significant reductions in cell viability were also seen with exposure to sunlight, UVA, and UVB. The researchers also confirmed genotoxic activity, with BP-1 augmenting lipid peroxidation and upregulating apoptotic proteins. They concluded that sunscreen users should be advised to avoid products that contain BP-1.10
In 2019, Amar et al. evaluated the effects of BPs on the differential expression of proteins in HaCaT cells exposed to UVA. Their findings indicated the expression of novel proteins that helped to initiate or promote apoptosis. They concluded that, because of the predilection to render such effects in human skin keratinocytes, consumers should avoid the use of sunscreens that contain BPs as UV blocking ingredients.11
Still widely used as an effective filter against UVA2 and UVB, BP-3 was believed to be present in two thirds of nonmineral sunscreens in the United States in 2018.3,12
Notably, BP-1 and BP-3 were found in small proportions (3.7% and 4.9%, respectively) among a total of 283 products culled from various stores in Lecce, Italy, in a survey of the potentially dangerous chemicals found in rinse-off, leave-on, and makeup products in 2019.13 The authors added that the International Agency for Research on Cancer, in 2010, classified BP as potentially carcinogenic to humans (2B group).13,14
Promising use of nanocapsules
The widespread concern about the phototoxicity of BP has prompted some interesting research into workarounds. Specifically, in 2019, Barbosa et al. reported on the creation of a new sunscreen formulation using polymeric nanocapsules loading BP-3. The nanocapsules are made of poly(ε-caprolactone) carrot oil and Pluronic F68 (nonionic surfactant used in suspension cultures), and the BP-3–loaded capsules were found to be noncytotoxic in L929 fibroblast cell lines with a sun protection factor of 8.64. The researchers concluded that this promising nanocapsule may be an effective and safe way to use lipophilic sunscreen ingredients such as BP-3.15
Conclusion
The body of evidence is weighted against the use of BPs. Luckily, we have safe sunscreen choices that allow us to protect our skin without using these compounds.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.
References
1. Utsunomiya H et al. Chem Biol Interact. 2019 Jan 25;298:52-6.
2. Schneider SL and Lim HW. J Am Acad Dermatol. 2019 Jan;80(1):266-71.
3. Yeager DG and Lim HW. Dermatol Clin. 2019 Apr;37(2):149-57.
4. Ramos S et al. Sci Total Environ. 2015 Sep 1;526:278-311.
5. Siller A et al. Plast Surg Nur. 2019 Oct/Dec;39(4):157-60.
6. Krause M et al. Int J Androl. 2012 Jun;35(3):424-36.
7. Wang J and Ganley CJ. Clin Pharmacol Ther. 2019 Jan;105(1):161-7.
8. Matta MK et al. JAMA. 2020 Jan 21;323(3):256-67.
9. Warshaw EM et al. Dermatitis. 2013 Jul-Aug;24(4):176-82.
10. Amar SK et al. Toxicol Lett. 2015 Dec 15;239(3):182-93.
11. Amar SK et al. Toxicol Ind Health. 2019 Jul;35(7):457-65.
12. EWG. The trouble with ingredients in sunscreens. Accessed on 4 April 2020.
13. Panico A et al. J Prev Med Hyg. 2019 Mar 29;60(1):E50-7.
14. International Agency for Research on Cancer (IARC). Benzophenone. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. WHO, IARC Press, Lyon, France. 2010;101:285-304.
15. Barbosa TC et al. Toxics. 2019 Sep 22;7(4):51.
The science of clean skin care and the clean beauty movement
. I see numerous social media posts, blogs, and magazine articles about toxic skin care ingredients, while more patients are asking their dermatologists about clean beauty products. So, I decided it was time to dissect the issues and figure out what “clean” really means to me.
The problem is that no one agrees on a clean ingredient standard for beauty products. Many companies, like Target, Walgreens/Boots, Sephora, Neiman Marcus, Whole Foods, and Ulta, have their own varying clean standards. Even Allure magazine has a “Clean Best of Beauty” seal. California has Proposition 65, otherwise known as the Safe Drinking Water and Toxic Enforcement Act of 1986, which contains a list of banned chemicals “known to the state to cause cancer or reproductive toxicity.” In January 2021, Hawai‘i law prohibited the sale of oxybenzone and octinoxate in sunscreens in response to scientific studies showing that these ingredients “are toxic to corals and other marine life.” The Environmental Working Group (EWG) rates the safety of ingredients based on carcinogenicity, developmental and reproductive toxicity, allergenicity, and immunotoxicity. The Cosmetic Ingredient Review (CIR), funded by the Personal Care Products Council, consists of a seven-member steering committee that has at least one dermatologist representing the American Academy of Dermatology and a toxicologist representing the Society of Toxicology. The CIR publishes detailed reviews of ingredients that can be easily found on PubMed and Google Scholar and closely reviews animal and human data and reports on safety and contact dermatitis risk.
Which clean beauty standard is best?
I reviewed most of the various standards, clean seals, laws, and safety reports and found significant discrepancies resulting from misunderstandings of the science, lack of depth in the scientific evaluations, lumping of ingredients into a larger category, or lack of data. The most salient cause of misinformation and confusion seems to be hyperbolic claims by the media and clean beauty advocates who do not understand the basic science.
When I conducted a survey of cosmetic chemists on my LinkedIn account, most of the chemists stated that “ ‘Clean Beauty’ is a marketing term, more than a scientific term.” None of the chemists could give an exact definition of clean beauty. However, I thought I needed a good answer for my patients and for doctors who want to use and recommend “clean skin care brands.”
A dermatologist’s approach to develop a clean beauty standard
Many of the standards combine all of the following into the “clean” designation: nontoxic to the environment (both the production process and the resulting ingredient), nontoxic to marine life and coral, cruelty-free (not tested on animals), hypoallergenic, lacking in known health risks (carcinogenicity, reproductive toxicity), vegan, and gluten free. As a dermatologist, I am a splitter more than a lumper, so I prefer that “clean” be split into categories to make it easier to understand. With that in mind, I will focus on clean beauty ingredients only as they pertain to health: carcinogenicity, endocrine effects, nephrotoxicity, hepatotoxicity, immunotoxicity, etc. This discussion will not consider environmental effects, reproductive toxicity (some ingredients may decrease fertility, which is beyond the scope of this article), ingredient sources, and sustainability, animal testing, or human rights violations during production. Those issues are important, of course, but for clarity and simplicity, we will focus on the health risks of skin care ingredients.
In this month’s column, I will focus on a few ingredients and will continue the discussion in subsequent columns. Please note that commercial standards such as Target standards are based on the product type (e.g., cleansers, sunscreens, or moisturizers). So, when I mention an ingredient not allowed by certain company standards, note that it can vary by product type. My comments pertain mostly to facial moisturizers and facial serums to try and simplify the information. The Good Face Project has a complete list of standards by product type, which I recommend as a resource if you want more detailed information.
Are ethanolamines safe or toxic in cosmetics?
Ethanolamines are common ingredients in surfactants, fragrances, and emulsifying agents and include cocamide diethanolamine (DEA), cocamide monoethanolamine (MEA), and triethanolamine (TEA). Cocamide DEA, lauramide DEA, linoleamide DEA, and oleamide DEA are fatty acid diethanolamides that may contain 4% to 33% diethanolamine.1 A Google search of toxic ingredients in beauty products consistently identifies ethanolamines among such offending product constituents. Table 1 reveals that ethanolamines are excluded from some standards and included in others (N = not allowed or restricted by amount used and Y = allowed with no restrictions). As you can see, the standards don’t correspond to the EWG rating of the ingredients, which ranges from 1 (low hazard) to 10 (high hazard).
Why are ethanolamines sometimes considered safe and sometimes not?
Ethanolamines are reputed to be allergenic, but as we know as dermatologists, that does not mean that everyone will react to them. (In my opinion, allergenicity is a separate issue than the clean issue.) One study showed that TEA in 2.5% petrolatum had a 0.4% positive patch test rate in humans, which was thought to be related more to irritation than allergenicity.2 Cocamide DEA allergy is seen in those with hand dermatitis resulting from hand cleansers but is more commonly seen in metal workers.3 For this reason, these ethanolamines are usually found in rinse-off products to decrease exposure time. But there are many irritating ingredients not banned by Target, Sephora, and Ulta, so why does ethanolamine end up on toxic ingredient lists?
First, there is the issue of oral studies in animals. Oral forms of some ethanolamines have shown mild toxicity in rats, but topical forms have not been demonstrated to cause mutagenicity.1
For this reason, ethanolamines in their native form are considered safe.
The main issue with ethanolamines is that, when they are formulated with ingredients that break down into nitrogen, such as certain preservatives, the combination forms nitrosamines, such as N-nitrosodiethylamine (NDEA), which are carcinogenic.4 The European Commission prohibits DEA in cosmetics based on concerns about formation of these carcinogenic nitrosamines. Some standards limit ethanolamines to rinse-off products.5 The CIR panel concluded that diethanolamine and its 16 salts are safe if they are not used in cosmetic products in which N-nitroso compounds can be formed and that TEA and TEA-related compounds are safe if they are not used in cosmetic products in which N-nitroso compounds can be formed.6,7 The FDA states that there is no reason for consumers to be alarmed based on the use of DEA in cosmetics.8
The safety issues surrounding the use of ethanolamines in a skin care routine illustrate an important point: Every single product in the skin care routine should be compatible with the other products in the regimen. Using ethanolamines in a rinse-off product is one solution, as is ensuring that no other products in the skin care routine contain N-nitroso compounds that can combine with ethanolamines to form nitrosamines.
Are natural products safer?
Natural products are not necessarily any safer than synthetic products. Considering ethanolamines as the example here, note that cocamide DEA is an ethanolamine derived from coconut. It is often found in “green” or “natural” skin care products.9 It can still combine with N-nitroso compounds to form carcinogenic nitrosamines.
What is the bottom line? Are ethanolamines safe in cosmetics?
For now, if a patient asks if ethanolamine is safe in skin care, my answer would be yes, so long as the following is true:
- It is in a rinse-off product.
- The patient is not allergic to it.
- They do not have hand dermatitis.
- Their skin care routine does not include nitrogen-containing compounds like N-nitrosodiethanolamine (NDELA) or NDEA.
Conclusion
This column uses ethanolamines as an example to show the disparity in clean standards in the cosmetic industry. As you can see, there are multiple factors to consider. I will begin including clean information in my cosmeceutical critique columns to address some of these issues.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.
References
1. Cocamide DE. J Am Coll Toxicol. 1986;5(5).
2. Lessmann H et al. Contact Dermatitis. 2009 May;60(5):243-55.
3. Aalto-Korte K et al. 2014 Mar;70(3):169-74.
4. Kraeling ME et al. Food Chem Toxicol. 2004 Oct;42(10):1553-61.
5. Fiume MM et al. Int J Toxicol. 2015 Sep;34(2 Suppl):84S-98S.
6. Fiume MM.. Int J Toxicol. 2017 Sep/Oct;36(5_suppl2):89S-110S.
7. Fiume MM et al. Int J Toxicol. 2013 May-Jun;32(3 Suppl):59S-83S.
8. U.S. Food & Drug Administration. Diethanolamine. https://www.fda.gov/cosmetics/cosmetic-ingredients/diethanolamine. Accessed Feb. 12, 2022.
9. Aryanti N et al. IOP Conference Series: Materials Science and Engineering 2021 Feb 1 (Vol. 1053, No. 1, p. 012066). IOP Publishing.
. I see numerous social media posts, blogs, and magazine articles about toxic skin care ingredients, while more patients are asking their dermatologists about clean beauty products. So, I decided it was time to dissect the issues and figure out what “clean” really means to me.
The problem is that no one agrees on a clean ingredient standard for beauty products. Many companies, like Target, Walgreens/Boots, Sephora, Neiman Marcus, Whole Foods, and Ulta, have their own varying clean standards. Even Allure magazine has a “Clean Best of Beauty” seal. California has Proposition 65, otherwise known as the Safe Drinking Water and Toxic Enforcement Act of 1986, which contains a list of banned chemicals “known to the state to cause cancer or reproductive toxicity.” In January 2021, Hawai‘i law prohibited the sale of oxybenzone and octinoxate in sunscreens in response to scientific studies showing that these ingredients “are toxic to corals and other marine life.” The Environmental Working Group (EWG) rates the safety of ingredients based on carcinogenicity, developmental and reproductive toxicity, allergenicity, and immunotoxicity. The Cosmetic Ingredient Review (CIR), funded by the Personal Care Products Council, consists of a seven-member steering committee that has at least one dermatologist representing the American Academy of Dermatology and a toxicologist representing the Society of Toxicology. The CIR publishes detailed reviews of ingredients that can be easily found on PubMed and Google Scholar and closely reviews animal and human data and reports on safety and contact dermatitis risk.
Which clean beauty standard is best?
I reviewed most of the various standards, clean seals, laws, and safety reports and found significant discrepancies resulting from misunderstandings of the science, lack of depth in the scientific evaluations, lumping of ingredients into a larger category, or lack of data. The most salient cause of misinformation and confusion seems to be hyperbolic claims by the media and clean beauty advocates who do not understand the basic science.
When I conducted a survey of cosmetic chemists on my LinkedIn account, most of the chemists stated that “ ‘Clean Beauty’ is a marketing term, more than a scientific term.” None of the chemists could give an exact definition of clean beauty. However, I thought I needed a good answer for my patients and for doctors who want to use and recommend “clean skin care brands.”
A dermatologist’s approach to develop a clean beauty standard
Many of the standards combine all of the following into the “clean” designation: nontoxic to the environment (both the production process and the resulting ingredient), nontoxic to marine life and coral, cruelty-free (not tested on animals), hypoallergenic, lacking in known health risks (carcinogenicity, reproductive toxicity), vegan, and gluten free. As a dermatologist, I am a splitter more than a lumper, so I prefer that “clean” be split into categories to make it easier to understand. With that in mind, I will focus on clean beauty ingredients only as they pertain to health: carcinogenicity, endocrine effects, nephrotoxicity, hepatotoxicity, immunotoxicity, etc. This discussion will not consider environmental effects, reproductive toxicity (some ingredients may decrease fertility, which is beyond the scope of this article), ingredient sources, and sustainability, animal testing, or human rights violations during production. Those issues are important, of course, but for clarity and simplicity, we will focus on the health risks of skin care ingredients.
In this month’s column, I will focus on a few ingredients and will continue the discussion in subsequent columns. Please note that commercial standards such as Target standards are based on the product type (e.g., cleansers, sunscreens, or moisturizers). So, when I mention an ingredient not allowed by certain company standards, note that it can vary by product type. My comments pertain mostly to facial moisturizers and facial serums to try and simplify the information. The Good Face Project has a complete list of standards by product type, which I recommend as a resource if you want more detailed information.
Are ethanolamines safe or toxic in cosmetics?
Ethanolamines are common ingredients in surfactants, fragrances, and emulsifying agents and include cocamide diethanolamine (DEA), cocamide monoethanolamine (MEA), and triethanolamine (TEA). Cocamide DEA, lauramide DEA, linoleamide DEA, and oleamide DEA are fatty acid diethanolamides that may contain 4% to 33% diethanolamine.1 A Google search of toxic ingredients in beauty products consistently identifies ethanolamines among such offending product constituents. Table 1 reveals that ethanolamines are excluded from some standards and included in others (N = not allowed or restricted by amount used and Y = allowed with no restrictions). As you can see, the standards don’t correspond to the EWG rating of the ingredients, which ranges from 1 (low hazard) to 10 (high hazard).
Why are ethanolamines sometimes considered safe and sometimes not?
Ethanolamines are reputed to be allergenic, but as we know as dermatologists, that does not mean that everyone will react to them. (In my opinion, allergenicity is a separate issue than the clean issue.) One study showed that TEA in 2.5% petrolatum had a 0.4% positive patch test rate in humans, which was thought to be related more to irritation than allergenicity.2 Cocamide DEA allergy is seen in those with hand dermatitis resulting from hand cleansers but is more commonly seen in metal workers.3 For this reason, these ethanolamines are usually found in rinse-off products to decrease exposure time. But there are many irritating ingredients not banned by Target, Sephora, and Ulta, so why does ethanolamine end up on toxic ingredient lists?
First, there is the issue of oral studies in animals. Oral forms of some ethanolamines have shown mild toxicity in rats, but topical forms have not been demonstrated to cause mutagenicity.1
For this reason, ethanolamines in their native form are considered safe.
The main issue with ethanolamines is that, when they are formulated with ingredients that break down into nitrogen, such as certain preservatives, the combination forms nitrosamines, such as N-nitrosodiethylamine (NDEA), which are carcinogenic.4 The European Commission prohibits DEA in cosmetics based on concerns about formation of these carcinogenic nitrosamines. Some standards limit ethanolamines to rinse-off products.5 The CIR panel concluded that diethanolamine and its 16 salts are safe if they are not used in cosmetic products in which N-nitroso compounds can be formed and that TEA and TEA-related compounds are safe if they are not used in cosmetic products in which N-nitroso compounds can be formed.6,7 The FDA states that there is no reason for consumers to be alarmed based on the use of DEA in cosmetics.8
The safety issues surrounding the use of ethanolamines in a skin care routine illustrate an important point: Every single product in the skin care routine should be compatible with the other products in the regimen. Using ethanolamines in a rinse-off product is one solution, as is ensuring that no other products in the skin care routine contain N-nitroso compounds that can combine with ethanolamines to form nitrosamines.
Are natural products safer?
Natural products are not necessarily any safer than synthetic products. Considering ethanolamines as the example here, note that cocamide DEA is an ethanolamine derived from coconut. It is often found in “green” or “natural” skin care products.9 It can still combine with N-nitroso compounds to form carcinogenic nitrosamines.
What is the bottom line? Are ethanolamines safe in cosmetics?
For now, if a patient asks if ethanolamine is safe in skin care, my answer would be yes, so long as the following is true:
- It is in a rinse-off product.
- The patient is not allergic to it.
- They do not have hand dermatitis.
- Their skin care routine does not include nitrogen-containing compounds like N-nitrosodiethanolamine (NDELA) or NDEA.
Conclusion
This column uses ethanolamines as an example to show the disparity in clean standards in the cosmetic industry. As you can see, there are multiple factors to consider. I will begin including clean information in my cosmeceutical critique columns to address some of these issues.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.
References
1. Cocamide DE. J Am Coll Toxicol. 1986;5(5).
2. Lessmann H et al. Contact Dermatitis. 2009 May;60(5):243-55.
3. Aalto-Korte K et al. 2014 Mar;70(3):169-74.
4. Kraeling ME et al. Food Chem Toxicol. 2004 Oct;42(10):1553-61.
5. Fiume MM et al. Int J Toxicol. 2015 Sep;34(2 Suppl):84S-98S.
6. Fiume MM.. Int J Toxicol. 2017 Sep/Oct;36(5_suppl2):89S-110S.
7. Fiume MM et al. Int J Toxicol. 2013 May-Jun;32(3 Suppl):59S-83S.
8. U.S. Food & Drug Administration. Diethanolamine. https://www.fda.gov/cosmetics/cosmetic-ingredients/diethanolamine. Accessed Feb. 12, 2022.
9. Aryanti N et al. IOP Conference Series: Materials Science and Engineering 2021 Feb 1 (Vol. 1053, No. 1, p. 012066). IOP Publishing.
. I see numerous social media posts, blogs, and magazine articles about toxic skin care ingredients, while more patients are asking their dermatologists about clean beauty products. So, I decided it was time to dissect the issues and figure out what “clean” really means to me.
The problem is that no one agrees on a clean ingredient standard for beauty products. Many companies, like Target, Walgreens/Boots, Sephora, Neiman Marcus, Whole Foods, and Ulta, have their own varying clean standards. Even Allure magazine has a “Clean Best of Beauty” seal. California has Proposition 65, otherwise known as the Safe Drinking Water and Toxic Enforcement Act of 1986, which contains a list of banned chemicals “known to the state to cause cancer or reproductive toxicity.” In January 2021, Hawai‘i law prohibited the sale of oxybenzone and octinoxate in sunscreens in response to scientific studies showing that these ingredients “are toxic to corals and other marine life.” The Environmental Working Group (EWG) rates the safety of ingredients based on carcinogenicity, developmental and reproductive toxicity, allergenicity, and immunotoxicity. The Cosmetic Ingredient Review (CIR), funded by the Personal Care Products Council, consists of a seven-member steering committee that has at least one dermatologist representing the American Academy of Dermatology and a toxicologist representing the Society of Toxicology. The CIR publishes detailed reviews of ingredients that can be easily found on PubMed and Google Scholar and closely reviews animal and human data and reports on safety and contact dermatitis risk.
Which clean beauty standard is best?
I reviewed most of the various standards, clean seals, laws, and safety reports and found significant discrepancies resulting from misunderstandings of the science, lack of depth in the scientific evaluations, lumping of ingredients into a larger category, or lack of data. The most salient cause of misinformation and confusion seems to be hyperbolic claims by the media and clean beauty advocates who do not understand the basic science.
When I conducted a survey of cosmetic chemists on my LinkedIn account, most of the chemists stated that “ ‘Clean Beauty’ is a marketing term, more than a scientific term.” None of the chemists could give an exact definition of clean beauty. However, I thought I needed a good answer for my patients and for doctors who want to use and recommend “clean skin care brands.”
A dermatologist’s approach to develop a clean beauty standard
Many of the standards combine all of the following into the “clean” designation: nontoxic to the environment (both the production process and the resulting ingredient), nontoxic to marine life and coral, cruelty-free (not tested on animals), hypoallergenic, lacking in known health risks (carcinogenicity, reproductive toxicity), vegan, and gluten free. As a dermatologist, I am a splitter more than a lumper, so I prefer that “clean” be split into categories to make it easier to understand. With that in mind, I will focus on clean beauty ingredients only as they pertain to health: carcinogenicity, endocrine effects, nephrotoxicity, hepatotoxicity, immunotoxicity, etc. This discussion will not consider environmental effects, reproductive toxicity (some ingredients may decrease fertility, which is beyond the scope of this article), ingredient sources, and sustainability, animal testing, or human rights violations during production. Those issues are important, of course, but for clarity and simplicity, we will focus on the health risks of skin care ingredients.
In this month’s column, I will focus on a few ingredients and will continue the discussion in subsequent columns. Please note that commercial standards such as Target standards are based on the product type (e.g., cleansers, sunscreens, or moisturizers). So, when I mention an ingredient not allowed by certain company standards, note that it can vary by product type. My comments pertain mostly to facial moisturizers and facial serums to try and simplify the information. The Good Face Project has a complete list of standards by product type, which I recommend as a resource if you want more detailed information.
Are ethanolamines safe or toxic in cosmetics?
Ethanolamines are common ingredients in surfactants, fragrances, and emulsifying agents and include cocamide diethanolamine (DEA), cocamide monoethanolamine (MEA), and triethanolamine (TEA). Cocamide DEA, lauramide DEA, linoleamide DEA, and oleamide DEA are fatty acid diethanolamides that may contain 4% to 33% diethanolamine.1 A Google search of toxic ingredients in beauty products consistently identifies ethanolamines among such offending product constituents. Table 1 reveals that ethanolamines are excluded from some standards and included in others (N = not allowed or restricted by amount used and Y = allowed with no restrictions). As you can see, the standards don’t correspond to the EWG rating of the ingredients, which ranges from 1 (low hazard) to 10 (high hazard).
Why are ethanolamines sometimes considered safe and sometimes not?
Ethanolamines are reputed to be allergenic, but as we know as dermatologists, that does not mean that everyone will react to them. (In my opinion, allergenicity is a separate issue than the clean issue.) One study showed that TEA in 2.5% petrolatum had a 0.4% positive patch test rate in humans, which was thought to be related more to irritation than allergenicity.2 Cocamide DEA allergy is seen in those with hand dermatitis resulting from hand cleansers but is more commonly seen in metal workers.3 For this reason, these ethanolamines are usually found in rinse-off products to decrease exposure time. But there are many irritating ingredients not banned by Target, Sephora, and Ulta, so why does ethanolamine end up on toxic ingredient lists?
First, there is the issue of oral studies in animals. Oral forms of some ethanolamines have shown mild toxicity in rats, but topical forms have not been demonstrated to cause mutagenicity.1
For this reason, ethanolamines in their native form are considered safe.
The main issue with ethanolamines is that, when they are formulated with ingredients that break down into nitrogen, such as certain preservatives, the combination forms nitrosamines, such as N-nitrosodiethylamine (NDEA), which are carcinogenic.4 The European Commission prohibits DEA in cosmetics based on concerns about formation of these carcinogenic nitrosamines. Some standards limit ethanolamines to rinse-off products.5 The CIR panel concluded that diethanolamine and its 16 salts are safe if they are not used in cosmetic products in which N-nitroso compounds can be formed and that TEA and TEA-related compounds are safe if they are not used in cosmetic products in which N-nitroso compounds can be formed.6,7 The FDA states that there is no reason for consumers to be alarmed based on the use of DEA in cosmetics.8
The safety issues surrounding the use of ethanolamines in a skin care routine illustrate an important point: Every single product in the skin care routine should be compatible with the other products in the regimen. Using ethanolamines in a rinse-off product is one solution, as is ensuring that no other products in the skin care routine contain N-nitroso compounds that can combine with ethanolamines to form nitrosamines.
Are natural products safer?
Natural products are not necessarily any safer than synthetic products. Considering ethanolamines as the example here, note that cocamide DEA is an ethanolamine derived from coconut. It is often found in “green” or “natural” skin care products.9 It can still combine with N-nitroso compounds to form carcinogenic nitrosamines.
What is the bottom line? Are ethanolamines safe in cosmetics?
For now, if a patient asks if ethanolamine is safe in skin care, my answer would be yes, so long as the following is true:
- It is in a rinse-off product.
- The patient is not allergic to it.
- They do not have hand dermatitis.
- Their skin care routine does not include nitrogen-containing compounds like N-nitrosodiethanolamine (NDELA) or NDEA.
Conclusion
This column uses ethanolamines as an example to show the disparity in clean standards in the cosmetic industry. As you can see, there are multiple factors to consider. I will begin including clean information in my cosmeceutical critique columns to address some of these issues.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.
References
1. Cocamide DE. J Am Coll Toxicol. 1986;5(5).
2. Lessmann H et al. Contact Dermatitis. 2009 May;60(5):243-55.
3. Aalto-Korte K et al. 2014 Mar;70(3):169-74.
4. Kraeling ME et al. Food Chem Toxicol. 2004 Oct;42(10):1553-61.
5. Fiume MM et al. Int J Toxicol. 2015 Sep;34(2 Suppl):84S-98S.
6. Fiume MM.. Int J Toxicol. 2017 Sep/Oct;36(5_suppl2):89S-110S.
7. Fiume MM et al. Int J Toxicol. 2013 May-Jun;32(3 Suppl):59S-83S.
8. U.S. Food & Drug Administration. Diethanolamine. https://www.fda.gov/cosmetics/cosmetic-ingredients/diethanolamine. Accessed Feb. 12, 2022.
9. Aryanti N et al. IOP Conference Series: Materials Science and Engineering 2021 Feb 1 (Vol. 1053, No. 1, p. 012066). IOP Publishing.
Moisturizers and skin barrier repair
There are dozens of skin care products that claim to repair the barrier that do not have the science or ingredient content to back them up.
Does a skin barrier repair moisturizer really repair?
First, let’s briefly review what the skin barrier is. The stratum corneum (SC), the most superficial layer of the epidermis, averages approximately 15-cell layers in thickness.1,2 The keratinocytes reside there in a pattern resembling a brick wall. The “mortar” is composed of the lipid contents extruded from the lamellar granules. This protective barrier functions to prevent transepidermal water loss (TEWL) and entry of allergens, irritants, and pathogens into deeper layers of the skin. This column will focus briefly on the structure and function of the skin barrier and the barrier repair technologies that use synthetic lipids such as myristoyl-palmitoyl and myristyl/palmityl-oxo-stearamide/arachamide MEA.
Structure of the skin barrier
SC keratinocytes are surrounded by lamella made from lipid bilayers. The lipids have hydrophilic heads and hydrophobic tails; the bilayer arises when the hydrophobic tails face the center and the hydrophilic heads face out of the bilayer. This formation yields a disc-shaped hydrophobic lamellar center. There are actually several of these lamellar layers between keratinocytes.
The naturally occurring primary lipids of the bilayer lamellae are made up of an equal ratio of ceramides, cholesterol, and free fatty acid. Arranged in a 1:1:1 ratio, they fit together like pieces of a puzzle to achieve skin barrier homeostasis. The shape and size of these puzzle pieces is critical. An incorrect shape results in a hole in the skin barrier resulting in dehydration, inflammation, and sensitivity.
Ceramides
Ceramides are a complex family of lipids (sphingolipids – a sphingoid base and a fatty acid) involved in cell, as well as barrier, homeostasis and water-holding capacity. In fact, they are known to play a crucial role in cell proliferation, differentiation, and apoptosis.3 There are at least 16 types of naturally occurring ceramides. For years, they have been included in barrier repair moisturizers. They are difficult to work with in moisturizers for several reasons:
- Ceramides are abundant in brain tissue and the ceramides used in moisturizers in the past were derived from bovine brain tissue. Prior to the emergence of bovine spongiform encephalopathy (mad cow disease), many ceramides in skin-care products were animal derived, which made them expensive and undesirable.
- Ceramides in skin care that are made from plant sources are referred to as phyto-derived ceramides. Although they share a similar structure with ceramides that occur in human skin, there are differences in chain length, hydroxylation pattern, and the degree of unsaturation that lead to structural diversity.4 The shape of ceramides is critical for a strong skin barrier because the lipids in the skin barrier must fit together like puzzle pieces to form a water-tight barrier. Natural sources of ceramides include rice, wheat, potato, konjac, and maize. Standardization of ceramide shape and structure makes using phyto-derived ceramides in skin care products challenging.
- Ceramides, because of their waxy consistency, require heat during the mixing process of skin care product manufacturing. This heat can make other ingredients inactive in the skin care formulation. (Ceramides are typically added early in the formulation process, and the heat-sensitive ones are added later.)
- Many forms of ceramides are unstable in the product manufacturing and bottling processes.
- Skin penetration of ceramides depends on the shape and size of ceramides.
Synthetic ceramides have been developed to make ceramides safe, affordable, and more easily formulated into moisturizers. These formulations synthesized in the lab are sometimes called pseudoceramides because they are structurally different compounds that mimic the activity of ceramides. They are developed to be less expensive to manufacture, safer than those derived from animals, and easier to formulate, and they can be made into the specific shape of the ceramide puzzle piece.
Ceramides in skin care
The naturally occurring intercellular lipids of the SC are composed of approximately equal proportions of ceramides, cholesterol, and fatty acids (referred to in this article as the “three barrier lipids” for simplicity).5-9 Alterations in any of these three barrier lipids or their regulatory enzymes result in impairments in the function of the epidermal barrier. Therefore, any synthetic ceramide must mimic the shape of natural ceramides, or the three barrier lipids in the moisturizer must mimic the shape of the entire bilayer lamella. Unfortunately, most barrier repair moisturizers do not meet these criteria and are not true barrier repair moisturizers.
How do you know if a moisturizer repairs the skin barrier?
Clinical tests such as measuring transepidermal water loss (TEWL) with a Tewameter are usually done to support the barrier repair claim. However, occlusive ingredients like oils can lower TEWL without affecting the barrier. In fact, we believe that sebum on the skin can make an impaired barrier and result in normal TEWL even when the barrier is impaired. So, just because a product improved TEWL does not necessarily mean that it repairs the barrier.
One way to test the ability of a moisturizer to repair the barrier is to look at a structural analysis of the moisturizer to see if it forms the requisite bilayer lamellar shape. An easy way to do this testing is to look for the cross pattern under a cross polarized microscope. The cross pattern is known as optical anisotropy. 8
The best barrier repair creams
Optimal barrier repair creams either feature a 1:1:1 ratio of epidermal lipids or form a cross structure when viewed with a cross-polarized microscope.8 There are several categories of barrier repair moisturizers that meet these criteria.
Barrier repair creams with a 1:1:1 ratio of lipids:
Peter Elias, MD, holds the patent on barrier repair moisturizer technology that has a 1:1:1 ratio. His well-established technology is used in a prescription barrier repair cream called EpiCeram® which is approved by the Food and Drug Administration to treat eczema. There are no other moisturizers that I know of that contain this 1:1:1 lipid ratio.
There is a barrier repair cream on the market that contains a 2:4:2 ratio of lipids based on a study that showed that this ratio is effective in older skin with an impaired barrier. It is unknown if this moisturizer forms a cross pattern.
Barrier repair creams that demonstrate a cross pattern:
Multilamellar emulsion (MLE) technology: This barrier repair technology, invented in South Korea, contains the synthetic pseudoceramide called myristyl/palmityl-oxo-stearamide/arachamide MEA (C34H67NO3/C36H71NO3/C38H75NO3), or the pseudoceramide myristoyl-palmitoyl-oxostearamide-arachamide MEA.
In a 2019 pilot study by Ye and colleagues, the investigators treated 33 older volunteers twice daily for 30 days with approximately 3 mL of an emollient containing MLE technology. In addition, 30 untreated older subjects and 11 young volunteers served as controls. The investigators found that the topically applied barrier repair emollient significantly improved barrier function, as well as stratum corneum hydration. Circulating levels of the important, age-related plasma cytokines interleukin-1 beta and IL-6 were found to have normalized, while tumor necrosis factor–alpha decreased markedly. The investigators suggested that repair of the skin barrier might diminish circulating proinflammatory cytokine levels (such as amyloid A) in aged humans, potentially mitigating the development of chronic inflammatory conditions.10
MLE technology has also been shown to improve childhood atopic dermatitis and prevent steroid atrophy.11,12 The consistent use of MLE technology in moisturizers has been shown to alleviate inflammatory factors in the blood and is believed to lessen systemic inflammation.10
Physiologic (PSL) lipid repair technology: This technology was invented by one of the South Korean researchers who helped develop MLE technology. It contains pseudoceramides, fatty acids, and cholesterol. The figure of the cross pattern above, as seen under the cross polarized microscope, is an image taken of this PSL lipid repair technology.
Conclusion
Do not believe that a moisturizer repairs the barrier just because it says so on the label. Three of the most popular body moisturizes used to treat eczema do not actually have the proper formula to repair the barrier. Unfortunately, there are dozens of skin care products that claim to repair the barrier that do not have the science or ingredient content to back them up. To restore the skin barrier to a healthy condition, it is imperative that the barrier repair moisturizers that you are recommending for patients have the correct 1:1:1 ratio of epidermal lipids or contain bilayer lamella that mimic the natural multilamellar layers and display the cross pattern under a cross-polarized microscope.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions, a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.
References
1. Christophers E and Kligman AM. J Invest Dermatol. 1964;42:407-9.
2. Blair C. Br J Dermatol. 1968;80(7):430-6.
3. Morita O et al. Food Chem Toxicol. 2009 Apr;47(4):681-6.
4. Tessema E N et al. Skin pharmacology and physiology. 2017;30(3):115-38.
5. Coderch L et al. Am J Clin Dermatol. 2003;4(2):107-29.
6. Man MQ et al. Arch Dermatol. 1993;129(6):728-38.
7. Man MQ M et al. J Invest Dermatol. 1996 May;106(5):1096-101.
8. Park BD et al. J Invest Dermatol. 2003;121(4):794-801.
9. Proksch E and Jensen J. Skin as an organ of protection, in “Fitzpatrick’s Dermatology in General Medicine,” 7th ed. New York: McGraw-Hill, 2008, pp. 383-95.
10. Ye L et al. J Eur Acad Dermatol Venereol. 2019;33(11):2197-201.
11. Lee EJ et al. Ann Dermatol. 2003;15(4):133-8.
12. Ahn SK et al. J Dermatol. 2006;33(2):80-90.
There are dozens of skin care products that claim to repair the barrier that do not have the science or ingredient content to back them up.
Does a skin barrier repair moisturizer really repair?
First, let’s briefly review what the skin barrier is. The stratum corneum (SC), the most superficial layer of the epidermis, averages approximately 15-cell layers in thickness.1,2 The keratinocytes reside there in a pattern resembling a brick wall. The “mortar” is composed of the lipid contents extruded from the lamellar granules. This protective barrier functions to prevent transepidermal water loss (TEWL) and entry of allergens, irritants, and pathogens into deeper layers of the skin. This column will focus briefly on the structure and function of the skin barrier and the barrier repair technologies that use synthetic lipids such as myristoyl-palmitoyl and myristyl/palmityl-oxo-stearamide/arachamide MEA.
Structure of the skin barrier
SC keratinocytes are surrounded by lamella made from lipid bilayers. The lipids have hydrophilic heads and hydrophobic tails; the bilayer arises when the hydrophobic tails face the center and the hydrophilic heads face out of the bilayer. This formation yields a disc-shaped hydrophobic lamellar center. There are actually several of these lamellar layers between keratinocytes.
The naturally occurring primary lipids of the bilayer lamellae are made up of an equal ratio of ceramides, cholesterol, and free fatty acid. Arranged in a 1:1:1 ratio, they fit together like pieces of a puzzle to achieve skin barrier homeostasis. The shape and size of these puzzle pieces is critical. An incorrect shape results in a hole in the skin barrier resulting in dehydration, inflammation, and sensitivity.
Ceramides
Ceramides are a complex family of lipids (sphingolipids – a sphingoid base and a fatty acid) involved in cell, as well as barrier, homeostasis and water-holding capacity. In fact, they are known to play a crucial role in cell proliferation, differentiation, and apoptosis.3 There are at least 16 types of naturally occurring ceramides. For years, they have been included in barrier repair moisturizers. They are difficult to work with in moisturizers for several reasons:
- Ceramides are abundant in brain tissue and the ceramides used in moisturizers in the past were derived from bovine brain tissue. Prior to the emergence of bovine spongiform encephalopathy (mad cow disease), many ceramides in skin-care products were animal derived, which made them expensive and undesirable.
- Ceramides in skin care that are made from plant sources are referred to as phyto-derived ceramides. Although they share a similar structure with ceramides that occur in human skin, there are differences in chain length, hydroxylation pattern, and the degree of unsaturation that lead to structural diversity.4 The shape of ceramides is critical for a strong skin barrier because the lipids in the skin barrier must fit together like puzzle pieces to form a water-tight barrier. Natural sources of ceramides include rice, wheat, potato, konjac, and maize. Standardization of ceramide shape and structure makes using phyto-derived ceramides in skin care products challenging.
- Ceramides, because of their waxy consistency, require heat during the mixing process of skin care product manufacturing. This heat can make other ingredients inactive in the skin care formulation. (Ceramides are typically added early in the formulation process, and the heat-sensitive ones are added later.)
- Many forms of ceramides are unstable in the product manufacturing and bottling processes.
- Skin penetration of ceramides depends on the shape and size of ceramides.
Synthetic ceramides have been developed to make ceramides safe, affordable, and more easily formulated into moisturizers. These formulations synthesized in the lab are sometimes called pseudoceramides because they are structurally different compounds that mimic the activity of ceramides. They are developed to be less expensive to manufacture, safer than those derived from animals, and easier to formulate, and they can be made into the specific shape of the ceramide puzzle piece.
Ceramides in skin care
The naturally occurring intercellular lipids of the SC are composed of approximately equal proportions of ceramides, cholesterol, and fatty acids (referred to in this article as the “three barrier lipids” for simplicity).5-9 Alterations in any of these three barrier lipids or their regulatory enzymes result in impairments in the function of the epidermal barrier. Therefore, any synthetic ceramide must mimic the shape of natural ceramides, or the three barrier lipids in the moisturizer must mimic the shape of the entire bilayer lamella. Unfortunately, most barrier repair moisturizers do not meet these criteria and are not true barrier repair moisturizers.
How do you know if a moisturizer repairs the skin barrier?
Clinical tests such as measuring transepidermal water loss (TEWL) with a Tewameter are usually done to support the barrier repair claim. However, occlusive ingredients like oils can lower TEWL without affecting the barrier. In fact, we believe that sebum on the skin can make an impaired barrier and result in normal TEWL even when the barrier is impaired. So, just because a product improved TEWL does not necessarily mean that it repairs the barrier.
One way to test the ability of a moisturizer to repair the barrier is to look at a structural analysis of the moisturizer to see if it forms the requisite bilayer lamellar shape. An easy way to do this testing is to look for the cross pattern under a cross polarized microscope. The cross pattern is known as optical anisotropy. 8
The best barrier repair creams
Optimal barrier repair creams either feature a 1:1:1 ratio of epidermal lipids or form a cross structure when viewed with a cross-polarized microscope.8 There are several categories of barrier repair moisturizers that meet these criteria.
Barrier repair creams with a 1:1:1 ratio of lipids:
Peter Elias, MD, holds the patent on barrier repair moisturizer technology that has a 1:1:1 ratio. His well-established technology is used in a prescription barrier repair cream called EpiCeram® which is approved by the Food and Drug Administration to treat eczema. There are no other moisturizers that I know of that contain this 1:1:1 lipid ratio.
There is a barrier repair cream on the market that contains a 2:4:2 ratio of lipids based on a study that showed that this ratio is effective in older skin with an impaired barrier. It is unknown if this moisturizer forms a cross pattern.
Barrier repair creams that demonstrate a cross pattern:
Multilamellar emulsion (MLE) technology: This barrier repair technology, invented in South Korea, contains the synthetic pseudoceramide called myristyl/palmityl-oxo-stearamide/arachamide MEA (C34H67NO3/C36H71NO3/C38H75NO3), or the pseudoceramide myristoyl-palmitoyl-oxostearamide-arachamide MEA.
In a 2019 pilot study by Ye and colleagues, the investigators treated 33 older volunteers twice daily for 30 days with approximately 3 mL of an emollient containing MLE technology. In addition, 30 untreated older subjects and 11 young volunteers served as controls. The investigators found that the topically applied barrier repair emollient significantly improved barrier function, as well as stratum corneum hydration. Circulating levels of the important, age-related plasma cytokines interleukin-1 beta and IL-6 were found to have normalized, while tumor necrosis factor–alpha decreased markedly. The investigators suggested that repair of the skin barrier might diminish circulating proinflammatory cytokine levels (such as amyloid A) in aged humans, potentially mitigating the development of chronic inflammatory conditions.10
MLE technology has also been shown to improve childhood atopic dermatitis and prevent steroid atrophy.11,12 The consistent use of MLE technology in moisturizers has been shown to alleviate inflammatory factors in the blood and is believed to lessen systemic inflammation.10
Physiologic (PSL) lipid repair technology: This technology was invented by one of the South Korean researchers who helped develop MLE technology. It contains pseudoceramides, fatty acids, and cholesterol. The figure of the cross pattern above, as seen under the cross polarized microscope, is an image taken of this PSL lipid repair technology.
Conclusion
Do not believe that a moisturizer repairs the barrier just because it says so on the label. Three of the most popular body moisturizes used to treat eczema do not actually have the proper formula to repair the barrier. Unfortunately, there are dozens of skin care products that claim to repair the barrier that do not have the science or ingredient content to back them up. To restore the skin barrier to a healthy condition, it is imperative that the barrier repair moisturizers that you are recommending for patients have the correct 1:1:1 ratio of epidermal lipids or contain bilayer lamella that mimic the natural multilamellar layers and display the cross pattern under a cross-polarized microscope.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions, a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.
References
1. Christophers E and Kligman AM. J Invest Dermatol. 1964;42:407-9.
2. Blair C. Br J Dermatol. 1968;80(7):430-6.
3. Morita O et al. Food Chem Toxicol. 2009 Apr;47(4):681-6.
4. Tessema E N et al. Skin pharmacology and physiology. 2017;30(3):115-38.
5. Coderch L et al. Am J Clin Dermatol. 2003;4(2):107-29.
6. Man MQ et al. Arch Dermatol. 1993;129(6):728-38.
7. Man MQ M et al. J Invest Dermatol. 1996 May;106(5):1096-101.
8. Park BD et al. J Invest Dermatol. 2003;121(4):794-801.
9. Proksch E and Jensen J. Skin as an organ of protection, in “Fitzpatrick’s Dermatology in General Medicine,” 7th ed. New York: McGraw-Hill, 2008, pp. 383-95.
10. Ye L et al. J Eur Acad Dermatol Venereol. 2019;33(11):2197-201.
11. Lee EJ et al. Ann Dermatol. 2003;15(4):133-8.
12. Ahn SK et al. J Dermatol. 2006;33(2):80-90.
There are dozens of skin care products that claim to repair the barrier that do not have the science or ingredient content to back them up.
Does a skin barrier repair moisturizer really repair?
First, let’s briefly review what the skin barrier is. The stratum corneum (SC), the most superficial layer of the epidermis, averages approximately 15-cell layers in thickness.1,2 The keratinocytes reside there in a pattern resembling a brick wall. The “mortar” is composed of the lipid contents extruded from the lamellar granules. This protective barrier functions to prevent transepidermal water loss (TEWL) and entry of allergens, irritants, and pathogens into deeper layers of the skin. This column will focus briefly on the structure and function of the skin barrier and the barrier repair technologies that use synthetic lipids such as myristoyl-palmitoyl and myristyl/palmityl-oxo-stearamide/arachamide MEA.
Structure of the skin barrier
SC keratinocytes are surrounded by lamella made from lipid bilayers. The lipids have hydrophilic heads and hydrophobic tails; the bilayer arises when the hydrophobic tails face the center and the hydrophilic heads face out of the bilayer. This formation yields a disc-shaped hydrophobic lamellar center. There are actually several of these lamellar layers between keratinocytes.
The naturally occurring primary lipids of the bilayer lamellae are made up of an equal ratio of ceramides, cholesterol, and free fatty acid. Arranged in a 1:1:1 ratio, they fit together like pieces of a puzzle to achieve skin barrier homeostasis. The shape and size of these puzzle pieces is critical. An incorrect shape results in a hole in the skin barrier resulting in dehydration, inflammation, and sensitivity.
Ceramides
Ceramides are a complex family of lipids (sphingolipids – a sphingoid base and a fatty acid) involved in cell, as well as barrier, homeostasis and water-holding capacity. In fact, they are known to play a crucial role in cell proliferation, differentiation, and apoptosis.3 There are at least 16 types of naturally occurring ceramides. For years, they have been included in barrier repair moisturizers. They are difficult to work with in moisturizers for several reasons:
- Ceramides are abundant in brain tissue and the ceramides used in moisturizers in the past were derived from bovine brain tissue. Prior to the emergence of bovine spongiform encephalopathy (mad cow disease), many ceramides in skin-care products were animal derived, which made them expensive and undesirable.
- Ceramides in skin care that are made from plant sources are referred to as phyto-derived ceramides. Although they share a similar structure with ceramides that occur in human skin, there are differences in chain length, hydroxylation pattern, and the degree of unsaturation that lead to structural diversity.4 The shape of ceramides is critical for a strong skin barrier because the lipids in the skin barrier must fit together like puzzle pieces to form a water-tight barrier. Natural sources of ceramides include rice, wheat, potato, konjac, and maize. Standardization of ceramide shape and structure makes using phyto-derived ceramides in skin care products challenging.
- Ceramides, because of their waxy consistency, require heat during the mixing process of skin care product manufacturing. This heat can make other ingredients inactive in the skin care formulation. (Ceramides are typically added early in the formulation process, and the heat-sensitive ones are added later.)
- Many forms of ceramides are unstable in the product manufacturing and bottling processes.
- Skin penetration of ceramides depends on the shape and size of ceramides.
Synthetic ceramides have been developed to make ceramides safe, affordable, and more easily formulated into moisturizers. These formulations synthesized in the lab are sometimes called pseudoceramides because they are structurally different compounds that mimic the activity of ceramides. They are developed to be less expensive to manufacture, safer than those derived from animals, and easier to formulate, and they can be made into the specific shape of the ceramide puzzle piece.
Ceramides in skin care
The naturally occurring intercellular lipids of the SC are composed of approximately equal proportions of ceramides, cholesterol, and fatty acids (referred to in this article as the “three barrier lipids” for simplicity).5-9 Alterations in any of these three barrier lipids or their regulatory enzymes result in impairments in the function of the epidermal barrier. Therefore, any synthetic ceramide must mimic the shape of natural ceramides, or the three barrier lipids in the moisturizer must mimic the shape of the entire bilayer lamella. Unfortunately, most barrier repair moisturizers do not meet these criteria and are not true barrier repair moisturizers.
How do you know if a moisturizer repairs the skin barrier?
Clinical tests such as measuring transepidermal water loss (TEWL) with a Tewameter are usually done to support the barrier repair claim. However, occlusive ingredients like oils can lower TEWL without affecting the barrier. In fact, we believe that sebum on the skin can make an impaired barrier and result in normal TEWL even when the barrier is impaired. So, just because a product improved TEWL does not necessarily mean that it repairs the barrier.
One way to test the ability of a moisturizer to repair the barrier is to look at a structural analysis of the moisturizer to see if it forms the requisite bilayer lamellar shape. An easy way to do this testing is to look for the cross pattern under a cross polarized microscope. The cross pattern is known as optical anisotropy. 8
The best barrier repair creams
Optimal barrier repair creams either feature a 1:1:1 ratio of epidermal lipids or form a cross structure when viewed with a cross-polarized microscope.8 There are several categories of barrier repair moisturizers that meet these criteria.
Barrier repair creams with a 1:1:1 ratio of lipids:
Peter Elias, MD, holds the patent on barrier repair moisturizer technology that has a 1:1:1 ratio. His well-established technology is used in a prescription barrier repair cream called EpiCeram® which is approved by the Food and Drug Administration to treat eczema. There are no other moisturizers that I know of that contain this 1:1:1 lipid ratio.
There is a barrier repair cream on the market that contains a 2:4:2 ratio of lipids based on a study that showed that this ratio is effective in older skin with an impaired barrier. It is unknown if this moisturizer forms a cross pattern.
Barrier repair creams that demonstrate a cross pattern:
Multilamellar emulsion (MLE) technology: This barrier repair technology, invented in South Korea, contains the synthetic pseudoceramide called myristyl/palmityl-oxo-stearamide/arachamide MEA (C34H67NO3/C36H71NO3/C38H75NO3), or the pseudoceramide myristoyl-palmitoyl-oxostearamide-arachamide MEA.
In a 2019 pilot study by Ye and colleagues, the investigators treated 33 older volunteers twice daily for 30 days with approximately 3 mL of an emollient containing MLE technology. In addition, 30 untreated older subjects and 11 young volunteers served as controls. The investigators found that the topically applied barrier repair emollient significantly improved barrier function, as well as stratum corneum hydration. Circulating levels of the important, age-related plasma cytokines interleukin-1 beta and IL-6 were found to have normalized, while tumor necrosis factor–alpha decreased markedly. The investigators suggested that repair of the skin barrier might diminish circulating proinflammatory cytokine levels (such as amyloid A) in aged humans, potentially mitigating the development of chronic inflammatory conditions.10
MLE technology has also been shown to improve childhood atopic dermatitis and prevent steroid atrophy.11,12 The consistent use of MLE technology in moisturizers has been shown to alleviate inflammatory factors in the blood and is believed to lessen systemic inflammation.10
Physiologic (PSL) lipid repair technology: This technology was invented by one of the South Korean researchers who helped develop MLE technology. It contains pseudoceramides, fatty acids, and cholesterol. The figure of the cross pattern above, as seen under the cross polarized microscope, is an image taken of this PSL lipid repair technology.
Conclusion
Do not believe that a moisturizer repairs the barrier just because it says so on the label. Three of the most popular body moisturizes used to treat eczema do not actually have the proper formula to repair the barrier. Unfortunately, there are dozens of skin care products that claim to repair the barrier that do not have the science or ingredient content to back them up. To restore the skin barrier to a healthy condition, it is imperative that the barrier repair moisturizers that you are recommending for patients have the correct 1:1:1 ratio of epidermal lipids or contain bilayer lamella that mimic the natural multilamellar layers and display the cross pattern under a cross-polarized microscope.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions, a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.
References
1. Christophers E and Kligman AM. J Invest Dermatol. 1964;42:407-9.
2. Blair C. Br J Dermatol. 1968;80(7):430-6.
3. Morita O et al. Food Chem Toxicol. 2009 Apr;47(4):681-6.
4. Tessema E N et al. Skin pharmacology and physiology. 2017;30(3):115-38.
5. Coderch L et al. Am J Clin Dermatol. 2003;4(2):107-29.
6. Man MQ et al. Arch Dermatol. 1993;129(6):728-38.
7. Man MQ M et al. J Invest Dermatol. 1996 May;106(5):1096-101.
8. Park BD et al. J Invest Dermatol. 2003;121(4):794-801.
9. Proksch E and Jensen J. Skin as an organ of protection, in “Fitzpatrick’s Dermatology in General Medicine,” 7th ed. New York: McGraw-Hill, 2008, pp. 383-95.
10. Ye L et al. J Eur Acad Dermatol Venereol. 2019;33(11):2197-201.
11. Lee EJ et al. Ann Dermatol. 2003;15(4):133-8.
12. Ahn SK et al. J Dermatol. 2006;33(2):80-90.
Does the use of frankincense make sense in dermatology?
The Boswellia serrata exudate or gum (known in India as “guggulu”) that forms an aromatic resin traditionally used as incense – and known as frankincense (especially when retrieved from Boswellia species found in Eritrea and Somalia but also from the Indian variety) – has been considered for thousands of years to possess therapeutic properties. It is used in Ayurvedic medicine, as well as in traditional medicine in China and the Middle East, particularly for its anti-inflammatory effects to treat chronic conditions.1-8 In fact, such essential oils have been used since 2800 BC to treat various inflammatory conditions, including skin sores and wounds, as well as in perfumes and incense.2,9 In the West, use of frankincense dates back to thousands of years as well, more often found in the form of incense for religious and cultural ceremonies.7 Over the past 2 decades, .3 This column focuses on some of the emerging data on this ancient botanical agent.
Chemical constituents
Terpenoids and essential oils are the primary components of frankincense and are known to impart anti-inflammatory and anticancer activity. The same is true for myrrh, which has been combined with frankincense in traditional Chinese medicine as a single medication for millennia, with the two acting synergistically and considered still to be a potent combination in conferring various biological benefits.7
In 2010, in a systematic review of the anti-inflammatory and anticancer activities of Boswellia species and their chemical ingredients, Efferth and Oesch found that frankincense blocks the production of leukotrienes, cyclooxygenase (COX) 1 and 2, as well as 5-lipoxygenase; and oxidative stress. It also contributes to regulation of immune cells from the innate and acquired immune systems and exerts anticancer activity by influencing signaling transduction responsible for cell cycle arrest, as well as inhibition of proliferation, angiogenesis, invasion, and metastasis. The investigators also reported on clinical trial results that have found efficacy of frankincense and its constituents in ameliorating symptoms of psoriasis and erythematous eczema, among other disorders.3
Anti-inflammatory activity
Li et al. completed a study in 2016 to identify the active ingredients responsible for the anti-inflammatory and analgesic effects of frankincense. They found that alpha-pinene, linalool, and 1-octanol were key contributors. These constituents were noted for suppressing COX-2 overexpression in mice, as well as nociceptive stimulus-induced inflammatory infiltrates.10
Noting the increasing popularity of frankincense essential oil in skin care, despite a paucity of data, in 2017, Han et al. evaluated the biological activities of the essential oil in pre-inflamed human dermal fibroblasts using 17 key protein biomarkers. Frankincense essential oil displayed significant antiproliferative activity and suppressed collagen III, interferon gamma-induced protein 10, and intracellular adhesion molecule 1. The investigators referred to the overall encouraging potential of frankincense essential oil to exert influence over inflammation and tissue remodeling in human skin and called for additional research into its mechanisms of action and active constituents.11
Anticancer activity
The main active ingredient in frankincense, boswellic acid, has been shown to promote apoptosis, suppress matrix metalloproteinase secretion, and hinder migration in metastatic melanoma cell lines in mice.6,12
In 2019, Hakkim et al. demonstrated that frankincense essential oil yielded substantial antimelanoma activity in vitro and in vivo and ameliorated hepatotoxicity caused by acetaminophen.13
There is one case report in the literature on the use of frankincense as a treatment for skin cancer. A 56-year-old man received frankincense oil multiple times a day for 4 months to treat a nodular basal cell carcinoma on one arm (which resolved) and an infiltrative BCC on the chest (some focal residual tumor remained).6,14 Topical frankincense or boswellic acid has been given a grade D recommendation for treating skin cancer, however, because of only one level-of-evidence-5 study.6
Antimicrobial activity
In 2012, de Rapper et al. collected samples of three essential oils of frankincense (Boswellia rivae, Boswellia neglecta, and Boswellia papyrifera) and two essential oil samples of myrrh and sweet myrrh from different regions of Ethiopia to study their anti-infective properties alone and in combination. The investigators observed synergistic and additive effects, particularly between B. papyrifera and Commiphora myrrha. While noting the long history of the combined use of frankincense and myrrh essential oils since 1500 BC, the investigators highlighted their study as the first antimicrobial work to verify the effectiveness of this combination, validating the use of this combination to thwart particular pathogens.15
Just 2 years ago, Ljaljević Grbić et al. evaluated the in vitro antimicrobial potential of the liquid and vapor phases of B. carteri and C. myrrha (frankincense and myrrh, respectively) essential oils, finding that frankincense demonstrated marked capacity to act as a natural antimicrobial agent.9
Transdermal delivery
In 2017, Zhu et al. showed that frankincense and myrrh essential oils promoted the permeability of the Chinese herb Chuanxiong and may facilitate drug elimination from the epidermis via dermal capillaries by dint of improved cutaneous blood flow, thereby augmenting transdermal drug delivery.16 The same team also showed that frankincense and myrrh essential oils, by fostering permeation by enhancing drug delivery across the stratum corneum, can also alter the structure of the stratum corneum.17
Conclusion
The use of frankincense in traditional medicine has a long and impressive track record. Recent research provides reason for optimism, and further investigating the possible incorporation of this botanical agent into modern dermatologic therapies appears warranted. Clearly, however, much more research is needed.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.
References
1. Kimmatkar N et al. Phytomedicine. 2003 Jan;10(1):3-7.
2. Ammon HP. Wien Med Wochenschr. 2002;152(15-16):373-8.
3. Efferth T & Oesch F. Semin Cancer Biol. 2020 Feb 4;S1044-579X(20)30034-1.
4. Banno N et al. J Ethnopharmacol. 2006 Sep 19;107(2):249-53.
5. Poeckel D & Werz O. Curr Med Chem. 2006;13(28):3359-69.
6. Li JY, Kampp JT. Dermatol Surg. 2019 Jan;45(1):58-67.
7. Cao B et al. Molecules. 2019 Aug 24;24(17): 3076.
8. Mertens M et al. Flavour Fragr J. 2009;24:279-300.
9. Ljaljević Grbić M et al. J Ethnopharmacol. 2018 Jun 12;219:1-14.
10. Li XJ et al. J Ethnopharmacol. 2016 Feb 17;179:22-6.
11. Han X et al. Biochim Open. 2017 Feb 3;4:31-5.
12. Zhao W et al. Cancer Detect Prev. 2003;27:67-75.
13. Hakkim FL et al. Oncotarget. 2019 May 28;10(37):3472-90.
14. Fung K et al. OA Altern Med 2013;1:14.
15. de Rapper S et al. Lett Appl Microbiol. 2012 Apr;54(4):352-8.
16. Zhu XF et al. Zhongguo Zhong Yao Za Zhi. 2017 Feb;42(4):680-5.
17. Guan YM et al. Zhongguo Zhong Yao Za Zhi. 2017 Sep;42(17):3350-5.
The Boswellia serrata exudate or gum (known in India as “guggulu”) that forms an aromatic resin traditionally used as incense – and known as frankincense (especially when retrieved from Boswellia species found in Eritrea and Somalia but also from the Indian variety) – has been considered for thousands of years to possess therapeutic properties. It is used in Ayurvedic medicine, as well as in traditional medicine in China and the Middle East, particularly for its anti-inflammatory effects to treat chronic conditions.1-8 In fact, such essential oils have been used since 2800 BC to treat various inflammatory conditions, including skin sores and wounds, as well as in perfumes and incense.2,9 In the West, use of frankincense dates back to thousands of years as well, more often found in the form of incense for religious and cultural ceremonies.7 Over the past 2 decades, .3 This column focuses on some of the emerging data on this ancient botanical agent.
Chemical constituents
Terpenoids and essential oils are the primary components of frankincense and are known to impart anti-inflammatory and anticancer activity. The same is true for myrrh, which has been combined with frankincense in traditional Chinese medicine as a single medication for millennia, with the two acting synergistically and considered still to be a potent combination in conferring various biological benefits.7
In 2010, in a systematic review of the anti-inflammatory and anticancer activities of Boswellia species and their chemical ingredients, Efferth and Oesch found that frankincense blocks the production of leukotrienes, cyclooxygenase (COX) 1 and 2, as well as 5-lipoxygenase; and oxidative stress. It also contributes to regulation of immune cells from the innate and acquired immune systems and exerts anticancer activity by influencing signaling transduction responsible for cell cycle arrest, as well as inhibition of proliferation, angiogenesis, invasion, and metastasis. The investigators also reported on clinical trial results that have found efficacy of frankincense and its constituents in ameliorating symptoms of psoriasis and erythematous eczema, among other disorders.3
Anti-inflammatory activity
Li et al. completed a study in 2016 to identify the active ingredients responsible for the anti-inflammatory and analgesic effects of frankincense. They found that alpha-pinene, linalool, and 1-octanol were key contributors. These constituents were noted for suppressing COX-2 overexpression in mice, as well as nociceptive stimulus-induced inflammatory infiltrates.10
Noting the increasing popularity of frankincense essential oil in skin care, despite a paucity of data, in 2017, Han et al. evaluated the biological activities of the essential oil in pre-inflamed human dermal fibroblasts using 17 key protein biomarkers. Frankincense essential oil displayed significant antiproliferative activity and suppressed collagen III, interferon gamma-induced protein 10, and intracellular adhesion molecule 1. The investigators referred to the overall encouraging potential of frankincense essential oil to exert influence over inflammation and tissue remodeling in human skin and called for additional research into its mechanisms of action and active constituents.11
Anticancer activity
The main active ingredient in frankincense, boswellic acid, has been shown to promote apoptosis, suppress matrix metalloproteinase secretion, and hinder migration in metastatic melanoma cell lines in mice.6,12
In 2019, Hakkim et al. demonstrated that frankincense essential oil yielded substantial antimelanoma activity in vitro and in vivo and ameliorated hepatotoxicity caused by acetaminophen.13
There is one case report in the literature on the use of frankincense as a treatment for skin cancer. A 56-year-old man received frankincense oil multiple times a day for 4 months to treat a nodular basal cell carcinoma on one arm (which resolved) and an infiltrative BCC on the chest (some focal residual tumor remained).6,14 Topical frankincense or boswellic acid has been given a grade D recommendation for treating skin cancer, however, because of only one level-of-evidence-5 study.6
Antimicrobial activity
In 2012, de Rapper et al. collected samples of three essential oils of frankincense (Boswellia rivae, Boswellia neglecta, and Boswellia papyrifera) and two essential oil samples of myrrh and sweet myrrh from different regions of Ethiopia to study their anti-infective properties alone and in combination. The investigators observed synergistic and additive effects, particularly between B. papyrifera and Commiphora myrrha. While noting the long history of the combined use of frankincense and myrrh essential oils since 1500 BC, the investigators highlighted their study as the first antimicrobial work to verify the effectiveness of this combination, validating the use of this combination to thwart particular pathogens.15
Just 2 years ago, Ljaljević Grbić et al. evaluated the in vitro antimicrobial potential of the liquid and vapor phases of B. carteri and C. myrrha (frankincense and myrrh, respectively) essential oils, finding that frankincense demonstrated marked capacity to act as a natural antimicrobial agent.9
Transdermal delivery
In 2017, Zhu et al. showed that frankincense and myrrh essential oils promoted the permeability of the Chinese herb Chuanxiong and may facilitate drug elimination from the epidermis via dermal capillaries by dint of improved cutaneous blood flow, thereby augmenting transdermal drug delivery.16 The same team also showed that frankincense and myrrh essential oils, by fostering permeation by enhancing drug delivery across the stratum corneum, can also alter the structure of the stratum corneum.17
Conclusion
The use of frankincense in traditional medicine has a long and impressive track record. Recent research provides reason for optimism, and further investigating the possible incorporation of this botanical agent into modern dermatologic therapies appears warranted. Clearly, however, much more research is needed.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.
References
1. Kimmatkar N et al. Phytomedicine. 2003 Jan;10(1):3-7.
2. Ammon HP. Wien Med Wochenschr. 2002;152(15-16):373-8.
3. Efferth T & Oesch F. Semin Cancer Biol. 2020 Feb 4;S1044-579X(20)30034-1.
4. Banno N et al. J Ethnopharmacol. 2006 Sep 19;107(2):249-53.
5. Poeckel D & Werz O. Curr Med Chem. 2006;13(28):3359-69.
6. Li JY, Kampp JT. Dermatol Surg. 2019 Jan;45(1):58-67.
7. Cao B et al. Molecules. 2019 Aug 24;24(17): 3076.
8. Mertens M et al. Flavour Fragr J. 2009;24:279-300.
9. Ljaljević Grbić M et al. J Ethnopharmacol. 2018 Jun 12;219:1-14.
10. Li XJ et al. J Ethnopharmacol. 2016 Feb 17;179:22-6.
11. Han X et al. Biochim Open. 2017 Feb 3;4:31-5.
12. Zhao W et al. Cancer Detect Prev. 2003;27:67-75.
13. Hakkim FL et al. Oncotarget. 2019 May 28;10(37):3472-90.
14. Fung K et al. OA Altern Med 2013;1:14.
15. de Rapper S et al. Lett Appl Microbiol. 2012 Apr;54(4):352-8.
16. Zhu XF et al. Zhongguo Zhong Yao Za Zhi. 2017 Feb;42(4):680-5.
17. Guan YM et al. Zhongguo Zhong Yao Za Zhi. 2017 Sep;42(17):3350-5.
The Boswellia serrata exudate or gum (known in India as “guggulu”) that forms an aromatic resin traditionally used as incense – and known as frankincense (especially when retrieved from Boswellia species found in Eritrea and Somalia but also from the Indian variety) – has been considered for thousands of years to possess therapeutic properties. It is used in Ayurvedic medicine, as well as in traditional medicine in China and the Middle East, particularly for its anti-inflammatory effects to treat chronic conditions.1-8 In fact, such essential oils have been used since 2800 BC to treat various inflammatory conditions, including skin sores and wounds, as well as in perfumes and incense.2,9 In the West, use of frankincense dates back to thousands of years as well, more often found in the form of incense for religious and cultural ceremonies.7 Over the past 2 decades, .3 This column focuses on some of the emerging data on this ancient botanical agent.
Chemical constituents
Terpenoids and essential oils are the primary components of frankincense and are known to impart anti-inflammatory and anticancer activity. The same is true for myrrh, which has been combined with frankincense in traditional Chinese medicine as a single medication for millennia, with the two acting synergistically and considered still to be a potent combination in conferring various biological benefits.7
In 2010, in a systematic review of the anti-inflammatory and anticancer activities of Boswellia species and their chemical ingredients, Efferth and Oesch found that frankincense blocks the production of leukotrienes, cyclooxygenase (COX) 1 and 2, as well as 5-lipoxygenase; and oxidative stress. It also contributes to regulation of immune cells from the innate and acquired immune systems and exerts anticancer activity by influencing signaling transduction responsible for cell cycle arrest, as well as inhibition of proliferation, angiogenesis, invasion, and metastasis. The investigators also reported on clinical trial results that have found efficacy of frankincense and its constituents in ameliorating symptoms of psoriasis and erythematous eczema, among other disorders.3
Anti-inflammatory activity
Li et al. completed a study in 2016 to identify the active ingredients responsible for the anti-inflammatory and analgesic effects of frankincense. They found that alpha-pinene, linalool, and 1-octanol were key contributors. These constituents were noted for suppressing COX-2 overexpression in mice, as well as nociceptive stimulus-induced inflammatory infiltrates.10
Noting the increasing popularity of frankincense essential oil in skin care, despite a paucity of data, in 2017, Han et al. evaluated the biological activities of the essential oil in pre-inflamed human dermal fibroblasts using 17 key protein biomarkers. Frankincense essential oil displayed significant antiproliferative activity and suppressed collagen III, interferon gamma-induced protein 10, and intracellular adhesion molecule 1. The investigators referred to the overall encouraging potential of frankincense essential oil to exert influence over inflammation and tissue remodeling in human skin and called for additional research into its mechanisms of action and active constituents.11
Anticancer activity
The main active ingredient in frankincense, boswellic acid, has been shown to promote apoptosis, suppress matrix metalloproteinase secretion, and hinder migration in metastatic melanoma cell lines in mice.6,12
In 2019, Hakkim et al. demonstrated that frankincense essential oil yielded substantial antimelanoma activity in vitro and in vivo and ameliorated hepatotoxicity caused by acetaminophen.13
There is one case report in the literature on the use of frankincense as a treatment for skin cancer. A 56-year-old man received frankincense oil multiple times a day for 4 months to treat a nodular basal cell carcinoma on one arm (which resolved) and an infiltrative BCC on the chest (some focal residual tumor remained).6,14 Topical frankincense or boswellic acid has been given a grade D recommendation for treating skin cancer, however, because of only one level-of-evidence-5 study.6
Antimicrobial activity
In 2012, de Rapper et al. collected samples of three essential oils of frankincense (Boswellia rivae, Boswellia neglecta, and Boswellia papyrifera) and two essential oil samples of myrrh and sweet myrrh from different regions of Ethiopia to study their anti-infective properties alone and in combination. The investigators observed synergistic and additive effects, particularly between B. papyrifera and Commiphora myrrha. While noting the long history of the combined use of frankincense and myrrh essential oils since 1500 BC, the investigators highlighted their study as the first antimicrobial work to verify the effectiveness of this combination, validating the use of this combination to thwart particular pathogens.15
Just 2 years ago, Ljaljević Grbić et al. evaluated the in vitro antimicrobial potential of the liquid and vapor phases of B. carteri and C. myrrha (frankincense and myrrh, respectively) essential oils, finding that frankincense demonstrated marked capacity to act as a natural antimicrobial agent.9
Transdermal delivery
In 2017, Zhu et al. showed that frankincense and myrrh essential oils promoted the permeability of the Chinese herb Chuanxiong and may facilitate drug elimination from the epidermis via dermal capillaries by dint of improved cutaneous blood flow, thereby augmenting transdermal drug delivery.16 The same team also showed that frankincense and myrrh essential oils, by fostering permeation by enhancing drug delivery across the stratum corneum, can also alter the structure of the stratum corneum.17
Conclusion
The use of frankincense in traditional medicine has a long and impressive track record. Recent research provides reason for optimism, and further investigating the possible incorporation of this botanical agent into modern dermatologic therapies appears warranted. Clearly, however, much more research is needed.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.
References
1. Kimmatkar N et al. Phytomedicine. 2003 Jan;10(1):3-7.
2. Ammon HP. Wien Med Wochenschr. 2002;152(15-16):373-8.
3. Efferth T & Oesch F. Semin Cancer Biol. 2020 Feb 4;S1044-579X(20)30034-1.
4. Banno N et al. J Ethnopharmacol. 2006 Sep 19;107(2):249-53.
5. Poeckel D & Werz O. Curr Med Chem. 2006;13(28):3359-69.
6. Li JY, Kampp JT. Dermatol Surg. 2019 Jan;45(1):58-67.
7. Cao B et al. Molecules. 2019 Aug 24;24(17): 3076.
8. Mertens M et al. Flavour Fragr J. 2009;24:279-300.
9. Ljaljević Grbić M et al. J Ethnopharmacol. 2018 Jun 12;219:1-14.
10. Li XJ et al. J Ethnopharmacol. 2016 Feb 17;179:22-6.
11. Han X et al. Biochim Open. 2017 Feb 3;4:31-5.
12. Zhao W et al. Cancer Detect Prev. 2003;27:67-75.
13. Hakkim FL et al. Oncotarget. 2019 May 28;10(37):3472-90.
14. Fung K et al. OA Altern Med 2013;1:14.
15. de Rapper S et al. Lett Appl Microbiol. 2012 Apr;54(4):352-8.
16. Zhu XF et al. Zhongguo Zhong Yao Za Zhi. 2017 Feb;42(4):680-5.
17. Guan YM et al. Zhongguo Zhong Yao Za Zhi. 2017 Sep;42(17):3350-5.
The tryptophan photoproduct FICZ and its effects on the skin
The melatonin precursor tryptophan, an amino acid essential in the human diet, has been shown to display antioxidant effects.1 FICZ (also known as 6-formylindolo[3,2-b]carbazole) is a photoproduct of tryptophan that is engendered by exposure to UVB.2 This column discusses the beneficial and detrimental influence of FICZ in skin health.
Antioxidant activity
In 2005, Trommer and Neubert devised a skin lipid model system to screen 47 various compounds (drugs, plant extracts, other plant constituents, and polysaccharides) for topical antioxidative activity in response to UV-induced lipid peroxidation. Among the drugs evaluated, they observed that tryptophan exerted antioxidant effects.3
Wound healing potential
A murine study by Bandeira et al. in 2015 revealed that tryptophan-induced mitigation of the inflammatory response and indoleamine 2, 3-dioxygenase expression may have enhanced skin wound healing in mice who were repeatedly stressed.4
Antifibrotic activity
In 2018, Murai et al. endeavored to clarify the role of FICZ in regulating the expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in normal human dermal fibroblasts. They found that FICZ assists in imparting UV-mediated antifibrotic effects through the AHR/MEK/ERK signal pathway in normal human dermal fibroblasts and, thus, shows promise as a therapeutic option for scleroderma.5
Cutaneous leishmaniasis
In 2019, Rodrigues et al. conducted a quantitative analysis of the relative expression of 170 genes involved in various biological processes in the skin biopsies from patients with cutaneous leishmaniasis caused by infection with either Leishmania major or L. tropica. They identified tryptophan-2,3-deoxygenase as a restriction factor for the disorder.6
Photosensitizing activity
Park et al. showed that FICZ, a tryptophan photoproduct and endogenous high-affinity aryl hydrocarbon receptor (AhR) agonist, exhibits nanomolar photodynamic activity as a UVA photosensitizer in epidermal keratinocytes and, thus, is possibly operative in human skin.7 Syed and Mukhtar add that FICZ is effective at nanomolar concentrations and that future research may elucidate its applicability against UV-induced adverse effects and inflammatory skin conditions.8
FICZ, oxidative stress, and cancer promotion
FICZ is known to display detrimental, as well as beneficial, influences in skin. The tryptophan photoproduct, comparable to UVB, ligates AhR, generates reactive oxygen species, and strongly photosensitizes for UVA. As Furue et al. note, FICZ upregulates the expression of terminal differentiation molecules (i.e., filaggrin and loricrin via AhR), and its application has been shown to suppress cutaneous inflammation in a psoriasis and dermatitis mouse model.2
In 2016, Reid et al. reported that the protein photodamage brought about by endogenous photosensitizers such as tryptophan tyrosine residues can contribute to the deleterious impact of UVA on human skin.9
In 2018, Tanaka et al. showed that FICZ imparts a cascade of events tantamount in some cases to UVB, as it promoted the synthesis of proinflammatory cytokines such as interleukin (IL)-1 alpha, IL-1 beta, and IL-6 and boosted reactive oxygen species generation in human HaCaT keratinocytes in an AhR-dependent fashion. They concluded that observing FICZ activity contributes to the understanding of how UVB damages organisms.10
That same year, Murai et al. assessed the effects of FICZ on TGF-beta-mediated ACTA2 and collagen I expression in normal human dermal fibroblasts. They determined that it may act as a key chromophore and one approach to mitigating the effects of photoaging may be to downregulate FICZ signaling.11
A year earlier, Brem et al. showed that the combined effect of FICZ and UVA engendered significant protein damage in HaCaT human keratinocytes, with the oxidation yielded from the combination of FICZ and UVA blocking the removal of potentially mutagenic UVB-induced DNA photolesions by nucleotide excision repair. The researchers concluded that the development of FICZ may raise the risk of incurring skin cancer resulting from sun exposure via the promotion of photochemical impairment of the nucleotide excision repair proteome, which in turn inhibits the removal of UVB-induced DNA lesions.12
Conclusion
However, the tryptophan photoproduct FICZ, which results from UVB exposure, presents as a complicated substance, conferring healthy and harmful effects. Much more research is necessary to determine how best to harness and direct the useful activities of tryptophan and FICZ without incurring damaging effects. Nanotechnology may be one useful avenue of investigation for this purpose.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.
References
1. Trommer H et al. J Pharm Pharmacol. 2003 Oct;55(10):1379-88.
2. Furue M et al. G Ital Dermatol Venereol. 2019 Feb;154(1):37-41.
3. Trommer H and Neubert RH. J Pharm Pharm Sci. 2005 Sep 15;8(3):494-506.
4. Bandeira LG et al. PLoS One. 2015 Jun 9:10(6):e0128439.
5. Murai M et al. J Dermatol Sci. 2018 Jul;91(1):97-103.
6. Rodrigues V et al. Front Cell Infect Microbiol. 2019 Oct 4;9:338. eCollection 2019.
7. Park SL et al. J Invest Dermatol. 2015 Jun;135(6):1649-58.
8. Syed DN and Mukhtar H. J Invest Dermatol. 2015 Jun;135(6):1478-81.
9. Reid LO et al. Biochemistry. 2016 Aug 30;55(34):4777-86.
10. Tanaka Y et al. Oxid Med Cell Longev. 2018 Nov 25;2018:9298052.
11. Murai M et al. J Dermatol Sci. 2018 Jan;89(1):19-26.
12. Brem R et al. Sci Rep. 2017 Jun 27;7(1):4310.
The melatonin precursor tryptophan, an amino acid essential in the human diet, has been shown to display antioxidant effects.1 FICZ (also known as 6-formylindolo[3,2-b]carbazole) is a photoproduct of tryptophan that is engendered by exposure to UVB.2 This column discusses the beneficial and detrimental influence of FICZ in skin health.
Antioxidant activity
In 2005, Trommer and Neubert devised a skin lipid model system to screen 47 various compounds (drugs, plant extracts, other plant constituents, and polysaccharides) for topical antioxidative activity in response to UV-induced lipid peroxidation. Among the drugs evaluated, they observed that tryptophan exerted antioxidant effects.3
Wound healing potential
A murine study by Bandeira et al. in 2015 revealed that tryptophan-induced mitigation of the inflammatory response and indoleamine 2, 3-dioxygenase expression may have enhanced skin wound healing in mice who were repeatedly stressed.4
Antifibrotic activity
In 2018, Murai et al. endeavored to clarify the role of FICZ in regulating the expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in normal human dermal fibroblasts. They found that FICZ assists in imparting UV-mediated antifibrotic effects through the AHR/MEK/ERK signal pathway in normal human dermal fibroblasts and, thus, shows promise as a therapeutic option for scleroderma.5
Cutaneous leishmaniasis
In 2019, Rodrigues et al. conducted a quantitative analysis of the relative expression of 170 genes involved in various biological processes in the skin biopsies from patients with cutaneous leishmaniasis caused by infection with either Leishmania major or L. tropica. They identified tryptophan-2,3-deoxygenase as a restriction factor for the disorder.6
Photosensitizing activity
Park et al. showed that FICZ, a tryptophan photoproduct and endogenous high-affinity aryl hydrocarbon receptor (AhR) agonist, exhibits nanomolar photodynamic activity as a UVA photosensitizer in epidermal keratinocytes and, thus, is possibly operative in human skin.7 Syed and Mukhtar add that FICZ is effective at nanomolar concentrations and that future research may elucidate its applicability against UV-induced adverse effects and inflammatory skin conditions.8
FICZ, oxidative stress, and cancer promotion
FICZ is known to display detrimental, as well as beneficial, influences in skin. The tryptophan photoproduct, comparable to UVB, ligates AhR, generates reactive oxygen species, and strongly photosensitizes for UVA. As Furue et al. note, FICZ upregulates the expression of terminal differentiation molecules (i.e., filaggrin and loricrin via AhR), and its application has been shown to suppress cutaneous inflammation in a psoriasis and dermatitis mouse model.2
In 2016, Reid et al. reported that the protein photodamage brought about by endogenous photosensitizers such as tryptophan tyrosine residues can contribute to the deleterious impact of UVA on human skin.9
In 2018, Tanaka et al. showed that FICZ imparts a cascade of events tantamount in some cases to UVB, as it promoted the synthesis of proinflammatory cytokines such as interleukin (IL)-1 alpha, IL-1 beta, and IL-6 and boosted reactive oxygen species generation in human HaCaT keratinocytes in an AhR-dependent fashion. They concluded that observing FICZ activity contributes to the understanding of how UVB damages organisms.10
That same year, Murai et al. assessed the effects of FICZ on TGF-beta-mediated ACTA2 and collagen I expression in normal human dermal fibroblasts. They determined that it may act as a key chromophore and one approach to mitigating the effects of photoaging may be to downregulate FICZ signaling.11
A year earlier, Brem et al. showed that the combined effect of FICZ and UVA engendered significant protein damage in HaCaT human keratinocytes, with the oxidation yielded from the combination of FICZ and UVA blocking the removal of potentially mutagenic UVB-induced DNA photolesions by nucleotide excision repair. The researchers concluded that the development of FICZ may raise the risk of incurring skin cancer resulting from sun exposure via the promotion of photochemical impairment of the nucleotide excision repair proteome, which in turn inhibits the removal of UVB-induced DNA lesions.12
Conclusion
However, the tryptophan photoproduct FICZ, which results from UVB exposure, presents as a complicated substance, conferring healthy and harmful effects. Much more research is necessary to determine how best to harness and direct the useful activities of tryptophan and FICZ without incurring damaging effects. Nanotechnology may be one useful avenue of investigation for this purpose.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.
References
1. Trommer H et al. J Pharm Pharmacol. 2003 Oct;55(10):1379-88.
2. Furue M et al. G Ital Dermatol Venereol. 2019 Feb;154(1):37-41.
3. Trommer H and Neubert RH. J Pharm Pharm Sci. 2005 Sep 15;8(3):494-506.
4. Bandeira LG et al. PLoS One. 2015 Jun 9:10(6):e0128439.
5. Murai M et al. J Dermatol Sci. 2018 Jul;91(1):97-103.
6. Rodrigues V et al. Front Cell Infect Microbiol. 2019 Oct 4;9:338. eCollection 2019.
7. Park SL et al. J Invest Dermatol. 2015 Jun;135(6):1649-58.
8. Syed DN and Mukhtar H. J Invest Dermatol. 2015 Jun;135(6):1478-81.
9. Reid LO et al. Biochemistry. 2016 Aug 30;55(34):4777-86.
10. Tanaka Y et al. Oxid Med Cell Longev. 2018 Nov 25;2018:9298052.
11. Murai M et al. J Dermatol Sci. 2018 Jan;89(1):19-26.
12. Brem R et al. Sci Rep. 2017 Jun 27;7(1):4310.
The melatonin precursor tryptophan, an amino acid essential in the human diet, has been shown to display antioxidant effects.1 FICZ (also known as 6-formylindolo[3,2-b]carbazole) is a photoproduct of tryptophan that is engendered by exposure to UVB.2 This column discusses the beneficial and detrimental influence of FICZ in skin health.
Antioxidant activity
In 2005, Trommer and Neubert devised a skin lipid model system to screen 47 various compounds (drugs, plant extracts, other plant constituents, and polysaccharides) for topical antioxidative activity in response to UV-induced lipid peroxidation. Among the drugs evaluated, they observed that tryptophan exerted antioxidant effects.3
Wound healing potential
A murine study by Bandeira et al. in 2015 revealed that tryptophan-induced mitigation of the inflammatory response and indoleamine 2, 3-dioxygenase expression may have enhanced skin wound healing in mice who were repeatedly stressed.4
Antifibrotic activity
In 2018, Murai et al. endeavored to clarify the role of FICZ in regulating the expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in normal human dermal fibroblasts. They found that FICZ assists in imparting UV-mediated antifibrotic effects through the AHR/MEK/ERK signal pathway in normal human dermal fibroblasts and, thus, shows promise as a therapeutic option for scleroderma.5
Cutaneous leishmaniasis
In 2019, Rodrigues et al. conducted a quantitative analysis of the relative expression of 170 genes involved in various biological processes in the skin biopsies from patients with cutaneous leishmaniasis caused by infection with either Leishmania major or L. tropica. They identified tryptophan-2,3-deoxygenase as a restriction factor for the disorder.6
Photosensitizing activity
Park et al. showed that FICZ, a tryptophan photoproduct and endogenous high-affinity aryl hydrocarbon receptor (AhR) agonist, exhibits nanomolar photodynamic activity as a UVA photosensitizer in epidermal keratinocytes and, thus, is possibly operative in human skin.7 Syed and Mukhtar add that FICZ is effective at nanomolar concentrations and that future research may elucidate its applicability against UV-induced adverse effects and inflammatory skin conditions.8
FICZ, oxidative stress, and cancer promotion
FICZ is known to display detrimental, as well as beneficial, influences in skin. The tryptophan photoproduct, comparable to UVB, ligates AhR, generates reactive oxygen species, and strongly photosensitizes for UVA. As Furue et al. note, FICZ upregulates the expression of terminal differentiation molecules (i.e., filaggrin and loricrin via AhR), and its application has been shown to suppress cutaneous inflammation in a psoriasis and dermatitis mouse model.2
In 2016, Reid et al. reported that the protein photodamage brought about by endogenous photosensitizers such as tryptophan tyrosine residues can contribute to the deleterious impact of UVA on human skin.9
In 2018, Tanaka et al. showed that FICZ imparts a cascade of events tantamount in some cases to UVB, as it promoted the synthesis of proinflammatory cytokines such as interleukin (IL)-1 alpha, IL-1 beta, and IL-6 and boosted reactive oxygen species generation in human HaCaT keratinocytes in an AhR-dependent fashion. They concluded that observing FICZ activity contributes to the understanding of how UVB damages organisms.10
That same year, Murai et al. assessed the effects of FICZ on TGF-beta-mediated ACTA2 and collagen I expression in normal human dermal fibroblasts. They determined that it may act as a key chromophore and one approach to mitigating the effects of photoaging may be to downregulate FICZ signaling.11
A year earlier, Brem et al. showed that the combined effect of FICZ and UVA engendered significant protein damage in HaCaT human keratinocytes, with the oxidation yielded from the combination of FICZ and UVA blocking the removal of potentially mutagenic UVB-induced DNA photolesions by nucleotide excision repair. The researchers concluded that the development of FICZ may raise the risk of incurring skin cancer resulting from sun exposure via the promotion of photochemical impairment of the nucleotide excision repair proteome, which in turn inhibits the removal of UVB-induced DNA lesions.12
Conclusion
However, the tryptophan photoproduct FICZ, which results from UVB exposure, presents as a complicated substance, conferring healthy and harmful effects. Much more research is necessary to determine how best to harness and direct the useful activities of tryptophan and FICZ without incurring damaging effects. Nanotechnology may be one useful avenue of investigation for this purpose.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.
References
1. Trommer H et al. J Pharm Pharmacol. 2003 Oct;55(10):1379-88.
2. Furue M et al. G Ital Dermatol Venereol. 2019 Feb;154(1):37-41.
3. Trommer H and Neubert RH. J Pharm Pharm Sci. 2005 Sep 15;8(3):494-506.
4. Bandeira LG et al. PLoS One. 2015 Jun 9:10(6):e0128439.
5. Murai M et al. J Dermatol Sci. 2018 Jul;91(1):97-103.
6. Rodrigues V et al. Front Cell Infect Microbiol. 2019 Oct 4;9:338. eCollection 2019.
7. Park SL et al. J Invest Dermatol. 2015 Jun;135(6):1649-58.
8. Syed DN and Mukhtar H. J Invest Dermatol. 2015 Jun;135(6):1478-81.
9. Reid LO et al. Biochemistry. 2016 Aug 30;55(34):4777-86.
10. Tanaka Y et al. Oxid Med Cell Longev. 2018 Nov 25;2018:9298052.
11. Murai M et al. J Dermatol Sci. 2018 Jan;89(1):19-26.
12. Brem R et al. Sci Rep. 2017 Jun 27;7(1):4310.
Vetiver: More than a pleasant aroma?
An important ingredient in the contemporary perfume and cosmetics industries, vetiver, is the only grass cultivated throughout the world to retain its essential oil, which contains sesquiterpene alcohols and hydrocarbons.1-3 Field and glasshouse studies have revealed that vetiver grass can tolerate extreme variations in climate well, including protracted drought, floods, submergence, temperature, and soils high in acidity, alkalinity, and various heavy metals. Its heartiness may explain its continuing or even increasing use in fragrances and other products pertinent to skin health as humanity strives to adapt to climate change.4 In a 2017 review of various commercial essential oils as antimicrobial therapy for cutaneous disorders, Orchard and van Vuuren identified vetiver as warranting particular attention for its capacity to confer broad benefits to the skin in addressing acne, cuts, eczema, oiliness, sores, wounds, and aging skin.5 The focus of this column will be the dermatologic potential of vetiver.
Chemical constituents
Vetiver is thought to be one of the most complex of the essential oils owing to the hundreds of sesquiterpene derivatives with large structural diversity that contribute to its composition. 3
In a 2012 analysis of the components of South Indian vetiver oils, Mallavarapu et al. found an abundance of sesquiterpenes and oxygenated sesquiterpenes with cedrane, bisabolane, eudesmane, eremophilane, and zizaane skeletons. The primary constituents identified in the four oils evaluated included eudesma-4,6-diene (delta-selinene) + beta-vetispirene (3.9%-6.1%), beta-vetivenene (0.9%-9.4%), 13-nor-trans-eudesma-4(15),7-dien-11-one + amorph-4-en-10-ol (5.0%-6.4%), trans-eudesma-4(15),7-dien-12-ol (vetiselinenol) + (E)-opposita-4(15),7(11)-dien-12-ol (3.7%-5.9%), eremophila-1 (10),11-dien-2alpha-ol (nootkatol) + ziza-6(13)-en-12-ol (khusimol) (16.1%-19.2%), and eremophila-1(10),7(11)-dien-2alpha-ol (isonootkatol) + (E)-eremophila-1(10),7(11)-12-ol (isovalencenol) (5.6%-6.9%).6
Antimicrobial activity
In 2012, Saikia et al. assessed the antimycobacterial activity of Vetiveria zizanioides against Mycobacterium tuberculosis H(37)Rv and H(37)Ra strains. Their results showed that ethanolic extracts and hexane fractions displayed robust antimycobacterial properties, buttressing the traditional medical uses of the plant, as well as consideration of this agent as a modern antituberculosis agent.7
Two years later, Dos Santos et al. showed that Vetiveria zizanioides roots grown in Brazil exhibited notable antimicrobial effects against various pathogenic organisms.8In 2017, Burger et al. showed that vetiver essential oil primarily contributes its scent to cosmetic formulations but also displayed antimicrobial activity against Gram-positive bacterial strains, as well as one strain of Candida glabrata. They suggest that vetiver should be considered for its antimicrobial capacity as an added bonus to cosmetic formulations.2
In a 2018 study to ascertain the antimicrobial activity of 247 essential oil combinations against five reference strains of wound pathogens, Orchard et al. found that 26 combinations exhibited extensive antimicrobial activity. Sandalwood and vetiver were found to contribute most to antimicrobial function when used in combination. The investigators concluded that such combinations warrant consideration for wound therapy.9
Antiacne activity
In 2018, Orchard et al. conducted another study of the efficacy of commercial essential oil combinations against the two pathogens responsible for acne, Propionibacterium acnes and Staphlyococcus epidermidis. They investigated 408 combinations, of which 167 exhibited notable antimicrobial activity. They observed that the combination with the lowest minimum inhibitory concentration value against P. acnes and S. epidermidis was vetiver and cinnamon bark.10 This usage points to the potential of vetiver use as an antiacne ingredient.
Safety
The Scientific Committee on Consumer Safety (SCCS) offered a final opinion on the safety of the fragrance ingredient acetylated vetiver oil in 2019, declaring its use with 1% alpha-tocopherol in cosmetic leave-on and rinse-off products safe at proposed concentration levels. They noted that acetylated vetiver oil has been used for several years without provoking contact allergies.11
Conclusion
Much more research is necessary to determine just what kind of a role this perfumery powerhouse can play in dermatology.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.
References
1. Del Giudice L et al. Environ Microbiol. 2008 Oct;10(10):2824-41.
2. Burger P et al. Medicines (Basel). 2017 Jun 16;4(2):41.
3. Belhassen E et al. Chem Biodivers. 2014 Nov;11(11):1821–42.
4. Danh LT et al. Int J Phytoremediation. 2009 Oct-Dec;11(8):664–91.
5. Orchard A and van Vuuren S. Evid Based Complement Alternat Med. 2017;2017:4517971.
6. Mallavarapu GR et al. Nat Prod Commun. 2012 Feb;7(2):223–5.
7. Saikia D et al. Complement Ther Med. 2012 Dec;20(6):434–6.
8. Dos Santos DS et al. Acta Pharm. 2014 Dec;64(4):495-501.
9. Orchard A et al. Chem Biodivers. 2018 Dec;15(12):e1800405.
10. Orchard A et al. Int J Cosmet Sci. 2018 Mar 24. [Epub ahead of print].
11. SCCS members & External experts. Regul Toxicol Pharmacol. 2019 Oct;107:104389.
An important ingredient in the contemporary perfume and cosmetics industries, vetiver, is the only grass cultivated throughout the world to retain its essential oil, which contains sesquiterpene alcohols and hydrocarbons.1-3 Field and glasshouse studies have revealed that vetiver grass can tolerate extreme variations in climate well, including protracted drought, floods, submergence, temperature, and soils high in acidity, alkalinity, and various heavy metals. Its heartiness may explain its continuing or even increasing use in fragrances and other products pertinent to skin health as humanity strives to adapt to climate change.4 In a 2017 review of various commercial essential oils as antimicrobial therapy for cutaneous disorders, Orchard and van Vuuren identified vetiver as warranting particular attention for its capacity to confer broad benefits to the skin in addressing acne, cuts, eczema, oiliness, sores, wounds, and aging skin.5 The focus of this column will be the dermatologic potential of vetiver.
Chemical constituents
Vetiver is thought to be one of the most complex of the essential oils owing to the hundreds of sesquiterpene derivatives with large structural diversity that contribute to its composition. 3
In a 2012 analysis of the components of South Indian vetiver oils, Mallavarapu et al. found an abundance of sesquiterpenes and oxygenated sesquiterpenes with cedrane, bisabolane, eudesmane, eremophilane, and zizaane skeletons. The primary constituents identified in the four oils evaluated included eudesma-4,6-diene (delta-selinene) + beta-vetispirene (3.9%-6.1%), beta-vetivenene (0.9%-9.4%), 13-nor-trans-eudesma-4(15),7-dien-11-one + amorph-4-en-10-ol (5.0%-6.4%), trans-eudesma-4(15),7-dien-12-ol (vetiselinenol) + (E)-opposita-4(15),7(11)-dien-12-ol (3.7%-5.9%), eremophila-1 (10),11-dien-2alpha-ol (nootkatol) + ziza-6(13)-en-12-ol (khusimol) (16.1%-19.2%), and eremophila-1(10),7(11)-dien-2alpha-ol (isonootkatol) + (E)-eremophila-1(10),7(11)-12-ol (isovalencenol) (5.6%-6.9%).6
Antimicrobial activity
In 2012, Saikia et al. assessed the antimycobacterial activity of Vetiveria zizanioides against Mycobacterium tuberculosis H(37)Rv and H(37)Ra strains. Their results showed that ethanolic extracts and hexane fractions displayed robust antimycobacterial properties, buttressing the traditional medical uses of the plant, as well as consideration of this agent as a modern antituberculosis agent.7
Two years later, Dos Santos et al. showed that Vetiveria zizanioides roots grown in Brazil exhibited notable antimicrobial effects against various pathogenic organisms.8In 2017, Burger et al. showed that vetiver essential oil primarily contributes its scent to cosmetic formulations but also displayed antimicrobial activity against Gram-positive bacterial strains, as well as one strain of Candida glabrata. They suggest that vetiver should be considered for its antimicrobial capacity as an added bonus to cosmetic formulations.2
In a 2018 study to ascertain the antimicrobial activity of 247 essential oil combinations against five reference strains of wound pathogens, Orchard et al. found that 26 combinations exhibited extensive antimicrobial activity. Sandalwood and vetiver were found to contribute most to antimicrobial function when used in combination. The investigators concluded that such combinations warrant consideration for wound therapy.9
Antiacne activity
In 2018, Orchard et al. conducted another study of the efficacy of commercial essential oil combinations against the two pathogens responsible for acne, Propionibacterium acnes and Staphlyococcus epidermidis. They investigated 408 combinations, of which 167 exhibited notable antimicrobial activity. They observed that the combination with the lowest minimum inhibitory concentration value against P. acnes and S. epidermidis was vetiver and cinnamon bark.10 This usage points to the potential of vetiver use as an antiacne ingredient.
Safety
The Scientific Committee on Consumer Safety (SCCS) offered a final opinion on the safety of the fragrance ingredient acetylated vetiver oil in 2019, declaring its use with 1% alpha-tocopherol in cosmetic leave-on and rinse-off products safe at proposed concentration levels. They noted that acetylated vetiver oil has been used for several years without provoking contact allergies.11
Conclusion
Much more research is necessary to determine just what kind of a role this perfumery powerhouse can play in dermatology.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.
References
1. Del Giudice L et al. Environ Microbiol. 2008 Oct;10(10):2824-41.
2. Burger P et al. Medicines (Basel). 2017 Jun 16;4(2):41.
3. Belhassen E et al. Chem Biodivers. 2014 Nov;11(11):1821–42.
4. Danh LT et al. Int J Phytoremediation. 2009 Oct-Dec;11(8):664–91.
5. Orchard A and van Vuuren S. Evid Based Complement Alternat Med. 2017;2017:4517971.
6. Mallavarapu GR et al. Nat Prod Commun. 2012 Feb;7(2):223–5.
7. Saikia D et al. Complement Ther Med. 2012 Dec;20(6):434–6.
8. Dos Santos DS et al. Acta Pharm. 2014 Dec;64(4):495-501.
9. Orchard A et al. Chem Biodivers. 2018 Dec;15(12):e1800405.
10. Orchard A et al. Int J Cosmet Sci. 2018 Mar 24. [Epub ahead of print].
11. SCCS members & External experts. Regul Toxicol Pharmacol. 2019 Oct;107:104389.
An important ingredient in the contemporary perfume and cosmetics industries, vetiver, is the only grass cultivated throughout the world to retain its essential oil, which contains sesquiterpene alcohols and hydrocarbons.1-3 Field and glasshouse studies have revealed that vetiver grass can tolerate extreme variations in climate well, including protracted drought, floods, submergence, temperature, and soils high in acidity, alkalinity, and various heavy metals. Its heartiness may explain its continuing or even increasing use in fragrances and other products pertinent to skin health as humanity strives to adapt to climate change.4 In a 2017 review of various commercial essential oils as antimicrobial therapy for cutaneous disorders, Orchard and van Vuuren identified vetiver as warranting particular attention for its capacity to confer broad benefits to the skin in addressing acne, cuts, eczema, oiliness, sores, wounds, and aging skin.5 The focus of this column will be the dermatologic potential of vetiver.
Chemical constituents
Vetiver is thought to be one of the most complex of the essential oils owing to the hundreds of sesquiterpene derivatives with large structural diversity that contribute to its composition. 3
In a 2012 analysis of the components of South Indian vetiver oils, Mallavarapu et al. found an abundance of sesquiterpenes and oxygenated sesquiterpenes with cedrane, bisabolane, eudesmane, eremophilane, and zizaane skeletons. The primary constituents identified in the four oils evaluated included eudesma-4,6-diene (delta-selinene) + beta-vetispirene (3.9%-6.1%), beta-vetivenene (0.9%-9.4%), 13-nor-trans-eudesma-4(15),7-dien-11-one + amorph-4-en-10-ol (5.0%-6.4%), trans-eudesma-4(15),7-dien-12-ol (vetiselinenol) + (E)-opposita-4(15),7(11)-dien-12-ol (3.7%-5.9%), eremophila-1 (10),11-dien-2alpha-ol (nootkatol) + ziza-6(13)-en-12-ol (khusimol) (16.1%-19.2%), and eremophila-1(10),7(11)-dien-2alpha-ol (isonootkatol) + (E)-eremophila-1(10),7(11)-12-ol (isovalencenol) (5.6%-6.9%).6
Antimicrobial activity
In 2012, Saikia et al. assessed the antimycobacterial activity of Vetiveria zizanioides against Mycobacterium tuberculosis H(37)Rv and H(37)Ra strains. Their results showed that ethanolic extracts and hexane fractions displayed robust antimycobacterial properties, buttressing the traditional medical uses of the plant, as well as consideration of this agent as a modern antituberculosis agent.7
Two years later, Dos Santos et al. showed that Vetiveria zizanioides roots grown in Brazil exhibited notable antimicrobial effects against various pathogenic organisms.8In 2017, Burger et al. showed that vetiver essential oil primarily contributes its scent to cosmetic formulations but also displayed antimicrobial activity against Gram-positive bacterial strains, as well as one strain of Candida glabrata. They suggest that vetiver should be considered for its antimicrobial capacity as an added bonus to cosmetic formulations.2
In a 2018 study to ascertain the antimicrobial activity of 247 essential oil combinations against five reference strains of wound pathogens, Orchard et al. found that 26 combinations exhibited extensive antimicrobial activity. Sandalwood and vetiver were found to contribute most to antimicrobial function when used in combination. The investigators concluded that such combinations warrant consideration for wound therapy.9
Antiacne activity
In 2018, Orchard et al. conducted another study of the efficacy of commercial essential oil combinations against the two pathogens responsible for acne, Propionibacterium acnes and Staphlyococcus epidermidis. They investigated 408 combinations, of which 167 exhibited notable antimicrobial activity. They observed that the combination with the lowest minimum inhibitory concentration value against P. acnes and S. epidermidis was vetiver and cinnamon bark.10 This usage points to the potential of vetiver use as an antiacne ingredient.
Safety
The Scientific Committee on Consumer Safety (SCCS) offered a final opinion on the safety of the fragrance ingredient acetylated vetiver oil in 2019, declaring its use with 1% alpha-tocopherol in cosmetic leave-on and rinse-off products safe at proposed concentration levels. They noted that acetylated vetiver oil has been used for several years without provoking contact allergies.11
Conclusion
Much more research is necessary to determine just what kind of a role this perfumery powerhouse can play in dermatology.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.
References
1. Del Giudice L et al. Environ Microbiol. 2008 Oct;10(10):2824-41.
2. Burger P et al. Medicines (Basel). 2017 Jun 16;4(2):41.
3. Belhassen E et al. Chem Biodivers. 2014 Nov;11(11):1821–42.
4. Danh LT et al. Int J Phytoremediation. 2009 Oct-Dec;11(8):664–91.
5. Orchard A and van Vuuren S. Evid Based Complement Alternat Med. 2017;2017:4517971.
6. Mallavarapu GR et al. Nat Prod Commun. 2012 Feb;7(2):223–5.
7. Saikia D et al. Complement Ther Med. 2012 Dec;20(6):434–6.
8. Dos Santos DS et al. Acta Pharm. 2014 Dec;64(4):495-501.
9. Orchard A et al. Chem Biodivers. 2018 Dec;15(12):e1800405.
10. Orchard A et al. Int J Cosmet Sci. 2018 Mar 24. [Epub ahead of print].
11. SCCS members & External experts. Regul Toxicol Pharmacol. 2019 Oct;107:104389.
Exsanguinating the truth about dragon’s blood in cosmeceuticals
The use of dragon’s blood is renowned among various medical traditions around the world.1,2 It is known to confer anti-inflammatory, antioxidant, antitumor, antimicrobial, and wound healing benefits, among others. Dragon’s blood and its characteristic red sap has also been used in folk magic and as a coloring substance and varnish.1 In addition, dragon’s blood resin is one of the many botanical agents with roots in traditional medicine that are among the bioactive ingredients used in the booming contemporary Korean cosmeceutical agent market.3.
Many plants, only some have dermatologic properties
Essentially, the moniker “dragon’s blood” describes the deep red resin or sap that has been derived from multiple plant sources – primarily from the genera Daemonorops, Dracaena, Croton, and Pterocarpus – over multiple centuries.2,4 In traditional Chinese medicine (TCM), various plants have been used as dragon’s blood, including Butea monosperma, Liquidambar formosana, Daemonorops draco, and, more commonly now, Dracaena cochinchinensis.5
Chemical constituents and activity
Dragon’s blood represents the red exudate culled from 27 species of plants from four families. Among the six Dracaena plants (D. cochinchinensis, D. cambodiana, D. cinnabari, D. draco, D. loureiroi, and D. schizantha) from which dragon’s blood is derived, flavonoids and their oligomers are considered the main active constituents. Analgesic, anti-inflammatory, antibacterial, hypolipidemic, hypoglycemic, and cytotoxic activities have been associated with these botanicals.6
D. cochinchinensis is one source of the ethnomedicine “dragon’s blood” that has long been used in TCM. Contemporary studies have shown that the resin of D. cochinchinensis – key constituents of which include loureirin A, loureirin B, loureirin C, cochinchinenin, socotrin-4’-ol, 4’,7-dihydroxyflavan, 4-methylcholest-7-ene-3-ol, ethylparaben, resveratrol, and hydroxyphenol – exhibits antibacterial, anti-inflammatory, analgesic, antidiabetic, and antitumor activities. It has also been shown to support skin repair.4
In 2017, Wang et al. reported that flavonoids from artificially induced dragon’s blood of D. cambodiana showed antibacterial properties.7 The next year, Al Fatimi reported that the dragon’s blood derived from D. cinnabari is a key plant on Yemen’s Socotra Island, where it is used for its antifungal and antioxidant properties to treat various dermal, dental, eye, and gastrointestinal diseases in humans.8Croton lechleri (also one of the plants known as dragon’s blood), a medicinal plant found in the Amazon rainforest and characterized by its red sap, has been shown in preclinical studies to display anti-inflammatory, antioxidant, antimicrobial, antifungal, and antineoplastic activity. Pona et al. note that, while clinical studies of C. lechleri suggest wound healing and antiviral effects, the current use of this plant has limited cutaneous applications.9
Wound healing activity
In 1995, Pieters et al. performed an in vivo study on rats to assess the wound healing activity of dragon’s blood (Croton spp.) from South America. In comparing the effects with those of synthetic proanthocyanidins, the researchers verified the beneficial impact of dragon’s blood in stimulating wound contraction, crust formation, new collagen development, and epithelial layer regeneration. The dragon’s blood component 3’,4-O-dimethylcedrusin was also found to enhance healing by promoting fibroblast and collagen formation, though it was not as effective as crude dragon’s blood. The authors ascribed this effect to the proanthocyanidins in the plant.10
Late in 2003, Jones published a literature review on the evidence related to Croton lechleri (known in South America as “sangre de drago” or dragon’s blood) in support of various biological effects, particularly anti-inflammatory and wound healing capability. The results from multiple in vitro and in vivo investigations buttressed previous ethnomedical justifications for the use of dragon’s blood to treat herpes, insect bites, stomach ulcers, tumors, wounds, and diarrhea, as well as other conditions. Jones added that the sap of the plant has exhibited low toxicity and has been well tolerated in clinical studies.11
In 2012, Hu et al. investigated the impact of dragon’s blood powder with varying grain size on the transdermal absorption and adhesion of ZJHX paste, finding that, with decreasing grain size, penetration of dracorhodin increased, thus promoting transdermal permeability and adhesion.12
Lieu et al. assessed the wound healing potential of Resina Draconis, derived from D. cochinchinensis, which has long been used in traditional medicines by various cultures. In this 2013 evaluation, the investigators substantiated the traditional uses of this herb for wound healing, using excision and incision models in rats. Animals treated with D. cochinchinensis resin displayed significantly superior wound contraction and tensile strength as compared with controls, with histopathological results revealing better microvessel density and growth factor expression levels.13
In 2017, Jiang et al. showed that dracorhodin percolate, derived from dragon’s blood and used extensively to treat wound healing in TCM, accelerated wound healing in Wistar rats.14 A year later, they found that the use of dracorhodin perchlorate was effective in regulating fibroblast proliferation in vitro and in vivo to promote wound healing in rats. In addition, they noted that phosphorylated–extracellular signal-regulated kinase (ERK) in the wound tissue significantly increased with treatment of dracorhodin perchlorate ointment. The researchers called for clinical trials testing this compound in humans as the next step.15
In 2015, Namjoyan et al. conducted a randomized, double-blind, placebo-controlled clinical trial in 60 patients (between 14 and 65 years old) to assess the wound healing effect of a dragon’s blood cream on skin tag removal. Patients were visited every third day during this 3-week study, after which a significant difference in mean wound healing duration was identified. The investigators attributed the accelerated wound healing action to the phenolic constituents and alkaloid taspine in the resin. They also concluded that dragon’s blood warrants inclusion in the wound healing arsenal, while calling for studies in larger populations.16
Conclusion
The red resin extracts of multiple species of plants have and continue to be identified as “dragon’s blood.” This exudate has been used for various medical indications in traditional medicine for several centuries. Despite this lengthy history, modern research is hardly robust. Nevertheless, there are many credible reports of significant salutary activities associated with these resins and some evidence of cutaneous benefits. Much more research is necessary to determine how useful these ingredients are, despite their present use in a number of marketed cosmeceutical agents.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.
References
1. Gupta D et al. J Ethnopharmacol. 2008 Feb 12;115(3):361-80.
2. Jura-Morawiec J & Tulik. Chemoecology. 2016;26:101-5.
3. Nguyen JK et al. J Cosmet Dermatol. 2020 Jul;19(7):155-69.
4. Fan JY et al. Molecules. 2014 Jul 22;19(7):10650-69.
5. Zhang W et al. Zhongguo Zhong Yao Za Zhi. 2016 Apr;41(7):1354-7.
6. Sun J et al. J Ethnopharmacol. 2019 Nov 15;244:112138.
7. Wang H et al. Fitoterapia. 2017 Sep;121:1-5.
8. Al-Fatimi M. Plants (Basel). 2018 Oct 26;7(4):91.
9. Pona A et al. Dermatol Ther. 2019 Mar;32(2):e12786.10. Pieters L et al. Phytomedicine. 1995 Jul;2(1):17-22.
11. Jones K. J Altern Complement Med. 2003 Dec;9(6):877-96.
12. Hu Q et al. Zhongguo Zhong Yao Za Zhi. 2012 Dec;37(23):3549-53.
13. Liu H et al. Evid Based Complement Alternat Med. 2013;2013:709865.
14. Jiang XW et al. Evid Based Complement Alternat Med. 2017:8950516.
15. Jiang X et al. J Pharmacol Sci. 2018 Feb;136(2):66-72.
16. Namjoyan F et al. J Tradit Complement Med. 2015 Jan 22;6(1):37-40.
The use of dragon’s blood is renowned among various medical traditions around the world.1,2 It is known to confer anti-inflammatory, antioxidant, antitumor, antimicrobial, and wound healing benefits, among others. Dragon’s blood and its characteristic red sap has also been used in folk magic and as a coloring substance and varnish.1 In addition, dragon’s blood resin is one of the many botanical agents with roots in traditional medicine that are among the bioactive ingredients used in the booming contemporary Korean cosmeceutical agent market.3.
Many plants, only some have dermatologic properties
Essentially, the moniker “dragon’s blood” describes the deep red resin or sap that has been derived from multiple plant sources – primarily from the genera Daemonorops, Dracaena, Croton, and Pterocarpus – over multiple centuries.2,4 In traditional Chinese medicine (TCM), various plants have been used as dragon’s blood, including Butea monosperma, Liquidambar formosana, Daemonorops draco, and, more commonly now, Dracaena cochinchinensis.5
Chemical constituents and activity
Dragon’s blood represents the red exudate culled from 27 species of plants from four families. Among the six Dracaena plants (D. cochinchinensis, D. cambodiana, D. cinnabari, D. draco, D. loureiroi, and D. schizantha) from which dragon’s blood is derived, flavonoids and their oligomers are considered the main active constituents. Analgesic, anti-inflammatory, antibacterial, hypolipidemic, hypoglycemic, and cytotoxic activities have been associated with these botanicals.6
D. cochinchinensis is one source of the ethnomedicine “dragon’s blood” that has long been used in TCM. Contemporary studies have shown that the resin of D. cochinchinensis – key constituents of which include loureirin A, loureirin B, loureirin C, cochinchinenin, socotrin-4’-ol, 4’,7-dihydroxyflavan, 4-methylcholest-7-ene-3-ol, ethylparaben, resveratrol, and hydroxyphenol – exhibits antibacterial, anti-inflammatory, analgesic, antidiabetic, and antitumor activities. It has also been shown to support skin repair.4
In 2017, Wang et al. reported that flavonoids from artificially induced dragon’s blood of D. cambodiana showed antibacterial properties.7 The next year, Al Fatimi reported that the dragon’s blood derived from D. cinnabari is a key plant on Yemen’s Socotra Island, where it is used for its antifungal and antioxidant properties to treat various dermal, dental, eye, and gastrointestinal diseases in humans.8Croton lechleri (also one of the plants known as dragon’s blood), a medicinal plant found in the Amazon rainforest and characterized by its red sap, has been shown in preclinical studies to display anti-inflammatory, antioxidant, antimicrobial, antifungal, and antineoplastic activity. Pona et al. note that, while clinical studies of C. lechleri suggest wound healing and antiviral effects, the current use of this plant has limited cutaneous applications.9
Wound healing activity
In 1995, Pieters et al. performed an in vivo study on rats to assess the wound healing activity of dragon’s blood (Croton spp.) from South America. In comparing the effects with those of synthetic proanthocyanidins, the researchers verified the beneficial impact of dragon’s blood in stimulating wound contraction, crust formation, new collagen development, and epithelial layer regeneration. The dragon’s blood component 3’,4-O-dimethylcedrusin was also found to enhance healing by promoting fibroblast and collagen formation, though it was not as effective as crude dragon’s blood. The authors ascribed this effect to the proanthocyanidins in the plant.10
Late in 2003, Jones published a literature review on the evidence related to Croton lechleri (known in South America as “sangre de drago” or dragon’s blood) in support of various biological effects, particularly anti-inflammatory and wound healing capability. The results from multiple in vitro and in vivo investigations buttressed previous ethnomedical justifications for the use of dragon’s blood to treat herpes, insect bites, stomach ulcers, tumors, wounds, and diarrhea, as well as other conditions. Jones added that the sap of the plant has exhibited low toxicity and has been well tolerated in clinical studies.11
In 2012, Hu et al. investigated the impact of dragon’s blood powder with varying grain size on the transdermal absorption and adhesion of ZJHX paste, finding that, with decreasing grain size, penetration of dracorhodin increased, thus promoting transdermal permeability and adhesion.12
Lieu et al. assessed the wound healing potential of Resina Draconis, derived from D. cochinchinensis, which has long been used in traditional medicines by various cultures. In this 2013 evaluation, the investigators substantiated the traditional uses of this herb for wound healing, using excision and incision models in rats. Animals treated with D. cochinchinensis resin displayed significantly superior wound contraction and tensile strength as compared with controls, with histopathological results revealing better microvessel density and growth factor expression levels.13
In 2017, Jiang et al. showed that dracorhodin percolate, derived from dragon’s blood and used extensively to treat wound healing in TCM, accelerated wound healing in Wistar rats.14 A year later, they found that the use of dracorhodin perchlorate was effective in regulating fibroblast proliferation in vitro and in vivo to promote wound healing in rats. In addition, they noted that phosphorylated–extracellular signal-regulated kinase (ERK) in the wound tissue significantly increased with treatment of dracorhodin perchlorate ointment. The researchers called for clinical trials testing this compound in humans as the next step.15
In 2015, Namjoyan et al. conducted a randomized, double-blind, placebo-controlled clinical trial in 60 patients (between 14 and 65 years old) to assess the wound healing effect of a dragon’s blood cream on skin tag removal. Patients were visited every third day during this 3-week study, after which a significant difference in mean wound healing duration was identified. The investigators attributed the accelerated wound healing action to the phenolic constituents and alkaloid taspine in the resin. They also concluded that dragon’s blood warrants inclusion in the wound healing arsenal, while calling for studies in larger populations.16
Conclusion
The red resin extracts of multiple species of plants have and continue to be identified as “dragon’s blood.” This exudate has been used for various medical indications in traditional medicine for several centuries. Despite this lengthy history, modern research is hardly robust. Nevertheless, there are many credible reports of significant salutary activities associated with these resins and some evidence of cutaneous benefits. Much more research is necessary to determine how useful these ingredients are, despite their present use in a number of marketed cosmeceutical agents.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.
References
1. Gupta D et al. J Ethnopharmacol. 2008 Feb 12;115(3):361-80.
2. Jura-Morawiec J & Tulik. Chemoecology. 2016;26:101-5.
3. Nguyen JK et al. J Cosmet Dermatol. 2020 Jul;19(7):155-69.
4. Fan JY et al. Molecules. 2014 Jul 22;19(7):10650-69.
5. Zhang W et al. Zhongguo Zhong Yao Za Zhi. 2016 Apr;41(7):1354-7.
6. Sun J et al. J Ethnopharmacol. 2019 Nov 15;244:112138.
7. Wang H et al. Fitoterapia. 2017 Sep;121:1-5.
8. Al-Fatimi M. Plants (Basel). 2018 Oct 26;7(4):91.
9. Pona A et al. Dermatol Ther. 2019 Mar;32(2):e12786.10. Pieters L et al. Phytomedicine. 1995 Jul;2(1):17-22.
11. Jones K. J Altern Complement Med. 2003 Dec;9(6):877-96.
12. Hu Q et al. Zhongguo Zhong Yao Za Zhi. 2012 Dec;37(23):3549-53.
13. Liu H et al. Evid Based Complement Alternat Med. 2013;2013:709865.
14. Jiang XW et al. Evid Based Complement Alternat Med. 2017:8950516.
15. Jiang X et al. J Pharmacol Sci. 2018 Feb;136(2):66-72.
16. Namjoyan F et al. J Tradit Complement Med. 2015 Jan 22;6(1):37-40.
The use of dragon’s blood is renowned among various medical traditions around the world.1,2 It is known to confer anti-inflammatory, antioxidant, antitumor, antimicrobial, and wound healing benefits, among others. Dragon’s blood and its characteristic red sap has also been used in folk magic and as a coloring substance and varnish.1 In addition, dragon’s blood resin is one of the many botanical agents with roots in traditional medicine that are among the bioactive ingredients used in the booming contemporary Korean cosmeceutical agent market.3.
Many plants, only some have dermatologic properties
Essentially, the moniker “dragon’s blood” describes the deep red resin or sap that has been derived from multiple plant sources – primarily from the genera Daemonorops, Dracaena, Croton, and Pterocarpus – over multiple centuries.2,4 In traditional Chinese medicine (TCM), various plants have been used as dragon’s blood, including Butea monosperma, Liquidambar formosana, Daemonorops draco, and, more commonly now, Dracaena cochinchinensis.5
Chemical constituents and activity
Dragon’s blood represents the red exudate culled from 27 species of plants from four families. Among the six Dracaena plants (D. cochinchinensis, D. cambodiana, D. cinnabari, D. draco, D. loureiroi, and D. schizantha) from which dragon’s blood is derived, flavonoids and their oligomers are considered the main active constituents. Analgesic, anti-inflammatory, antibacterial, hypolipidemic, hypoglycemic, and cytotoxic activities have been associated with these botanicals.6
D. cochinchinensis is one source of the ethnomedicine “dragon’s blood” that has long been used in TCM. Contemporary studies have shown that the resin of D. cochinchinensis – key constituents of which include loureirin A, loureirin B, loureirin C, cochinchinenin, socotrin-4’-ol, 4’,7-dihydroxyflavan, 4-methylcholest-7-ene-3-ol, ethylparaben, resveratrol, and hydroxyphenol – exhibits antibacterial, anti-inflammatory, analgesic, antidiabetic, and antitumor activities. It has also been shown to support skin repair.4
In 2017, Wang et al. reported that flavonoids from artificially induced dragon’s blood of D. cambodiana showed antibacterial properties.7 The next year, Al Fatimi reported that the dragon’s blood derived from D. cinnabari is a key plant on Yemen’s Socotra Island, where it is used for its antifungal and antioxidant properties to treat various dermal, dental, eye, and gastrointestinal diseases in humans.8Croton lechleri (also one of the plants known as dragon’s blood), a medicinal plant found in the Amazon rainforest and characterized by its red sap, has been shown in preclinical studies to display anti-inflammatory, antioxidant, antimicrobial, antifungal, and antineoplastic activity. Pona et al. note that, while clinical studies of C. lechleri suggest wound healing and antiviral effects, the current use of this plant has limited cutaneous applications.9
Wound healing activity
In 1995, Pieters et al. performed an in vivo study on rats to assess the wound healing activity of dragon’s blood (Croton spp.) from South America. In comparing the effects with those of synthetic proanthocyanidins, the researchers verified the beneficial impact of dragon’s blood in stimulating wound contraction, crust formation, new collagen development, and epithelial layer regeneration. The dragon’s blood component 3’,4-O-dimethylcedrusin was also found to enhance healing by promoting fibroblast and collagen formation, though it was not as effective as crude dragon’s blood. The authors ascribed this effect to the proanthocyanidins in the plant.10
Late in 2003, Jones published a literature review on the evidence related to Croton lechleri (known in South America as “sangre de drago” or dragon’s blood) in support of various biological effects, particularly anti-inflammatory and wound healing capability. The results from multiple in vitro and in vivo investigations buttressed previous ethnomedical justifications for the use of dragon’s blood to treat herpes, insect bites, stomach ulcers, tumors, wounds, and diarrhea, as well as other conditions. Jones added that the sap of the plant has exhibited low toxicity and has been well tolerated in clinical studies.11
In 2012, Hu et al. investigated the impact of dragon’s blood powder with varying grain size on the transdermal absorption and adhesion of ZJHX paste, finding that, with decreasing grain size, penetration of dracorhodin increased, thus promoting transdermal permeability and adhesion.12
Lieu et al. assessed the wound healing potential of Resina Draconis, derived from D. cochinchinensis, which has long been used in traditional medicines by various cultures. In this 2013 evaluation, the investigators substantiated the traditional uses of this herb for wound healing, using excision and incision models in rats. Animals treated with D. cochinchinensis resin displayed significantly superior wound contraction and tensile strength as compared with controls, with histopathological results revealing better microvessel density and growth factor expression levels.13
In 2017, Jiang et al. showed that dracorhodin percolate, derived from dragon’s blood and used extensively to treat wound healing in TCM, accelerated wound healing in Wistar rats.14 A year later, they found that the use of dracorhodin perchlorate was effective in regulating fibroblast proliferation in vitro and in vivo to promote wound healing in rats. In addition, they noted that phosphorylated–extracellular signal-regulated kinase (ERK) in the wound tissue significantly increased with treatment of dracorhodin perchlorate ointment. The researchers called for clinical trials testing this compound in humans as the next step.15
In 2015, Namjoyan et al. conducted a randomized, double-blind, placebo-controlled clinical trial in 60 patients (between 14 and 65 years old) to assess the wound healing effect of a dragon’s blood cream on skin tag removal. Patients were visited every third day during this 3-week study, after which a significant difference in mean wound healing duration was identified. The investigators attributed the accelerated wound healing action to the phenolic constituents and alkaloid taspine in the resin. They also concluded that dragon’s blood warrants inclusion in the wound healing arsenal, while calling for studies in larger populations.16
Conclusion
The red resin extracts of multiple species of plants have and continue to be identified as “dragon’s blood.” This exudate has been used for various medical indications in traditional medicine for several centuries. Despite this lengthy history, modern research is hardly robust. Nevertheless, there are many credible reports of significant salutary activities associated with these resins and some evidence of cutaneous benefits. Much more research is necessary to determine how useful these ingredients are, despite their present use in a number of marketed cosmeceutical agents.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.
References
1. Gupta D et al. J Ethnopharmacol. 2008 Feb 12;115(3):361-80.
2. Jura-Morawiec J & Tulik. Chemoecology. 2016;26:101-5.
3. Nguyen JK et al. J Cosmet Dermatol. 2020 Jul;19(7):155-69.
4. Fan JY et al. Molecules. 2014 Jul 22;19(7):10650-69.
5. Zhang W et al. Zhongguo Zhong Yao Za Zhi. 2016 Apr;41(7):1354-7.
6. Sun J et al. J Ethnopharmacol. 2019 Nov 15;244:112138.
7. Wang H et al. Fitoterapia. 2017 Sep;121:1-5.
8. Al-Fatimi M. Plants (Basel). 2018 Oct 26;7(4):91.
9. Pona A et al. Dermatol Ther. 2019 Mar;32(2):e12786.10. Pieters L et al. Phytomedicine. 1995 Jul;2(1):17-22.
11. Jones K. J Altern Complement Med. 2003 Dec;9(6):877-96.
12. Hu Q et al. Zhongguo Zhong Yao Za Zhi. 2012 Dec;37(23):3549-53.
13. Liu H et al. Evid Based Complement Alternat Med. 2013;2013:709865.
14. Jiang XW et al. Evid Based Complement Alternat Med. 2017:8950516.
15. Jiang X et al. J Pharmacol Sci. 2018 Feb;136(2):66-72.
16. Namjoyan F et al. J Tradit Complement Med. 2015 Jan 22;6(1):37-40.