Leslie S. Baumann, MD

As clinicians who have been in practice for even a relatively short period of time know, patient compliance is an integral aspect of achieving optimal patient outcomes. However, studies show that patient compliance with treatment of many dermatologic disorders, including acne and psoriasis, is often poor.^1,2

In 2007, Feldman showed that patients are more likely to use their products in the days before and the days after their dermatologist visit.³ He suggested that more frequent office visits would boost compliance. I have found that this is true and I recommend seeing patients every 4 weeks when implementing a new treatment regimen. I have also found that combining prescription medications with the proper corresponding skin care products helps decrease side effects and speed results when patients apply the products correctly.

To achieve good patient outcomes, the patient needs to:

• Understand what medications and products to use.
• Understand when and how to use the products.
• Understand the order in which to use the products (step 1, step 2, etc.).
• Purchase the products (from you or elsewhere).
• Tell you if they do not purchase the products, for whatever reason (insurance will not cover, too expensive, could not find them, etc.).
• Use the products consistently.
• Inform you if they do not use the products (too busy, did not have them on a trip, etc.).
• Report any side effects so you can adjust the therapy accordingly.

You can see why it is so difficult to get patients to be compliant. Many factors – such as time, memory, education level, understanding, motivation, cost, convenience, and insurance coverage – can get in the way of these important components. Giving patients a printed regimen with instructions, selling the products in your practice, and providing some sort of interaction to keep patients engaged is key. In my June 2015 Dermatology News column, I discussed why you should consider selling products in your practice. In the future, I will discuss ways to engage your patients, but for now, let’s focus on how to quickly and effectively provide your patients with printed regimens and patient instructions without increasing office visit times.
 

Streamlining the Process of Generating a Skin Care Regimen That Includes Prescription Medications

Identify patients’ phenotypes

Divide patients into phenotypes based on skin care needs to save yourself time with the recommendation process.

Many doctors do this with a disease-based approach, such as acne, rosacea, eczema, psoriasis, etc. I prefer to classify my patients according to 16 Baumann Skin Types based on four parameters: hydration status, propensity for inflammation; presence or absence of uneven pigmentation; and presence of lifestyle habits, such as sun exposure, that increase an individual’s risk of skin aging.^4,5,6 To quickly diagnose the patient as a particular Baumann Skin Type, I use a tablet-based validated questionnaire called the Baumann Skin Type Indicator (BSTI).⁷ This questionnaire is self-administered by the patient in the waiting room and serves several purposes that facilitate my practice:

• To collect historical and current data.
• To diagnose skin type.
• To ask specifically about skin allergies.
• To learn preferences such as tinted vs. nontinted, or chemical vs. physical sunscreen.
• To inquire about what issues the patient wants to discuss, such as thinning eyelashes, hair loss, dry body skin, toenail fungus, warts, eczema, and other topics that might not come up during the appointment.
• To learn and document habits that affect the skin, such as tanning bed exposure, sun exposure, and smoking.
• To stimulate the patient to think about how daily actions such as sunscreen use and sun exposure affect their skin health.

Whether you choose to use my questionnaire or one of your own, using a validated method that can be initiated by staff in the waiting room saves time in the exam room.
 

Include prescription medications in the skin care regimen

Often, we think of skin care regimens and prescription medications as two different entities. In actuality, these should be combined.

For example, when treating acne, every item the patient uses plays a role. For example, if they are washing the face with Ivory soap and then applying benzoyl peroxide and a retinoid they will experience dryness and irritation. Then they will buy a moisturizer that might cause acne. (It is very hard for them to know which moisturizers and sunscreens will not worsen acne). By providing them with the exact names of cleansers, moisturizers, and sunscreens to use, they will be better able to tolerate their prescription acne medications.

The same is true with psoriasis, eczema, seborrheic dermatitis, contact dermatitis, and most of the other ailments that dermatologists treat. You must also tell them the order to use them in. For example, I always have patients apply the retinoid over the noncomedogenic moisturizer for the first few weeks to help them adjust to the retinoid. Later, once they have passed the high-risk period of retinoid dermatitis, I move the retinoid to under the moisturizer.

Psoriasis treatment (topical) is another good example. If they are going to use a surfactant-laden soap on their skin, they will impair their barrier and absorb more of the topically applied drug. Conversely, if they use a barrier repair moisturizer, they will absorb less. Telling the patients exactly which body cleansers and moisturizers to use with topical psoriasis medications will help standardize the response. For this reason, giving patients printed regimens is not limited to treatment of acne, rosacea, and photoaging, but rather should be done for patients with all skin issues and phenotypes.

Have informational material for each phenotype at your fingertips

You can have a plan for each patient phenotype that is designed ahead of time. You will save yourself hours of time if you have preprinted instructions sheets made for each of these phenotypes. You can use Touch MD, The Canfield Visia Camera Patient Portal, your EMR, or other systems to organize this material and deliver it to patients.

I personally use the Skin Type Solutions Software System (STSFranchise.com) that I developed and patented to house and export my patient instructions. Using a standardized methodology to provide educational information through video, preprinted sheets, emails, and other methods allows you to educate your patients at their pace and in the media with which they are most comfortable. To have this flexibility, the educational information must be developed prior to the patient visit. Categorizing the education information by phenotype makes this possible.

What the informational material should contain

Educational information should include important information about the phenotype, the do’s and don’ts for the phenotype, an exact skin care regimen containing clear steps that include product names including brand names, prescription medications, the order in which the products should be applied, and clear instructions on how to use the products.

The patient should be informed about what to do if anticipated adverse events occur, such as redness and peeling from retinoids or dryness from benzoyl peroxide. The same is true about injectable biologic medications for psoriasis. The patients need information on where to inject the product, how often, how to clean the skin beforehand, and what to put on the skin after the injections. It is always important with any skin issue for the patient to know when to contact the office. The American Academy of Dermatology and other organizations offer educational brochures for patients, but they cannot be customized. Patients prefer a customized approach to educational material. They don’t want to read information that does not apply to them. I have found that dividing patients into 16 distinct Baumann Skin Types helps target the right information to the corresponding skin phenotypes.

Summary

Patients need education and guidance to be compliant and improve their outcomes. Your staff needs to be a part of the education process, but taking the time to train your staff and educate your patients is always an issue. Developing a standardized methodology will help overcome these hurdles and solve this problem. The methodology should provide directed education and clear communication with written instructions delivered in the media of the patient’s choice. Doing this will yield better compliance and outcomes.

If you have any questions, suggestions or ideas of how to solve these issues, please share them with me at [email protected].

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 wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and “Cosmeceuticals and Cosmetic Ingredients,” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems LLC.

References

1. JAMA Dermatol. 2015 Jun;151(6):623-6.

2. J Am Acad Dermatol. 2004 Aug;51(2):212-6.

3. J Am Acad Dermatol. 2007 Jul;57(1):81-3.

4. Dermatol Clin. 2008 Jul;26(3):359-73.

5. Baumann L. Cosmetics and skin care in dermatology. In: Wolff K, ed. Fitzpatrick’s Dermatology in General Medicine, 7th ed. New York, NY: McGraw-Hill; 2008:2357-2364.

6. Baumann L. The Baumann skin typing system. In: Farage MA, Miller KW, Maibach HI, eds. Textbook of Aging Skin. Berling, Germany: Springer-Verlag; 2010:929-944.

7. Journal of Cosmetics, Dermatological Sciences and Applications. 2016;6(1):34-40.

As clinicians who have been in practice for even a relatively short period of time know, patient compliance is an integral aspect of achieving optimal patient outcomes. However, studies show that patient compliance with treatment of many dermatologic disorders, including acne and psoriasis, is often poor.^1,2

In 2007, Feldman showed that patients are more likely to use their products in the days before and the days after their dermatologist visit.³ He suggested that more frequent office visits would boost compliance. I have found that this is true and I recommend seeing patients every 4 weeks when implementing a new treatment regimen. I have also found that combining prescription medications with the proper corresponding skin care products helps decrease side effects and speed results when patients apply the products correctly.

To achieve good patient outcomes, the patient needs to:

• Understand what medications and products to use.
• Understand when and how to use the products.
• Understand the order in which to use the products (step 1, step 2, etc.).
• Purchase the products (from you or elsewhere).
• Tell you if they do not purchase the products, for whatever reason (insurance will not cover, too expensive, could not find them, etc.).
• Use the products consistently.
• Inform you if they do not use the products (too busy, did not have them on a trip, etc.).
• Report any side effects so you can adjust the therapy accordingly.

You can see why it is so difficult to get patients to be compliant. Many factors – such as time, memory, education level, understanding, motivation, cost, convenience, and insurance coverage – can get in the way of these important components. Giving patients a printed regimen with instructions, selling the products in your practice, and providing some sort of interaction to keep patients engaged is key. In my June 2015 Dermatology News column, I discussed why you should consider selling products in your practice. In the future, I will discuss ways to engage your patients, but for now, let’s focus on how to quickly and effectively provide your patients with printed regimens and patient instructions without increasing office visit times.
 

Streamlining the Process of Generating a Skin Care Regimen That Includes Prescription Medications

Identify patients’ phenotypes

Divide patients into phenotypes based on skin care needs to save yourself time with the recommendation process.

Many doctors do this with a disease-based approach, such as acne, rosacea, eczema, psoriasis, etc. I prefer to classify my patients according to 16 Baumann Skin Types based on four parameters: hydration status, propensity for inflammation; presence or absence of uneven pigmentation; and presence of lifestyle habits, such as sun exposure, that increase an individual’s risk of skin aging.^4,5,6 To quickly diagnose the patient as a particular Baumann Skin Type, I use a tablet-based validated questionnaire called the Baumann Skin Type Indicator (BSTI).⁷ This questionnaire is self-administered by the patient in the waiting room and serves several purposes that facilitate my practice:

• To collect historical and current data.
• To diagnose skin type.
• To ask specifically about skin allergies.
• To learn preferences such as tinted vs. nontinted, or chemical vs. physical sunscreen.
• To inquire about what issues the patient wants to discuss, such as thinning eyelashes, hair loss, dry body skin, toenail fungus, warts, eczema, and other topics that might not come up during the appointment.
• To learn and document habits that affect the skin, such as tanning bed exposure, sun exposure, and smoking.
• To stimulate the patient to think about how daily actions such as sunscreen use and sun exposure affect their skin health.

Whether you choose to use my questionnaire or one of your own, using a validated method that can be initiated by staff in the waiting room saves time in the exam room.
 

Include prescription medications in the skin care regimen

Often, we think of skin care regimens and prescription medications as two different entities. In actuality, these should be combined.

For example, when treating acne, every item the patient uses plays a role. For example, if they are washing the face with Ivory soap and then applying benzoyl peroxide and a retinoid they will experience dryness and irritation. Then they will buy a moisturizer that might cause acne. (It is very hard for them to know which moisturizers and sunscreens will not worsen acne). By providing them with the exact names of cleansers, moisturizers, and sunscreens to use, they will be better able to tolerate their prescription acne medications.

The same is true with psoriasis, eczema, seborrheic dermatitis, contact dermatitis, and most of the other ailments that dermatologists treat. You must also tell them the order to use them in. For example, I always have patients apply the retinoid over the noncomedogenic moisturizer for the first few weeks to help them adjust to the retinoid. Later, once they have passed the high-risk period of retinoid dermatitis, I move the retinoid to under the moisturizer.

Psoriasis treatment (topical) is another good example. If they are going to use a surfactant-laden soap on their skin, they will impair their barrier and absorb more of the topically applied drug. Conversely, if they use a barrier repair moisturizer, they will absorb less. Telling the patients exactly which body cleansers and moisturizers to use with topical psoriasis medications will help standardize the response. For this reason, giving patients printed regimens is not limited to treatment of acne, rosacea, and photoaging, but rather should be done for patients with all skin issues and phenotypes.

Have informational material for each phenotype at your fingertips

You can have a plan for each patient phenotype that is designed ahead of time. You will save yourself hours of time if you have preprinted instructions sheets made for each of these phenotypes. You can use Touch MD, The Canfield Visia Camera Patient Portal, your EMR, or other systems to organize this material and deliver it to patients.

I personally use the Skin Type Solutions Software System (STSFranchise.com) that I developed and patented to house and export my patient instructions. Using a standardized methodology to provide educational information through video, preprinted sheets, emails, and other methods allows you to educate your patients at their pace and in the media with which they are most comfortable. To have this flexibility, the educational information must be developed prior to the patient visit. Categorizing the education information by phenotype makes this possible.

What the informational material should contain

Educational information should include important information about the phenotype, the do’s and don’ts for the phenotype, an exact skin care regimen containing clear steps that include product names including brand names, prescription medications, the order in which the products should be applied, and clear instructions on how to use the products.

The patient should be informed about what to do if anticipated adverse events occur, such as redness and peeling from retinoids or dryness from benzoyl peroxide. The same is true about injectable biologic medications for psoriasis. The patients need information on where to inject the product, how often, how to clean the skin beforehand, and what to put on the skin after the injections. It is always important with any skin issue for the patient to know when to contact the office. The American Academy of Dermatology and other organizations offer educational brochures for patients, but they cannot be customized. Patients prefer a customized approach to educational material. They don’t want to read information that does not apply to them. I have found that dividing patients into 16 distinct Baumann Skin Types helps target the right information to the corresponding skin phenotypes.

Summary

Patients need education and guidance to be compliant and improve their outcomes. Your staff needs to be a part of the education process, but taking the time to train your staff and educate your patients is always an issue. Developing a standardized methodology will help overcome these hurdles and solve this problem. The methodology should provide directed education and clear communication with written instructions delivered in the media of the patient’s choice. Doing this will yield better compliance and outcomes.

If you have any questions, suggestions or ideas of how to solve these issues, please share them with me at [email protected].

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 wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and “Cosmeceuticals and Cosmetic Ingredients,” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems LLC.

References

1. JAMA Dermatol. 2015 Jun;151(6):623-6.

2. J Am Acad Dermatol. 2004 Aug;51(2):212-6.

3. J Am Acad Dermatol. 2007 Jul;57(1):81-3.

4. Dermatol Clin. 2008 Jul;26(3):359-73.

5. Baumann L. Cosmetics and skin care in dermatology. In: Wolff K, ed. Fitzpatrick’s Dermatology in General Medicine, 7th ed. New York, NY: McGraw-Hill; 2008:2357-2364.

6. Baumann L. The Baumann skin typing system. In: Farage MA, Miller KW, Maibach HI, eds. Textbook of Aging Skin. Berling, Germany: Springer-Verlag; 2010:929-944.

7. Journal of Cosmetics, Dermatological Sciences and Applications. 2016;6(1):34-40.

As clinicians who have been in practice for even a relatively short period of time know, patient compliance is an integral aspect of achieving optimal patient outcomes. However, studies show that patient compliance with treatment of many dermatologic disorders, including acne and psoriasis, is often poor.^1,2

In 2007, Feldman showed that patients are more likely to use their products in the days before and the days after their dermatologist visit.³ He suggested that more frequent office visits would boost compliance. I have found that this is true and I recommend seeing patients every 4 weeks when implementing a new treatment regimen. I have also found that combining prescription medications with the proper corresponding skin care products helps decrease side effects and speed results when patients apply the products correctly.

To achieve good patient outcomes, the patient needs to:

• Understand what medications and products to use.
• Understand when and how to use the products.
• Understand the order in which to use the products (step 1, step 2, etc.).
• Purchase the products (from you or elsewhere).
• Tell you if they do not purchase the products, for whatever reason (insurance will not cover, too expensive, could not find them, etc.).
• Use the products consistently.
• Inform you if they do not use the products (too busy, did not have them on a trip, etc.).
• Report any side effects so you can adjust the therapy accordingly.

You can see why it is so difficult to get patients to be compliant. Many factors – such as time, memory, education level, understanding, motivation, cost, convenience, and insurance coverage – can get in the way of these important components. Giving patients a printed regimen with instructions, selling the products in your practice, and providing some sort of interaction to keep patients engaged is key. In my June 2015 Dermatology News column, I discussed why you should consider selling products in your practice. In the future, I will discuss ways to engage your patients, but for now, let’s focus on how to quickly and effectively provide your patients with printed regimens and patient instructions without increasing office visit times.
 

Streamlining the Process of Generating a Skin Care Regimen That Includes Prescription Medications

Identify patients’ phenotypes

Divide patients into phenotypes based on skin care needs to save yourself time with the recommendation process.

Many doctors do this with a disease-based approach, such as acne, rosacea, eczema, psoriasis, etc. I prefer to classify my patients according to 16 Baumann Skin Types based on four parameters: hydration status, propensity for inflammation; presence or absence of uneven pigmentation; and presence of lifestyle habits, such as sun exposure, that increase an individual’s risk of skin aging.^4,5,6 To quickly diagnose the patient as a particular Baumann Skin Type, I use a tablet-based validated questionnaire called the Baumann Skin Type Indicator (BSTI).⁷ This questionnaire is self-administered by the patient in the waiting room and serves several purposes that facilitate my practice:

• To collect historical and current data.
• To diagnose skin type.
• To ask specifically about skin allergies.
• To learn preferences such as tinted vs. nontinted, or chemical vs. physical sunscreen.
• To inquire about what issues the patient wants to discuss, such as thinning eyelashes, hair loss, dry body skin, toenail fungus, warts, eczema, and other topics that might not come up during the appointment.
• To learn and document habits that affect the skin, such as tanning bed exposure, sun exposure, and smoking.
• To stimulate the patient to think about how daily actions such as sunscreen use and sun exposure affect their skin health.

Whether you choose to use my questionnaire or one of your own, using a validated method that can be initiated by staff in the waiting room saves time in the exam room.
 

Include prescription medications in the skin care regimen

Often, we think of skin care regimens and prescription medications as two different entities. In actuality, these should be combined.

For example, when treating acne, every item the patient uses plays a role. For example, if they are washing the face with Ivory soap and then applying benzoyl peroxide and a retinoid they will experience dryness and irritation. Then they will buy a moisturizer that might cause acne. (It is very hard for them to know which moisturizers and sunscreens will not worsen acne). By providing them with the exact names of cleansers, moisturizers, and sunscreens to use, they will be better able to tolerate their prescription acne medications.

The same is true with psoriasis, eczema, seborrheic dermatitis, contact dermatitis, and most of the other ailments that dermatologists treat. You must also tell them the order to use them in. For example, I always have patients apply the retinoid over the noncomedogenic moisturizer for the first few weeks to help them adjust to the retinoid. Later, once they have passed the high-risk period of retinoid dermatitis, I move the retinoid to under the moisturizer.

Psoriasis treatment (topical) is another good example. If they are going to use a surfactant-laden soap on their skin, they will impair their barrier and absorb more of the topically applied drug. Conversely, if they use a barrier repair moisturizer, they will absorb less. Telling the patients exactly which body cleansers and moisturizers to use with topical psoriasis medications will help standardize the response. For this reason, giving patients printed regimens is not limited to treatment of acne, rosacea, and photoaging, but rather should be done for patients with all skin issues and phenotypes.

Have informational material for each phenotype at your fingertips

You can have a plan for each patient phenotype that is designed ahead of time. You will save yourself hours of time if you have preprinted instructions sheets made for each of these phenotypes. You can use Touch MD, The Canfield Visia Camera Patient Portal, your EMR, or other systems to organize this material and deliver it to patients.

I personally use the Skin Type Solutions Software System (STSFranchise.com) that I developed and patented to house and export my patient instructions. Using a standardized methodology to provide educational information through video, preprinted sheets, emails, and other methods allows you to educate your patients at their pace and in the media with which they are most comfortable. To have this flexibility, the educational information must be developed prior to the patient visit. Categorizing the education information by phenotype makes this possible.

What the informational material should contain

Educational information should include important information about the phenotype, the do’s and don’ts for the phenotype, an exact skin care regimen containing clear steps that include product names including brand names, prescription medications, the order in which the products should be applied, and clear instructions on how to use the products.

The patient should be informed about what to do if anticipated adverse events occur, such as redness and peeling from retinoids or dryness from benzoyl peroxide. The same is true about injectable biologic medications for psoriasis. The patients need information on where to inject the product, how often, how to clean the skin beforehand, and what to put on the skin after the injections. It is always important with any skin issue for the patient to know when to contact the office. The American Academy of Dermatology and other organizations offer educational brochures for patients, but they cannot be customized. Patients prefer a customized approach to educational material. They don’t want to read information that does not apply to them. I have found that dividing patients into 16 distinct Baumann Skin Types helps target the right information to the corresponding skin phenotypes.

Summary

Patients need education and guidance to be compliant and improve their outcomes. Your staff needs to be a part of the education process, but taking the time to train your staff and educate your patients is always an issue. Developing a standardized methodology will help overcome these hurdles and solve this problem. The methodology should provide directed education and clear communication with written instructions delivered in the media of the patient’s choice. Doing this will yield better compliance and outcomes.

If you have any questions, suggestions or ideas of how to solve these issues, please share them with me at [email protected].

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 wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and “Cosmeceuticals and Cosmetic Ingredients,” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems LLC.

References

1. JAMA Dermatol. 2015 Jun;151(6):623-6.

2. J Am Acad Dermatol. 2004 Aug;51(2):212-6.

3. J Am Acad Dermatol. 2007 Jul;57(1):81-3.

4. Dermatol Clin. 2008 Jul;26(3):359-73.

5. Baumann L. Cosmetics and skin care in dermatology. In: Wolff K, ed. Fitzpatrick’s Dermatology in General Medicine, 7th ed. New York, NY: McGraw-Hill; 2008:2357-2364.

6. Baumann L. The Baumann skin typing system. In: Farage MA, Miller KW, Maibach HI, eds. Textbook of Aging Skin. Berling, Germany: Springer-Verlag; 2010:929-944.

7. Journal of Cosmetics, Dermatological Sciences and Applications. 2016;6(1):34-40.

Ursolic acid (3beta-hydroxy-urs-12-en-28-oic acid) is a pentacyclic triterpenoid found naturally in apples, waxy berries, rosemary, oregano, and several other plants and herbs used in medicine and the diet.^1,2 It is known to have significant antioxidant, anti-inflammatory, and antiproliferative properties, and has also been associated with a wider range of biologic activities, including anticancer, antimicrobial, antitumor, antiwrinkle, anti-HIV, cytotoxic, and hepatoprotective.^3,4 In addition, ursolic acid is the focus of human clinical trials for potential uses in cancer and skin wrinkles.⁴ While this triterpenoid is known to suppress tumor formation and viability in various kinds of cancer, including skin cancer, several forms of cancer are resistant to ursolic acid.

RobinCraigPhoto/Thinkstock

Anti-inflammatory activity

In a 2013 study of the antibacterial and anti-inflammatory effects of Syzygium jambos on acne, Sharma et al. found that ursolic acid was one of the constituents of the leaf extracts that contributed to a significant suppression of the release of inflammatory cytokines interleukin (IL)-8 and tumor necrosis factor-alpha.⁵

In 2010, Yang et al. identified ursolic acid as a key constituent of Acanthopanax koreanum fruit, a popular fruit in Jeju Island, South Korea, extracts of which they found to exhibit significant anti-inflammatory activity and suitability as a topical agent.⁶

Yasukawa et al. conducted an in vivo two-stage carcinogenesis test in mice in 2009 in which extracts of the branches of Hippophae rhamnoides displayed significant antitumor activity after initiation with 7,12-dimethylbenz[a]anthracene (DMBA) and promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA). Ursolic acid and (-)-epigallocatechin were the constituents found to have the greatest inhibitory effects on TPA-induced inflammation.⁷

Anticancer activity

In 2015, Cho et al. reported on the inhibitory effects on skin tumor promotion from the topical application of ursolic acid, resveratrol, or the combination of the two prior to TPA treatment on mouse skin. The combination of the two botanical agents yielded the strongest suppression of TPA-induced epidermal hyperproliferation, skin inflammation, inflammatory gene expression, and skin tumor promotion.¹¹

In another study that year buttressing the combination of the two botanical agents, Junco et al. demonstrated that chloroquine could be used to sensitize B16F10 metastatic mouse melanoma to the anticancer activities of ursolic acid and resveratrol. The investigators concluded that the combination of ursolic acid or resveratrol with chloroquine has potential for inclusion in melanoma treatment in humans.¹² Previously, Junco et al. observed that the anti–skin cancer effects of ursolic acid are augmented by P-glycoprotein inhibitors, and that ursolic acid and the stilbene resveratrol, a potent antioxidant, work synergistically, although not by blocking P-glycoprotein. The investigators suggested that ursolic acid along with resveratrol and/or P-glycoprotein inhibitors have potential as effective anti–skin cancer regimens.

In 2014, Lee et al. showed that ursolic acid can differentially modulate apoptosis in cutaneous melanoma and retinal pigment epithelial cells exposed to ultraviolet to visible broadband radiation, exhibiting the potential to protect normal cells while sensitizing melanoma cells to the effects of UV radiation.¹³ These findings supported earlier work by the team showing that pretreatment of human cells derived from a malignant skin melanoma markedly enhanced the sensitivity of melanoma cells to UV radiation, while providing some photoprotection to retinal pigment epithelium.

Also that year, Soica et al. demonstrated, using in vitro tests and in vivo skin cancer models, that the mixture of oleanolic and ursolic acids and in complex with cyclodextrin rendered a synergistic antitumor activity.¹⁴

A year earlier, Kowalczyk et al. showed that the combined action of phytochemicals – dietary calcium D-glucarate and topical ursolic acid and resveratrol – was effective in suppressing the initiation (with 7,12-dimethylbenz[a]anthracene [DMBA]) and promotion (with TPA) of skin tumorigenesis in SENCAR mice. Ursolic acid alone or in combination with calcium D-glucarate significantly diminished epidermal hyperplasia when applied during promotion. All of the antipromotion protocols led to significant decreases in cyclooxygenase-2 and interleukin (IL)-6 expression. The researchers concluded that ursolic acid strongly inhibits skin tumor promotion and inflammatory signaling, and warrants attention as a potential preventive agent against skin and other epithelial cancers.¹⁵ Kowalczyk et al. had previously found that ursolic acid and other phytochemicals displayed significant in vitro and in vivo antioxidant and antitumorigenic activity, inhibiting murine skin carcinogenesis by blunting tumor initiation and tumor promotion/progression.¹⁶

In 2006, beta-ursolic acid isolated from Salvia officinalis was found by Jedinák et al. to be effective in suppressing lung colonization of beta16 mouse melanoma cells in vivo.¹⁷

Huang et al. showed in 1994 that extracts of the leaves of Rosmarinus officinalis (rosemary) were effective in suppressing tumor initiation and promotion in a two-stage skin tumorigenesis mouse model. Topically applied ursolic acid isolated from the leaves was found to hinder TPA-induced ear inflammation, ornithine decarboxylase activity, and tumor promotion. The number of tumors per mouse also declined significantly due to the topical application of ursolic acid concurrent with twice weekly application of the tumor-promoter TPA in DMBA-initiated mice.¹⁸

Antiaging and other activities

In 2015, Herndon et al. conducted an open-label clinical trial in 37 females (aged 35-60 years) to ascertain the effectiveness of an anti-aging moisturizer containing Astragalus membranaceus root extract, a peptide blend including palmitoyl tripeptide-38, standardized rosemary leaf extract (ursolic acid), tetrahexyldecyl ascorbate (THD ascorbate), and ubiquinone (coenzyme Q10). Subjects were instructed to apply the moisturizer once in the morning and once in the evening, and were assessed at baseline, and after 4, 8, and 12 weeks of twice daily application. Clinical evaluations after 8 weeks revealed a statistically significant improvement in all grading parameters (fine lines and wrinkles, clarity/brightness, visual roughness, tactile roughness, redness, hyperpigmentation, and overall appearance), with even more pronounced improvement at 12 weeks. The product was found to be mild and well tolerated, and digital photography reinforced clinical assessments and self-evaluations.¹⁹

Lee et al. reported in 2012 on in vitro results suggesting that ursolic acid was effective as an inhibitor of matrix metalloproteinase (MMP)-1 after UVB exposure and was more effective than retinoic acid.²⁰

Based on studies with hairless mice, Lim et al. found in 2007 that ursolic and oleanolic acids can enhance the recovery of skin barrier function and, via peroxisome proliferator-activated receptor-alpha, spur epidermal keratinocyte differentiation. They concluded that both acids have potential for use as agents to promote epidermal permeability barrier function.²¹

In 2003, Soo et al. observed that pretreatment with ursolic acid inhibited UVA-induced oxidative stress and activation and expression of MMP-2 in HaCaT human keratinocytes. They concluded that ursolic acid may merit attention for the prevention of UVA-induced photoaging.²²

Three years earlier, Yarosh et al. showed that liposomes containing ursolic acid augmented ceramide content in cultured normal human epidermal keratinocytes and collagen content in cultured normal human dermal fibroblasts. Over an 11-day period, clinical tests with the ursolic acid–containing liposome (Merotaine) revealed increases in the ceramide content in human skin.²³ Two years later, many of the same researchers duplicated their results. This new study also demonstrated that ursolic acid liposomes raise ceramide levels in normal human epidermal keratinocytes, in contrast to the effects of retinoic acid, earlier shown to reduce such levels. They concluded that ursolic acid liposomes show promise for use alone or in combination to replenish or maintain cutaneous ceramide and collagen levels.²⁴ Notably, ursolic acid is incorporated into topical oils and creams intended to confer rejuvenating effects to the skin.
 

Conclusion

Ursolic acid is a compelling ingredient. I especially will be interested in the results of ongoing human clinical trials of this triterpenoid for treating cancer and skin wrinkles. As it is, ursolic acid is known to exert significant inhibitory activity against tumor formation and tumor cell viability in the laboratory. Given its wide range of biologic activity, and some promising cutaneous results, there is reason to believe that ursolic acid has the potential to play an increasingly useful role in topical skin care agents and dermatologic practice.

References

1. J Dermatol. 2007 Sep;34(9):625-34.

2. Folia Histochem Cytobiol. 2011;49(4):664-9.

3. J Cosmet Dermatol. 2004 Jan;3(1):26-34.

4. J Enzyme Inhib Med Chem. 2011 Oct;26(5):616-42.

5. BMC Complement Altern Med. 2013 Oct 29;13:292.

6. J Biomed Biotechnol. 2010;2010:715739.

7. Fitoterapia. 2009 Apr;80(3):164-7.

8. Biosci Biotechnol Biochem. 2004 Jan;68(1):85-90.

9. J Ethnopharmacol. 2002 Oct;82(2-3):229-37.

10. Eur J Pharmacol. 1997 Sep 3;334(1):103-5.

11. Cancer Prev Res (Phila). 2015 Sep;8(9):817-25.

12. Melanoma Res. 2015 Apr;25(2):103-12.

13. Apoptosis. 2014 May;19(5):816-28.

14. Molecules. 2014 Apr 17;19(4):4924-40.

15. Int J Oncol. 2013 Sep;43(3):911-8.

16. Carcinogenesis. 2009 Jun;30(6):1008-15.

17. Z Naturforsch C. 2006 Nov-Dec;61(11-12):777-82.

18. Cancer Res. 1994 Feb 1;54(3):701-8.

19. J Drugs Dermatol. 2015 Jul;14(7):699-704.

20. Bioorg Khim. 2012 May-Jun;38(3):374-81.

21. J Dermatol. 2007;34(9):625-34.

22. Eur J Pharmacol. 2003 Aug 29;476(3):173-8.

23. Horm Res. 2000;54(5-6):318-21.

24. Arch Dermatol Res. 2002 Jan;293(11):569-75.

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

Ursolic acid (3beta-hydroxy-urs-12-en-28-oic acid) is a pentacyclic triterpenoid found naturally in apples, waxy berries, rosemary, oregano, and several other plants and herbs used in medicine and the diet.^1,2 It is known to have significant antioxidant, anti-inflammatory, and antiproliferative properties, and has also been associated with a wider range of biologic activities, including anticancer, antimicrobial, antitumor, antiwrinkle, anti-HIV, cytotoxic, and hepatoprotective.^3,4 In addition, ursolic acid is the focus of human clinical trials for potential uses in cancer and skin wrinkles.⁴ While this triterpenoid is known to suppress tumor formation and viability in various kinds of cancer, including skin cancer, several forms of cancer are resistant to ursolic acid.

RobinCraigPhoto/Thinkstock

Anti-inflammatory activity

In a 2013 study of the antibacterial and anti-inflammatory effects of Syzygium jambos on acne, Sharma et al. found that ursolic acid was one of the constituents of the leaf extracts that contributed to a significant suppression of the release of inflammatory cytokines interleukin (IL)-8 and tumor necrosis factor-alpha.⁵

In 2010, Yang et al. identified ursolic acid as a key constituent of Acanthopanax koreanum fruit, a popular fruit in Jeju Island, South Korea, extracts of which they found to exhibit significant anti-inflammatory activity and suitability as a topical agent.⁶

Yasukawa et al. conducted an in vivo two-stage carcinogenesis test in mice in 2009 in which extracts of the branches of Hippophae rhamnoides displayed significant antitumor activity after initiation with 7,12-dimethylbenz[a]anthracene (DMBA) and promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA). Ursolic acid and (-)-epigallocatechin were the constituents found to have the greatest inhibitory effects on TPA-induced inflammation.⁷

Anticancer activity

In 2015, Cho et al. reported on the inhibitory effects on skin tumor promotion from the topical application of ursolic acid, resveratrol, or the combination of the two prior to TPA treatment on mouse skin. The combination of the two botanical agents yielded the strongest suppression of TPA-induced epidermal hyperproliferation, skin inflammation, inflammatory gene expression, and skin tumor promotion.¹¹

In another study that year buttressing the combination of the two botanical agents, Junco et al. demonstrated that chloroquine could be used to sensitize B16F10 metastatic mouse melanoma to the anticancer activities of ursolic acid and resveratrol. The investigators concluded that the combination of ursolic acid or resveratrol with chloroquine has potential for inclusion in melanoma treatment in humans.¹² Previously, Junco et al. observed that the anti–skin cancer effects of ursolic acid are augmented by P-glycoprotein inhibitors, and that ursolic acid and the stilbene resveratrol, a potent antioxidant, work synergistically, although not by blocking P-glycoprotein. The investigators suggested that ursolic acid along with resveratrol and/or P-glycoprotein inhibitors have potential as effective anti–skin cancer regimens.

In 2014, Lee et al. showed that ursolic acid can differentially modulate apoptosis in cutaneous melanoma and retinal pigment epithelial cells exposed to ultraviolet to visible broadband radiation, exhibiting the potential to protect normal cells while sensitizing melanoma cells to the effects of UV radiation.¹³ These findings supported earlier work by the team showing that pretreatment of human cells derived from a malignant skin melanoma markedly enhanced the sensitivity of melanoma cells to UV radiation, while providing some photoprotection to retinal pigment epithelium.

Also that year, Soica et al. demonstrated, using in vitro tests and in vivo skin cancer models, that the mixture of oleanolic and ursolic acids and in complex with cyclodextrin rendered a synergistic antitumor activity.¹⁴

A year earlier, Kowalczyk et al. showed that the combined action of phytochemicals – dietary calcium D-glucarate and topical ursolic acid and resveratrol – was effective in suppressing the initiation (with 7,12-dimethylbenz[a]anthracene [DMBA]) and promotion (with TPA) of skin tumorigenesis in SENCAR mice. Ursolic acid alone or in combination with calcium D-glucarate significantly diminished epidermal hyperplasia when applied during promotion. All of the antipromotion protocols led to significant decreases in cyclooxygenase-2 and interleukin (IL)-6 expression. The researchers concluded that ursolic acid strongly inhibits skin tumor promotion and inflammatory signaling, and warrants attention as a potential preventive agent against skin and other epithelial cancers.¹⁵ Kowalczyk et al. had previously found that ursolic acid and other phytochemicals displayed significant in vitro and in vivo antioxidant and antitumorigenic activity, inhibiting murine skin carcinogenesis by blunting tumor initiation and tumor promotion/progression.¹⁶

In 2006, beta-ursolic acid isolated from Salvia officinalis was found by Jedinák et al. to be effective in suppressing lung colonization of beta16 mouse melanoma cells in vivo.¹⁷

Huang et al. showed in 1994 that extracts of the leaves of Rosmarinus officinalis (rosemary) were effective in suppressing tumor initiation and promotion in a two-stage skin tumorigenesis mouse model. Topically applied ursolic acid isolated from the leaves was found to hinder TPA-induced ear inflammation, ornithine decarboxylase activity, and tumor promotion. The number of tumors per mouse also declined significantly due to the topical application of ursolic acid concurrent with twice weekly application of the tumor-promoter TPA in DMBA-initiated mice.¹⁸

Antiaging and other activities

In 2015, Herndon et al. conducted an open-label clinical trial in 37 females (aged 35-60 years) to ascertain the effectiveness of an anti-aging moisturizer containing Astragalus membranaceus root extract, a peptide blend including palmitoyl tripeptide-38, standardized rosemary leaf extract (ursolic acid), tetrahexyldecyl ascorbate (THD ascorbate), and ubiquinone (coenzyme Q10). Subjects were instructed to apply the moisturizer once in the morning and once in the evening, and were assessed at baseline, and after 4, 8, and 12 weeks of twice daily application. Clinical evaluations after 8 weeks revealed a statistically significant improvement in all grading parameters (fine lines and wrinkles, clarity/brightness, visual roughness, tactile roughness, redness, hyperpigmentation, and overall appearance), with even more pronounced improvement at 12 weeks. The product was found to be mild and well tolerated, and digital photography reinforced clinical assessments and self-evaluations.¹⁹

Lee et al. reported in 2012 on in vitro results suggesting that ursolic acid was effective as an inhibitor of matrix metalloproteinase (MMP)-1 after UVB exposure and was more effective than retinoic acid.²⁰

Based on studies with hairless mice, Lim et al. found in 2007 that ursolic and oleanolic acids can enhance the recovery of skin barrier function and, via peroxisome proliferator-activated receptor-alpha, spur epidermal keratinocyte differentiation. They concluded that both acids have potential for use as agents to promote epidermal permeability barrier function.²¹

In 2003, Soo et al. observed that pretreatment with ursolic acid inhibited UVA-induced oxidative stress and activation and expression of MMP-2 in HaCaT human keratinocytes. They concluded that ursolic acid may merit attention for the prevention of UVA-induced photoaging.²²

Three years earlier, Yarosh et al. showed that liposomes containing ursolic acid augmented ceramide content in cultured normal human epidermal keratinocytes and collagen content in cultured normal human dermal fibroblasts. Over an 11-day period, clinical tests with the ursolic acid–containing liposome (Merotaine) revealed increases in the ceramide content in human skin.²³ Two years later, many of the same researchers duplicated their results. This new study also demonstrated that ursolic acid liposomes raise ceramide levels in normal human epidermal keratinocytes, in contrast to the effects of retinoic acid, earlier shown to reduce such levels. They concluded that ursolic acid liposomes show promise for use alone or in combination to replenish or maintain cutaneous ceramide and collagen levels.²⁴ Notably, ursolic acid is incorporated into topical oils and creams intended to confer rejuvenating effects to the skin.
 

Conclusion

Ursolic acid is a compelling ingredient. I especially will be interested in the results of ongoing human clinical trials of this triterpenoid for treating cancer and skin wrinkles. As it is, ursolic acid is known to exert significant inhibitory activity against tumor formation and tumor cell viability in the laboratory. Given its wide range of biologic activity, and some promising cutaneous results, there is reason to believe that ursolic acid has the potential to play an increasingly useful role in topical skin care agents and dermatologic practice.

References

1. J Dermatol. 2007 Sep;34(9):625-34.

2. Folia Histochem Cytobiol. 2011;49(4):664-9.

3. J Cosmet Dermatol. 2004 Jan;3(1):26-34.

4. J Enzyme Inhib Med Chem. 2011 Oct;26(5):616-42.

5. BMC Complement Altern Med. 2013 Oct 29;13:292.

6. J Biomed Biotechnol. 2010;2010:715739.

7. Fitoterapia. 2009 Apr;80(3):164-7.

8. Biosci Biotechnol Biochem. 2004 Jan;68(1):85-90.

9. J Ethnopharmacol. 2002 Oct;82(2-3):229-37.

10. Eur J Pharmacol. 1997 Sep 3;334(1):103-5.

11. Cancer Prev Res (Phila). 2015 Sep;8(9):817-25.

12. Melanoma Res. 2015 Apr;25(2):103-12.

13. Apoptosis. 2014 May;19(5):816-28.

14. Molecules. 2014 Apr 17;19(4):4924-40.

15. Int J Oncol. 2013 Sep;43(3):911-8.

16. Carcinogenesis. 2009 Jun;30(6):1008-15.

17. Z Naturforsch C. 2006 Nov-Dec;61(11-12):777-82.

18. Cancer Res. 1994 Feb 1;54(3):701-8.

19. J Drugs Dermatol. 2015 Jul;14(7):699-704.

20. Bioorg Khim. 2012 May-Jun;38(3):374-81.

21. J Dermatol. 2007;34(9):625-34.

22. Eur J Pharmacol. 2003 Aug 29;476(3):173-8.

23. Horm Res. 2000;54(5-6):318-21.

24. Arch Dermatol Res. 2002 Jan;293(11):569-75.

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

Ursolic acid (3beta-hydroxy-urs-12-en-28-oic acid) is a pentacyclic triterpenoid found naturally in apples, waxy berries, rosemary, oregano, and several other plants and herbs used in medicine and the diet.^1,2 It is known to have significant antioxidant, anti-inflammatory, and antiproliferative properties, and has also been associated with a wider range of biologic activities, including anticancer, antimicrobial, antitumor, antiwrinkle, anti-HIV, cytotoxic, and hepatoprotective.^3,4 In addition, ursolic acid is the focus of human clinical trials for potential uses in cancer and skin wrinkles.⁴ While this triterpenoid is known to suppress tumor formation and viability in various kinds of cancer, including skin cancer, several forms of cancer are resistant to ursolic acid.

RobinCraigPhoto/Thinkstock

Anti-inflammatory activity

In a 2013 study of the antibacterial and anti-inflammatory effects of Syzygium jambos on acne, Sharma et al. found that ursolic acid was one of the constituents of the leaf extracts that contributed to a significant suppression of the release of inflammatory cytokines interleukin (IL)-8 and tumor necrosis factor-alpha.⁵

In 2010, Yang et al. identified ursolic acid as a key constituent of Acanthopanax koreanum fruit, a popular fruit in Jeju Island, South Korea, extracts of which they found to exhibit significant anti-inflammatory activity and suitability as a topical agent.⁶

Yasukawa et al. conducted an in vivo two-stage carcinogenesis test in mice in 2009 in which extracts of the branches of Hippophae rhamnoides displayed significant antitumor activity after initiation with 7,12-dimethylbenz[a]anthracene (DMBA) and promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA). Ursolic acid and (-)-epigallocatechin were the constituents found to have the greatest inhibitory effects on TPA-induced inflammation.⁷

Anticancer activity

In 2015, Cho et al. reported on the inhibitory effects on skin tumor promotion from the topical application of ursolic acid, resveratrol, or the combination of the two prior to TPA treatment on mouse skin. The combination of the two botanical agents yielded the strongest suppression of TPA-induced epidermal hyperproliferation, skin inflammation, inflammatory gene expression, and skin tumor promotion.¹¹

In another study that year buttressing the combination of the two botanical agents, Junco et al. demonstrated that chloroquine could be used to sensitize B16F10 metastatic mouse melanoma to the anticancer activities of ursolic acid and resveratrol. The investigators concluded that the combination of ursolic acid or resveratrol with chloroquine has potential for inclusion in melanoma treatment in humans.¹² Previously, Junco et al. observed that the anti–skin cancer effects of ursolic acid are augmented by P-glycoprotein inhibitors, and that ursolic acid and the stilbene resveratrol, a potent antioxidant, work synergistically, although not by blocking P-glycoprotein. The investigators suggested that ursolic acid along with resveratrol and/or P-glycoprotein inhibitors have potential as effective anti–skin cancer regimens.

In 2014, Lee et al. showed that ursolic acid can differentially modulate apoptosis in cutaneous melanoma and retinal pigment epithelial cells exposed to ultraviolet to visible broadband radiation, exhibiting the potential to protect normal cells while sensitizing melanoma cells to the effects of UV radiation.¹³ These findings supported earlier work by the team showing that pretreatment of human cells derived from a malignant skin melanoma markedly enhanced the sensitivity of melanoma cells to UV radiation, while providing some photoprotection to retinal pigment epithelium.

Also that year, Soica et al. demonstrated, using in vitro tests and in vivo skin cancer models, that the mixture of oleanolic and ursolic acids and in complex with cyclodextrin rendered a synergistic antitumor activity.¹⁴

A year earlier, Kowalczyk et al. showed that the combined action of phytochemicals – dietary calcium D-glucarate and topical ursolic acid and resveratrol – was effective in suppressing the initiation (with 7,12-dimethylbenz[a]anthracene [DMBA]) and promotion (with TPA) of skin tumorigenesis in SENCAR mice. Ursolic acid alone or in combination with calcium D-glucarate significantly diminished epidermal hyperplasia when applied during promotion. All of the antipromotion protocols led to significant decreases in cyclooxygenase-2 and interleukin (IL)-6 expression. The researchers concluded that ursolic acid strongly inhibits skin tumor promotion and inflammatory signaling, and warrants attention as a potential preventive agent against skin and other epithelial cancers.¹⁵ Kowalczyk et al. had previously found that ursolic acid and other phytochemicals displayed significant in vitro and in vivo antioxidant and antitumorigenic activity, inhibiting murine skin carcinogenesis by blunting tumor initiation and tumor promotion/progression.¹⁶

In 2006, beta-ursolic acid isolated from Salvia officinalis was found by Jedinák et al. to be effective in suppressing lung colonization of beta16 mouse melanoma cells in vivo.¹⁷

Huang et al. showed in 1994 that extracts of the leaves of Rosmarinus officinalis (rosemary) were effective in suppressing tumor initiation and promotion in a two-stage skin tumorigenesis mouse model. Topically applied ursolic acid isolated from the leaves was found to hinder TPA-induced ear inflammation, ornithine decarboxylase activity, and tumor promotion. The number of tumors per mouse also declined significantly due to the topical application of ursolic acid concurrent with twice weekly application of the tumor-promoter TPA in DMBA-initiated mice.¹⁸

Antiaging and other activities

In 2015, Herndon et al. conducted an open-label clinical trial in 37 females (aged 35-60 years) to ascertain the effectiveness of an anti-aging moisturizer containing Astragalus membranaceus root extract, a peptide blend including palmitoyl tripeptide-38, standardized rosemary leaf extract (ursolic acid), tetrahexyldecyl ascorbate (THD ascorbate), and ubiquinone (coenzyme Q10). Subjects were instructed to apply the moisturizer once in the morning and once in the evening, and were assessed at baseline, and after 4, 8, and 12 weeks of twice daily application. Clinical evaluations after 8 weeks revealed a statistically significant improvement in all grading parameters (fine lines and wrinkles, clarity/brightness, visual roughness, tactile roughness, redness, hyperpigmentation, and overall appearance), with even more pronounced improvement at 12 weeks. The product was found to be mild and well tolerated, and digital photography reinforced clinical assessments and self-evaluations.¹⁹

Lee et al. reported in 2012 on in vitro results suggesting that ursolic acid was effective as an inhibitor of matrix metalloproteinase (MMP)-1 after UVB exposure and was more effective than retinoic acid.²⁰

Based on studies with hairless mice, Lim et al. found in 2007 that ursolic and oleanolic acids can enhance the recovery of skin barrier function and, via peroxisome proliferator-activated receptor-alpha, spur epidermal keratinocyte differentiation. They concluded that both acids have potential for use as agents to promote epidermal permeability barrier function.²¹

In 2003, Soo et al. observed that pretreatment with ursolic acid inhibited UVA-induced oxidative stress and activation and expression of MMP-2 in HaCaT human keratinocytes. They concluded that ursolic acid may merit attention for the prevention of UVA-induced photoaging.²²

Three years earlier, Yarosh et al. showed that liposomes containing ursolic acid augmented ceramide content in cultured normal human epidermal keratinocytes and collagen content in cultured normal human dermal fibroblasts. Over an 11-day period, clinical tests with the ursolic acid–containing liposome (Merotaine) revealed increases in the ceramide content in human skin.²³ Two years later, many of the same researchers duplicated their results. This new study also demonstrated that ursolic acid liposomes raise ceramide levels in normal human epidermal keratinocytes, in contrast to the effects of retinoic acid, earlier shown to reduce such levels. They concluded that ursolic acid liposomes show promise for use alone or in combination to replenish or maintain cutaneous ceramide and collagen levels.²⁴ Notably, ursolic acid is incorporated into topical oils and creams intended to confer rejuvenating effects to the skin.
 

Conclusion

Ursolic acid is a compelling ingredient. I especially will be interested in the results of ongoing human clinical trials of this triterpenoid for treating cancer and skin wrinkles. As it is, ursolic acid is known to exert significant inhibitory activity against tumor formation and tumor cell viability in the laboratory. Given its wide range of biologic activity, and some promising cutaneous results, there is reason to believe that ursolic acid has the potential to play an increasingly useful role in topical skin care agents and dermatologic practice.

References

1. J Dermatol. 2007 Sep;34(9):625-34.

2. Folia Histochem Cytobiol. 2011;49(4):664-9.

3. J Cosmet Dermatol. 2004 Jan;3(1):26-34.

4. J Enzyme Inhib Med Chem. 2011 Oct;26(5):616-42.

5. BMC Complement Altern Med. 2013 Oct 29;13:292.

6. J Biomed Biotechnol. 2010;2010:715739.

7. Fitoterapia. 2009 Apr;80(3):164-7.

8. Biosci Biotechnol Biochem. 2004 Jan;68(1):85-90.

9. J Ethnopharmacol. 2002 Oct;82(2-3):229-37.

10. Eur J Pharmacol. 1997 Sep 3;334(1):103-5.

11. Cancer Prev Res (Phila). 2015 Sep;8(9):817-25.

12. Melanoma Res. 2015 Apr;25(2):103-12.

13. Apoptosis. 2014 May;19(5):816-28.

14. Molecules. 2014 Apr 17;19(4):4924-40.

15. Int J Oncol. 2013 Sep;43(3):911-8.

16. Carcinogenesis. 2009 Jun;30(6):1008-15.

17. Z Naturforsch C. 2006 Nov-Dec;61(11-12):777-82.

18. Cancer Res. 1994 Feb 1;54(3):701-8.

19. J Drugs Dermatol. 2015 Jul;14(7):699-704.

20. Bioorg Khim. 2012 May-Jun;38(3):374-81.

21. J Dermatol. 2007;34(9):625-34.

22. Eur J Pharmacol. 2003 Aug 29;476(3):173-8.

23. Horm Res. 2000;54(5-6):318-21.

24. Arch Dermatol Res. 2002 Jan;293(11):569-75.

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

The discussion this month focuses on an exciting new ingredient that is showing great promise as a topical antiaging agent. For years we have known that aging skin needs more collagen, elastin, and hyaluronic acid. It is time to add a new player to the antiaging team – heparan sulfate (HS). New studies have shown that lower levels of HS are associated with aged skin. This is what you need to know.

Significance of HS

Endogenous HS, an essential glycosaminoglycan (GAG), contributes to skin development and homeostasis, and thus actively promotes skin health.¹ GAGs such as HS and hyaluronic acid are well known as endogenous superhydrators that bind and retain water, thus contributing to skin hydration as well as preserving the structural integrity of collagen and elastin fibers. Specifically, HS and its protein-bound forms (HS proteoglycans such as syndecan, glypican, and perlecan) – the most common constituents on the cell surface and in the extracellular matrix (ECM) – play an important role in cutaneous cell proliferation, migration, communication, and activation as well as collagen fiber development, basement membrane regeneration, granulation tissue formation, and cell adhesion related to wound healing.¹ This results from their capacity to bind, store, present, degrade, and amplify growth factors and cytokines.

Conclusion

Heparan sulfate does appear to be a novel viable antiaging option. Endogenous heparan sulfate is involved in skin defense against pathogens, dehydrated/dried skin, redness, and wound healing. Theoretically, then, HS analogs should be able to modulate these processes. More research is necessary to determine if this is the case, however. In the meantime, HS analogs are extremely well tolerated by all patients and especially those with sensitive skin, which is often the case with aging skin. Further, HS analogs promote skin hydration, providing resistance to compressive forces as well as keeping skin looking healthy. Anecdotally, I can report that I have been using the Senté Dermal Repair Cream in my rosacea patients without any problems. I think HS analogs represent a good option for patients who cannot tolerate retinoids.

Resources

1. J Drugs Dermatol. 2015 Jul;14(7):669-74.

2. Proteoglycans in Skin Aging, in “Textbook of Aging Skin” (Heidelberg, Berlin: Springer-Verlag, pp. 109-120).

3. Joint Bone Spine. 2016 Sep 20. doi: 10.1016/j.jbspin.2016.06.012.

4. Ann Chir Plast Esthet. 2010 Oct;55(5):421-8.

5. Int Wound J. 2015 Apr;12(2):169-72.

6. Int Wound J. 2016 Feb;13(1):35-8.

7. ISRN Orthop. 2012 Jan 17. doi: 10.5402/2012/504151.

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

The discussion this month focuses on an exciting new ingredient that is showing great promise as a topical antiaging agent. For years we have known that aging skin needs more collagen, elastin, and hyaluronic acid. It is time to add a new player to the antiaging team – heparan sulfate (HS). New studies have shown that lower levels of HS are associated with aged skin. This is what you need to know.

Significance of HS

Endogenous HS, an essential glycosaminoglycan (GAG), contributes to skin development and homeostasis, and thus actively promotes skin health.¹ GAGs such as HS and hyaluronic acid are well known as endogenous superhydrators that bind and retain water, thus contributing to skin hydration as well as preserving the structural integrity of collagen and elastin fibers. Specifically, HS and its protein-bound forms (HS proteoglycans such as syndecan, glypican, and perlecan) – the most common constituents on the cell surface and in the extracellular matrix (ECM) – play an important role in cutaneous cell proliferation, migration, communication, and activation as well as collagen fiber development, basement membrane regeneration, granulation tissue formation, and cell adhesion related to wound healing.¹ This results from their capacity to bind, store, present, degrade, and amplify growth factors and cytokines.

Conclusion

Heparan sulfate does appear to be a novel viable antiaging option. Endogenous heparan sulfate is involved in skin defense against pathogens, dehydrated/dried skin, redness, and wound healing. Theoretically, then, HS analogs should be able to modulate these processes. More research is necessary to determine if this is the case, however. In the meantime, HS analogs are extremely well tolerated by all patients and especially those with sensitive skin, which is often the case with aging skin. Further, HS analogs promote skin hydration, providing resistance to compressive forces as well as keeping skin looking healthy. Anecdotally, I can report that I have been using the Senté Dermal Repair Cream in my rosacea patients without any problems. I think HS analogs represent a good option for patients who cannot tolerate retinoids.

Resources

1. J Drugs Dermatol. 2015 Jul;14(7):669-74.

2. Proteoglycans in Skin Aging, in “Textbook of Aging Skin” (Heidelberg, Berlin: Springer-Verlag, pp. 109-120).

3. Joint Bone Spine. 2016 Sep 20. doi: 10.1016/j.jbspin.2016.06.012.

4. Ann Chir Plast Esthet. 2010 Oct;55(5):421-8.

5. Int Wound J. 2015 Apr;12(2):169-72.

6. Int Wound J. 2016 Feb;13(1):35-8.

7. ISRN Orthop. 2012 Jan 17. doi: 10.5402/2012/504151.

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

The discussion this month focuses on an exciting new ingredient that is showing great promise as a topical antiaging agent. For years we have known that aging skin needs more collagen, elastin, and hyaluronic acid. It is time to add a new player to the antiaging team – heparan sulfate (HS). New studies have shown that lower levels of HS are associated with aged skin. This is what you need to know.

Significance of HS

Endogenous HS, an essential glycosaminoglycan (GAG), contributes to skin development and homeostasis, and thus actively promotes skin health.¹ GAGs such as HS and hyaluronic acid are well known as endogenous superhydrators that bind and retain water, thus contributing to skin hydration as well as preserving the structural integrity of collagen and elastin fibers. Specifically, HS and its protein-bound forms (HS proteoglycans such as syndecan, glypican, and perlecan) – the most common constituents on the cell surface and in the extracellular matrix (ECM) – play an important role in cutaneous cell proliferation, migration, communication, and activation as well as collagen fiber development, basement membrane regeneration, granulation tissue formation, and cell adhesion related to wound healing.¹ This results from their capacity to bind, store, present, degrade, and amplify growth factors and cytokines.

Conclusion

Heparan sulfate does appear to be a novel viable antiaging option. Endogenous heparan sulfate is involved in skin defense against pathogens, dehydrated/dried skin, redness, and wound healing. Theoretically, then, HS analogs should be able to modulate these processes. More research is necessary to determine if this is the case, however. In the meantime, HS analogs are extremely well tolerated by all patients and especially those with sensitive skin, which is often the case with aging skin. Further, HS analogs promote skin hydration, providing resistance to compressive forces as well as keeping skin looking healthy. Anecdotally, I can report that I have been using the Senté Dermal Repair Cream in my rosacea patients without any problems. I think HS analogs represent a good option for patients who cannot tolerate retinoids.

Resources

1. J Drugs Dermatol. 2015 Jul;14(7):669-74.

2. Proteoglycans in Skin Aging, in “Textbook of Aging Skin” (Heidelberg, Berlin: Springer-Verlag, pp. 109-120).

3. Joint Bone Spine. 2016 Sep 20. doi: 10.1016/j.jbspin.2016.06.012.

4. Ann Chir Plast Esthet. 2010 Oct;55(5):421-8.

5. Int Wound J. 2015 Apr;12(2):169-72.

6. Int Wound J. 2016 Feb;13(1):35-8.

7. ISRN Orthop. 2012 Jan 17. doi: 10.5402/2012/504151.

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

Gluten-free food products have inundated the marketplace in recent years as the food industry has responded to greater awareness of celiac sprue disease and wheat sensitivity. Gluten is the primary form of wheat protein.

Wheat is a versatile and globally popular member of the Poaceae or Gramineae family known as grasses; it is of the Triticum species with Triticum aestivum and Triticum vulgare being particularly pervasive.¹ In traditional Iranian medicine, the topical application of wheat germ oil has been used to treat psoriasis.²

Moisturization

In 2008, N. Akhtar and Y. Yazan investigated the effects of a stable emulsion containing two ingredients included to exert anti-aging effects: vitamin C and wheat protein. The antioxidant vitamin C was entrapped in the inner aqueous phase of the water-in-oil-in-water emulsion while wheat protein was incorporated in the oily phase. The investigators prepared and applied stable emulsions to the cheeks of 11 volunteers over 4 weeks, finding that the formulation increased skin moisture.⁷

Melanoma and wheat supplementation

Demidov et al. reported in 2008 on a randomized, pilot, phase II clinical trial to assess the impact of the adjuvant use of a fermented wheat germ extract nutraceutical (Avemar) in high-risk cutaneous melanoma patients. Investigators compared the efficacy of dacarbazine-based adjuvant chemotherapy on survival parameters of melanoma patients to that of the identical treatment supplemented with a 1-year administration of fermented wheat germ extract nutraceutical (FWGE), which is generally recognized as safe. They reported that after a 7-year follow-up, significant differences favoring the nutraceutical group were observed in progression-free and overall survival. Including nutraceutical as an adjuvant treatment for such patients was recommended by the authors.⁸

Telekes et al. noted that nutraceutical is registered as a special nutriment for cancer patients in Hungary that has exhibited potent anticancer activity on cell lines and immunomodulatory activity in vivo.⁹ In 2005, Boros et al. reported that orally administered FWGE suppressed metastatic tumor dissemination and proliferation during and after chemotherapy, surgery, or radiation, with benefits seen in some human cancers and cultured cells as well as some autoimmune disorders and in chemical carcinogenesis prevention.¹⁰

Hypersensitivity and allergic reactions

The risks of sensitization to topical wheat proteins are thought to be higher in patients with atopic dermatitis, who have an impaired skin barrier.¹ Indeed, Codreanu et al. have suggested that topical products containing food proteins of known allergenicity (including wheat) are contraindicated for neonates and infants with atopic dermatitis.¹¹

In 2015, Bonciolini et al. studied 17 patients (13 females and 4 males, median age 36 years) with nonceliac gluten sensitivity presenting with nonspecific skin lesions. The eczema-, psoriasis-, or dermatitis herpetiformis-like lesions on the extensor surfaces of the upper and lower limbs, especially, were confirmed histologically, but immunopathological evaluations revealed pervasive C3 deposits along the dermoepidermal junction in a microgranular/granular pattern (82%). Notably, all of the patients improved markedly after initiating a gluten-free diet.¹²

In 2014, Fukutomi et al. conducted a case-control study of Japanese women aged 20-54 years (157 cases) who self-reported wheat allergy to ascertain the epidemiologic relationship between food allergy to wheat after exposure to facial soaps containing hydrolyzed wheat protein. There were 449 age-matched controls without wheat allergy. Participants answered a Web-based questionnaire about their use of skin and hair care products. The investigators found that current use of the facial soap Cha no Shizuku (Drop of Tea), which contains hydrolyzed wheat protein, was significantly linked to a greater risk of wheat allergy, with use of the soap more frequent in consumers whose wheat allergy had newly emerged (11% vs. 6% in controls).¹³

Cha no Shizuku had earlier been implicated in provoking hundreds of cases of allergic reactions between 2009 and June 2013. R. Teshima noted that the soap contains acid-hydrolyzed wheat protein produced from gluten after partial hydrolysis with hydrogen chloride at 95 ° C for 40 minutes.¹⁴

It is worth noting that case reports of allergic reactions to facial soap containing hydrolyzed wheat protein continue to appear. Iseki et al. described in 2014 a 38-year-old woman who experienced irregular headaches, sleepiness, and an episode of facial rash eruption after daily use for about 1 year of a facial soap with hydrolyzed wheat proteins (Glupearl 19s, which is also used in Cha no Shizuku). The investigators added that the patient’s serum contained wheat-specific IgE antibodies. Symptoms disappeared after the patient abstained from wheat.¹⁵

In 2012, Tammaro studied cutaneous hypersensitivity to gluten in 14 female patients (aged 12-60 years) with celiac disease who presented with eczema on the face, neck, and arms, after topical application of gluten-containing emollient cream, bath or face powder, or contact with foods containing wheat and durum. Five of the patients tested positive for wheat and durum wheat, while none of the 14 control patients tested positive. Improvement in cutaneous lesions, with no relapses during a 6-month follow-up, resulted when these patients used gluten-free cream and bath powder, and wore gloves before handling wheat-containing food.¹⁶

In 2011, Celakovská et al. studied the impact of wheat allergy in 179 adults with atopic eczema (128 females, 51 males; average age 26 years), using open exposure and double-blind, placebo-controlled food challenge tests, as well as specific serum IgE, skin prick, and atopy patch tests. The double-blind, placebo-controlled food challenge test showed that the course of atopic eczema was exacerbated by wheat allergy in eight patients (4.5%). A positive trend revealing that the course of atopic eczema was impacted by wheat allergy emerged during follow-up (at 3, 6, 9, and 12 months).¹⁷

Contact urticaria also has been reported to have been induced by hydrolyzed wheat proteins in cosmetics and is notable for the potential to precede food allergies.^2,3 A wide variety of protein hydrolysates found in hair products have been associated with inducing contact urticaria, particularly in patients with atopic dermatitis.⁴

In 2006, Laurière et al. studied nine female patients without common wheat allergy who presented with contact urticaria to cosmetics containing hydrolyzed wheat proteins; six also had experienced generalized urticaria or anaphylaxis in response to foods containing such wheat proteins. Analyses revealed the importance of hydrolysis in augmenting the allergenicity of wheat proteins through contact or consumption.¹⁸ Immediate contact urticaria in reaction to hydrolyzed wheat protein in topical products also has been reported in a child.¹⁹

Conclusion

Can the presence of wheat hydrolysates in personal care products adversely affect a patient with celiac sprue or wheat sensitivity? The short answer appears to be “yes.” Given the use of hydrolyzed wheat protein in various skin care products, it is important that consumers who have celiac disease or sensitivity to wheat be advised to avoid skin care formulations with such active ingredients. On the positive side of the wheat ledger, there are some indications (albeit in very limited research) that the plant protein may impart beneficial health effects. Much more research is necessary to delineate the full impact of wheat on skin health.

I thank my dermatologist colleague Sharon E. Jacob, MD, at the University of Miami, for suggesting this topic.

References

1. Dermatitis. 2013 Nov-Dec;24(6):291-5.

2. Iran J Med Sci. 2016 May;41(3 Suppl):S54.

3. Contact Dermatitis. 2007 Feb;56(2):119-20.

4. Ann Dermatol Venereol. 2010 Apr;137(4):281-4.

5. Allergy. 1998 Nov;53(11):1078-82.

6. J Drugs Dermatol. 2013 Sep;12(9 Suppl):s133-6.

7. Pak J Pharm Sci. 2008 Jan;21(1):45-50.

8. Cancer Biother Radiopharm. 2008 Aug;23(4):477-82.

9. Nutr Cancer. 2009;61(6):891-9.

10. Ann N Y Acad Sci. 2005 Jun;1051:529-42.

11. Eur Ann Allergy Clin Immunol. 2006 Apr;38(4):126-30.

12. Nutrients. 2015 Sep 15;7(9):7798-805.

13. Allergy. 2014 Oct;69(10):1405-11.

14. Yakugaku Zasshi. 2014;134(1):33-8.

15. Intern Med. 2014;53(2):151-4.

16. Dermatitis. 2012 Sep-Oct;23(5):220-1.

17. Acta Medica (Hradec Kralove). 2011;54(4):157-62.

18. Contact Dermatitis. 2006 May;54(5):283-9.

19. Contact Dermatitis. 2013 Jun;68(6):379-80.

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

Gluten-free food products have inundated the marketplace in recent years as the food industry has responded to greater awareness of celiac sprue disease and wheat sensitivity. Gluten is the primary form of wheat protein.

Wheat is a versatile and globally popular member of the Poaceae or Gramineae family known as grasses; it is of the Triticum species with Triticum aestivum and Triticum vulgare being particularly pervasive.¹ In traditional Iranian medicine, the topical application of wheat germ oil has been used to treat psoriasis.²

Moisturization

In 2008, N. Akhtar and Y. Yazan investigated the effects of a stable emulsion containing two ingredients included to exert anti-aging effects: vitamin C and wheat protein. The antioxidant vitamin C was entrapped in the inner aqueous phase of the water-in-oil-in-water emulsion while wheat protein was incorporated in the oily phase. The investigators prepared and applied stable emulsions to the cheeks of 11 volunteers over 4 weeks, finding that the formulation increased skin moisture.⁷

Melanoma and wheat supplementation

Demidov et al. reported in 2008 on a randomized, pilot, phase II clinical trial to assess the impact of the adjuvant use of a fermented wheat germ extract nutraceutical (Avemar) in high-risk cutaneous melanoma patients. Investigators compared the efficacy of dacarbazine-based adjuvant chemotherapy on survival parameters of melanoma patients to that of the identical treatment supplemented with a 1-year administration of fermented wheat germ extract nutraceutical (FWGE), which is generally recognized as safe. They reported that after a 7-year follow-up, significant differences favoring the nutraceutical group were observed in progression-free and overall survival. Including nutraceutical as an adjuvant treatment for such patients was recommended by the authors.⁸

Telekes et al. noted that nutraceutical is registered as a special nutriment for cancer patients in Hungary that has exhibited potent anticancer activity on cell lines and immunomodulatory activity in vivo.⁹ In 2005, Boros et al. reported that orally administered FWGE suppressed metastatic tumor dissemination and proliferation during and after chemotherapy, surgery, or radiation, with benefits seen in some human cancers and cultured cells as well as some autoimmune disorders and in chemical carcinogenesis prevention.¹⁰

Hypersensitivity and allergic reactions

The risks of sensitization to topical wheat proteins are thought to be higher in patients with atopic dermatitis, who have an impaired skin barrier.¹ Indeed, Codreanu et al. have suggested that topical products containing food proteins of known allergenicity (including wheat) are contraindicated for neonates and infants with atopic dermatitis.¹¹

In 2015, Bonciolini et al. studied 17 patients (13 females and 4 males, median age 36 years) with nonceliac gluten sensitivity presenting with nonspecific skin lesions. The eczema-, psoriasis-, or dermatitis herpetiformis-like lesions on the extensor surfaces of the upper and lower limbs, especially, were confirmed histologically, but immunopathological evaluations revealed pervasive C3 deposits along the dermoepidermal junction in a microgranular/granular pattern (82%). Notably, all of the patients improved markedly after initiating a gluten-free diet.¹²

In 2014, Fukutomi et al. conducted a case-control study of Japanese women aged 20-54 years (157 cases) who self-reported wheat allergy to ascertain the epidemiologic relationship between food allergy to wheat after exposure to facial soaps containing hydrolyzed wheat protein. There were 449 age-matched controls without wheat allergy. Participants answered a Web-based questionnaire about their use of skin and hair care products. The investigators found that current use of the facial soap Cha no Shizuku (Drop of Tea), which contains hydrolyzed wheat protein, was significantly linked to a greater risk of wheat allergy, with use of the soap more frequent in consumers whose wheat allergy had newly emerged (11% vs. 6% in controls).¹³

Cha no Shizuku had earlier been implicated in provoking hundreds of cases of allergic reactions between 2009 and June 2013. R. Teshima noted that the soap contains acid-hydrolyzed wheat protein produced from gluten after partial hydrolysis with hydrogen chloride at 95 ° C for 40 minutes.¹⁴

It is worth noting that case reports of allergic reactions to facial soap containing hydrolyzed wheat protein continue to appear. Iseki et al. described in 2014 a 38-year-old woman who experienced irregular headaches, sleepiness, and an episode of facial rash eruption after daily use for about 1 year of a facial soap with hydrolyzed wheat proteins (Glupearl 19s, which is also used in Cha no Shizuku). The investigators added that the patient’s serum contained wheat-specific IgE antibodies. Symptoms disappeared after the patient abstained from wheat.¹⁵

In 2012, Tammaro studied cutaneous hypersensitivity to gluten in 14 female patients (aged 12-60 years) with celiac disease who presented with eczema on the face, neck, and arms, after topical application of gluten-containing emollient cream, bath or face powder, or contact with foods containing wheat and durum. Five of the patients tested positive for wheat and durum wheat, while none of the 14 control patients tested positive. Improvement in cutaneous lesions, with no relapses during a 6-month follow-up, resulted when these patients used gluten-free cream and bath powder, and wore gloves before handling wheat-containing food.¹⁶

In 2011, Celakovská et al. studied the impact of wheat allergy in 179 adults with atopic eczema (128 females, 51 males; average age 26 years), using open exposure and double-blind, placebo-controlled food challenge tests, as well as specific serum IgE, skin prick, and atopy patch tests. The double-blind, placebo-controlled food challenge test showed that the course of atopic eczema was exacerbated by wheat allergy in eight patients (4.5%). A positive trend revealing that the course of atopic eczema was impacted by wheat allergy emerged during follow-up (at 3, 6, 9, and 12 months).¹⁷

Contact urticaria also has been reported to have been induced by hydrolyzed wheat proteins in cosmetics and is notable for the potential to precede food allergies.^2,3 A wide variety of protein hydrolysates found in hair products have been associated with inducing contact urticaria, particularly in patients with atopic dermatitis.⁴

In 2006, Laurière et al. studied nine female patients without common wheat allergy who presented with contact urticaria to cosmetics containing hydrolyzed wheat proteins; six also had experienced generalized urticaria or anaphylaxis in response to foods containing such wheat proteins. Analyses revealed the importance of hydrolysis in augmenting the allergenicity of wheat proteins through contact or consumption.¹⁸ Immediate contact urticaria in reaction to hydrolyzed wheat protein in topical products also has been reported in a child.¹⁹

Conclusion

Can the presence of wheat hydrolysates in personal care products adversely affect a patient with celiac sprue or wheat sensitivity? The short answer appears to be “yes.” Given the use of hydrolyzed wheat protein in various skin care products, it is important that consumers who have celiac disease or sensitivity to wheat be advised to avoid skin care formulations with such active ingredients. On the positive side of the wheat ledger, there are some indications (albeit in very limited research) that the plant protein may impart beneficial health effects. Much more research is necessary to delineate the full impact of wheat on skin health.

I thank my dermatologist colleague Sharon E. Jacob, MD, at the University of Miami, for suggesting this topic.

References

1. Dermatitis. 2013 Nov-Dec;24(6):291-5.

2. Iran J Med Sci. 2016 May;41(3 Suppl):S54.

3. Contact Dermatitis. 2007 Feb;56(2):119-20.

4. Ann Dermatol Venereol. 2010 Apr;137(4):281-4.

5. Allergy. 1998 Nov;53(11):1078-82.

6. J Drugs Dermatol. 2013 Sep;12(9 Suppl):s133-6.

7. Pak J Pharm Sci. 2008 Jan;21(1):45-50.

8. Cancer Biother Radiopharm. 2008 Aug;23(4):477-82.

9. Nutr Cancer. 2009;61(6):891-9.

10. Ann N Y Acad Sci. 2005 Jun;1051:529-42.

11. Eur Ann Allergy Clin Immunol. 2006 Apr;38(4):126-30.

12. Nutrients. 2015 Sep 15;7(9):7798-805.

13. Allergy. 2014 Oct;69(10):1405-11.

14. Yakugaku Zasshi. 2014;134(1):33-8.

15. Intern Med. 2014;53(2):151-4.

16. Dermatitis. 2012 Sep-Oct;23(5):220-1.

17. Acta Medica (Hradec Kralove). 2011;54(4):157-62.

18. Contact Dermatitis. 2006 May;54(5):283-9.

19. Contact Dermatitis. 2013 Jun;68(6):379-80.

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

Gluten-free food products have inundated the marketplace in recent years as the food industry has responded to greater awareness of celiac sprue disease and wheat sensitivity. Gluten is the primary form of wheat protein.

Wheat is a versatile and globally popular member of the Poaceae or Gramineae family known as grasses; it is of the Triticum species with Triticum aestivum and Triticum vulgare being particularly pervasive.¹ In traditional Iranian medicine, the topical application of wheat germ oil has been used to treat psoriasis.²

Moisturization

In 2008, N. Akhtar and Y. Yazan investigated the effects of a stable emulsion containing two ingredients included to exert anti-aging effects: vitamin C and wheat protein. The antioxidant vitamin C was entrapped in the inner aqueous phase of the water-in-oil-in-water emulsion while wheat protein was incorporated in the oily phase. The investigators prepared and applied stable emulsions to the cheeks of 11 volunteers over 4 weeks, finding that the formulation increased skin moisture.⁷

Melanoma and wheat supplementation

Demidov et al. reported in 2008 on a randomized, pilot, phase II clinical trial to assess the impact of the adjuvant use of a fermented wheat germ extract nutraceutical (Avemar) in high-risk cutaneous melanoma patients. Investigators compared the efficacy of dacarbazine-based adjuvant chemotherapy on survival parameters of melanoma patients to that of the identical treatment supplemented with a 1-year administration of fermented wheat germ extract nutraceutical (FWGE), which is generally recognized as safe. They reported that after a 7-year follow-up, significant differences favoring the nutraceutical group were observed in progression-free and overall survival. Including nutraceutical as an adjuvant treatment for such patients was recommended by the authors.⁸

Telekes et al. noted that nutraceutical is registered as a special nutriment for cancer patients in Hungary that has exhibited potent anticancer activity on cell lines and immunomodulatory activity in vivo.⁹ In 2005, Boros et al. reported that orally administered FWGE suppressed metastatic tumor dissemination and proliferation during and after chemotherapy, surgery, or radiation, with benefits seen in some human cancers and cultured cells as well as some autoimmune disorders and in chemical carcinogenesis prevention.¹⁰

Hypersensitivity and allergic reactions

The risks of sensitization to topical wheat proteins are thought to be higher in patients with atopic dermatitis, who have an impaired skin barrier.¹ Indeed, Codreanu et al. have suggested that topical products containing food proteins of known allergenicity (including wheat) are contraindicated for neonates and infants with atopic dermatitis.¹¹

In 2015, Bonciolini et al. studied 17 patients (13 females and 4 males, median age 36 years) with nonceliac gluten sensitivity presenting with nonspecific skin lesions. The eczema-, psoriasis-, or dermatitis herpetiformis-like lesions on the extensor surfaces of the upper and lower limbs, especially, were confirmed histologically, but immunopathological evaluations revealed pervasive C3 deposits along the dermoepidermal junction in a microgranular/granular pattern (82%). Notably, all of the patients improved markedly after initiating a gluten-free diet.¹²

In 2014, Fukutomi et al. conducted a case-control study of Japanese women aged 20-54 years (157 cases) who self-reported wheat allergy to ascertain the epidemiologic relationship between food allergy to wheat after exposure to facial soaps containing hydrolyzed wheat protein. There were 449 age-matched controls without wheat allergy. Participants answered a Web-based questionnaire about their use of skin and hair care products. The investigators found that current use of the facial soap Cha no Shizuku (Drop of Tea), which contains hydrolyzed wheat protein, was significantly linked to a greater risk of wheat allergy, with use of the soap more frequent in consumers whose wheat allergy had newly emerged (11% vs. 6% in controls).¹³

Cha no Shizuku had earlier been implicated in provoking hundreds of cases of allergic reactions between 2009 and June 2013. R. Teshima noted that the soap contains acid-hydrolyzed wheat protein produced from gluten after partial hydrolysis with hydrogen chloride at 95 ° C for 40 minutes.¹⁴

It is worth noting that case reports of allergic reactions to facial soap containing hydrolyzed wheat protein continue to appear. Iseki et al. described in 2014 a 38-year-old woman who experienced irregular headaches, sleepiness, and an episode of facial rash eruption after daily use for about 1 year of a facial soap with hydrolyzed wheat proteins (Glupearl 19s, which is also used in Cha no Shizuku). The investigators added that the patient’s serum contained wheat-specific IgE antibodies. Symptoms disappeared after the patient abstained from wheat.¹⁵

In 2012, Tammaro studied cutaneous hypersensitivity to gluten in 14 female patients (aged 12-60 years) with celiac disease who presented with eczema on the face, neck, and arms, after topical application of gluten-containing emollient cream, bath or face powder, or contact with foods containing wheat and durum. Five of the patients tested positive for wheat and durum wheat, while none of the 14 control patients tested positive. Improvement in cutaneous lesions, with no relapses during a 6-month follow-up, resulted when these patients used gluten-free cream and bath powder, and wore gloves before handling wheat-containing food.¹⁶

In 2011, Celakovská et al. studied the impact of wheat allergy in 179 adults with atopic eczema (128 females, 51 males; average age 26 years), using open exposure and double-blind, placebo-controlled food challenge tests, as well as specific serum IgE, skin prick, and atopy patch tests. The double-blind, placebo-controlled food challenge test showed that the course of atopic eczema was exacerbated by wheat allergy in eight patients (4.5%). A positive trend revealing that the course of atopic eczema was impacted by wheat allergy emerged during follow-up (at 3, 6, 9, and 12 months).¹⁷

Contact urticaria also has been reported to have been induced by hydrolyzed wheat proteins in cosmetics and is notable for the potential to precede food allergies.^2,3 A wide variety of protein hydrolysates found in hair products have been associated with inducing contact urticaria, particularly in patients with atopic dermatitis.⁴

In 2006, Laurière et al. studied nine female patients without common wheat allergy who presented with contact urticaria to cosmetics containing hydrolyzed wheat proteins; six also had experienced generalized urticaria or anaphylaxis in response to foods containing such wheat proteins. Analyses revealed the importance of hydrolysis in augmenting the allergenicity of wheat proteins through contact or consumption.¹⁸ Immediate contact urticaria in reaction to hydrolyzed wheat protein in topical products also has been reported in a child.¹⁹

Conclusion

Can the presence of wheat hydrolysates in personal care products adversely affect a patient with celiac sprue or wheat sensitivity? The short answer appears to be “yes.” Given the use of hydrolyzed wheat protein in various skin care products, it is important that consumers who have celiac disease or sensitivity to wheat be advised to avoid skin care formulations with such active ingredients. On the positive side of the wheat ledger, there are some indications (albeit in very limited research) that the plant protein may impart beneficial health effects. Much more research is necessary to delineate the full impact of wheat on skin health.

I thank my dermatologist colleague Sharon E. Jacob, MD, at the University of Miami, for suggesting this topic.

References

1. Dermatitis. 2013 Nov-Dec;24(6):291-5.

2. Iran J Med Sci. 2016 May;41(3 Suppl):S54.

3. Contact Dermatitis. 2007 Feb;56(2):119-20.

4. Ann Dermatol Venereol. 2010 Apr;137(4):281-4.

5. Allergy. 1998 Nov;53(11):1078-82.

6. J Drugs Dermatol. 2013 Sep;12(9 Suppl):s133-6.

7. Pak J Pharm Sci. 2008 Jan;21(1):45-50.

8. Cancer Biother Radiopharm. 2008 Aug;23(4):477-82.

9. Nutr Cancer. 2009;61(6):891-9.

10. Ann N Y Acad Sci. 2005 Jun;1051:529-42.

11. Eur Ann Allergy Clin Immunol. 2006 Apr;38(4):126-30.

12. Nutrients. 2015 Sep 15;7(9):7798-805.

13. Allergy. 2014 Oct;69(10):1405-11.

14. Yakugaku Zasshi. 2014;134(1):33-8.

15. Intern Med. 2014;53(2):151-4.

16. Dermatitis. 2012 Sep-Oct;23(5):220-1.

17. Acta Medica (Hradec Kralove). 2011;54(4):157-62.

18. Contact Dermatitis. 2006 May;54(5):283-9.

19. Contact Dermatitis. 2013 Jun;68(6):379-80.

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

Silver is a naturally occurring chemical element (number 47 on the periodic table) with the chemical symbol Ag, which is derived from the Latin word argentum (árgyros in Greek), from the Indo-European root “arg-,” meaning “shining,” “white,” or “gray.” It has been used for medical purposes since ancient times, with Hippocrates (circa 460-370 BCE) noting the beneficial healing and disease-altering activity of the element.¹

In modern times, silver compounds – in metallic, nanocrystalline, and ionic formulations – have exhibited broad antibacterial activity and attracted interest for topical antiseptic use in wound dressings.² Nanocrystalline silver dressings were introduced commercially as antimicrobial dressings in 1998.³ Silver is now used in dressings, catheters, cleansers, ophthalmic ointments, and myriad other medical products. In 2010 alone, an estimated 15 metric tons of silver were incorporated into medical products worldwide.⁴ It also is included in personal care products, textiles, and water purification devices. In topical skin preparations, the noble metal is included as colloidal silver (suspension of silver particles in an aqueous base) or nanosilver (as nanoparticles ranging from 1 nm to 100 nm in at least one dimension).⁵ Silver has been used to treat burns and wounds, but this discussion will be limited to acne, atopic dermatitis, and the anti-inflammatory response.

Anti-inflammatory uses

For several decades, noble metals including silver have been known to exert anti-inflammatory activity.^7-11 In the case of silver, its anti-inflammatory properties appear to be mediated by its influence on the cytokine system. Silver nanoparticles inhibit the activity of interleukin-6 (IL-6), IL-12, IL-1beta, and tumor necrosis factor–alpha (TNF-alpha). This impact on the cytokine system is responsible for the impact of silver in demonstrably alleviating symptoms of rheumatoid arthritis.³

In 2004, Bhol et al. used dinitrochlorobenzene (DNCB) to induce allergic contact dermatitis in a guinea pig model, finding that topical nanocrystalline silver cream dose-dependently decreased erythema and as effectively as topical steroids and immunosuppressants.¹² The next year, Bhol and Schechter showed that nanocrystalline silver suppressed allergic contact dermatitis in mice, inhibited TNF-alpha and IL-12 expression, and induced inflammatory cell apoptosis.¹³

In 2008, Nadworny et al. used a porcine contact dermatitis model to investigate the anti-inflammatory activity of nanocrystalline silver. They found that nanocrystalline silver treatments reduced DNCB-induced erythema and edema, promoted apoptosis in dermal cells, and diminished matrix metalloproteinase (MMP) and proinflammatory cytokine expression.³ The investigators speculated that the lower TNF-alpha observed in the silver-treated animals occurred due to apoptosis of the inflammatory cells.

Acne

Silver acts as a bactericidal and anti-inflammatory agent, without generating free radicals, as seen with benzoyl peroxide. Therefore, it is a compelling option for responding to the presence of Propionibacterium acnes. However, silver has not been approved by the Food and Drug Administration for this use. Even though formal acne studies have not been performed with silver sulfadiazine, it has long been used “off-label” for this purpose. As suggested above, the use of silver sulfadiazine for acne is limited by the risk of sulfa allergy. Cosmetic appearance and ease of use also are limiting factors, as silver sulfadiazine preparations are characterized by a thick, white pasty consistency. Other options for use of silver to treat acne include silver-containing cleansers and textiles.

Atopic dermatitis

A 2006 study in patients with atopic dermatitis demonstrated that silver-coated textiles could significantly diminish Staphylococcus aureus density after 2 days of wearing, with the effect enduring through the end of 7 days of treatment and then 1 week after removal of the textiles.¹⁴ Within 2 weeks, objective and subjective symptoms of atopic dermatitis were significantly enhanced in association with the silver-coated textiles, compared with cotton, without measurable adverse effects. A technology called Padycare incorporates silver into micromesh material (82% polyamide, 18% Lycra) used in clothing and bedding.¹⁵ As compared with topical formulations applied directly to the skin, textiles confer certain advantages such as preventing scratching and protecting against irritating substances and allergens. Washing of silver-infused textiles is a possible disadvantage, though, as the amount of silver lost from textiles can range from a 100% loss after four washings to less than a 1% loss.¹⁶ It also is important to note that there are concerns regarding the potential of silver to leak from textiles into the water supply, and eradicating the beneficial bacteria used to treat the water.

Conclusion

Despite centuries of medical use, silver has not been approved by the FDA for any medical applications. Further study, particularly in terms of safety and efficacy, is necessary. Nevertheless, it is used off-label before and after minimally invasive dermatologic procedures (for example, dermal filling, botulinum toxin injections, chemical peeling) because of its antimicrobial and anti-inflammatory activities as well as soothing qualities for facial skin and the skin barrier. Silver appears to be particularly suitable for use as an acne therapy option due to the low risk of bacterial resistance, lack of irritation, and its preservation of the skin barrier unlike harsher options such as retinoids, antibiotics, and benzoyl peroxide.

References

1. Adv Skin Wound Care. 2006 Nov-Dec;19(9):472-4.

2. Clin Infect Dis. 2009 Nov 15;49(10):1541-9.

3. Nanomedicine. 2008 Sep;4(3):241-51.

4. J Antimicrob Chemother. 2013 Jan;68(1):131-8.

5. Nanocrystalline Silver: Use in wound care, in Current Advances in the Medical Application of Nanotechnology (Manchester, England: Bentham Books, 2012, pp. 25-31).

6. Nanomedicine. 2013 Jan;9(1):39-54.

7. Jpn J Pharmacol. 1965 Jun;15(2):131-4.

8. J Allergy Clin Immunol. 1995 Aug;96(2):251-6.

9. Inflamm Res. 2003 Dec;52(12):487-501.

10. J Nutr Environ Med. 1997;7(4):295-305.

11. Clin Exp Pharmacol Physiol. 2000 Mar;27(3):139-44.

12. Clin Exp Dermatol. 2004 May;29(3):282-7.

13. Br J Dermatol. 2005 Jun;152(6):1235-42.

14. Curr Probl Dermatol. 2006;33:152-64.

15. J Eur Acad Dermatol Venereol. 2006 May;20(5):534-41.

16. Environ Sci Technol. 2008 Jun 1;42(11):4133-9.
 

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

Silver is a naturally occurring chemical element (number 47 on the periodic table) with the chemical symbol Ag, which is derived from the Latin word argentum (árgyros in Greek), from the Indo-European root “arg-,” meaning “shining,” “white,” or “gray.” It has been used for medical purposes since ancient times, with Hippocrates (circa 460-370 BCE) noting the beneficial healing and disease-altering activity of the element.¹

In modern times, silver compounds – in metallic, nanocrystalline, and ionic formulations – have exhibited broad antibacterial activity and attracted interest for topical antiseptic use in wound dressings.² Nanocrystalline silver dressings were introduced commercially as antimicrobial dressings in 1998.³ Silver is now used in dressings, catheters, cleansers, ophthalmic ointments, and myriad other medical products. In 2010 alone, an estimated 15 metric tons of silver were incorporated into medical products worldwide.⁴ It also is included in personal care products, textiles, and water purification devices. In topical skin preparations, the noble metal is included as colloidal silver (suspension of silver particles in an aqueous base) or nanosilver (as nanoparticles ranging from 1 nm to 100 nm in at least one dimension).⁵ Silver has been used to treat burns and wounds, but this discussion will be limited to acne, atopic dermatitis, and the anti-inflammatory response.

Anti-inflammatory uses

For several decades, noble metals including silver have been known to exert anti-inflammatory activity.^7-11 In the case of silver, its anti-inflammatory properties appear to be mediated by its influence on the cytokine system. Silver nanoparticles inhibit the activity of interleukin-6 (IL-6), IL-12, IL-1beta, and tumor necrosis factor–alpha (TNF-alpha). This impact on the cytokine system is responsible for the impact of silver in demonstrably alleviating symptoms of rheumatoid arthritis.³

In 2004, Bhol et al. used dinitrochlorobenzene (DNCB) to induce allergic contact dermatitis in a guinea pig model, finding that topical nanocrystalline silver cream dose-dependently decreased erythema and as effectively as topical steroids and immunosuppressants.¹² The next year, Bhol and Schechter showed that nanocrystalline silver suppressed allergic contact dermatitis in mice, inhibited TNF-alpha and IL-12 expression, and induced inflammatory cell apoptosis.¹³

In 2008, Nadworny et al. used a porcine contact dermatitis model to investigate the anti-inflammatory activity of nanocrystalline silver. They found that nanocrystalline silver treatments reduced DNCB-induced erythema and edema, promoted apoptosis in dermal cells, and diminished matrix metalloproteinase (MMP) and proinflammatory cytokine expression.³ The investigators speculated that the lower TNF-alpha observed in the silver-treated animals occurred due to apoptosis of the inflammatory cells.

Acne

Silver acts as a bactericidal and anti-inflammatory agent, without generating free radicals, as seen with benzoyl peroxide. Therefore, it is a compelling option for responding to the presence of Propionibacterium acnes. However, silver has not been approved by the Food and Drug Administration for this use. Even though formal acne studies have not been performed with silver sulfadiazine, it has long been used “off-label” for this purpose. As suggested above, the use of silver sulfadiazine for acne is limited by the risk of sulfa allergy. Cosmetic appearance and ease of use also are limiting factors, as silver sulfadiazine preparations are characterized by a thick, white pasty consistency. Other options for use of silver to treat acne include silver-containing cleansers and textiles.

Atopic dermatitis

A 2006 study in patients with atopic dermatitis demonstrated that silver-coated textiles could significantly diminish Staphylococcus aureus density after 2 days of wearing, with the effect enduring through the end of 7 days of treatment and then 1 week after removal of the textiles.¹⁴ Within 2 weeks, objective and subjective symptoms of atopic dermatitis were significantly enhanced in association with the silver-coated textiles, compared with cotton, without measurable adverse effects. A technology called Padycare incorporates silver into micromesh material (82% polyamide, 18% Lycra) used in clothing and bedding.¹⁵ As compared with topical formulations applied directly to the skin, textiles confer certain advantages such as preventing scratching and protecting against irritating substances and allergens. Washing of silver-infused textiles is a possible disadvantage, though, as the amount of silver lost from textiles can range from a 100% loss after four washings to less than a 1% loss.¹⁶ It also is important to note that there are concerns regarding the potential of silver to leak from textiles into the water supply, and eradicating the beneficial bacteria used to treat the water.

Conclusion

Despite centuries of medical use, silver has not been approved by the FDA for any medical applications. Further study, particularly in terms of safety and efficacy, is necessary. Nevertheless, it is used off-label before and after minimally invasive dermatologic procedures (for example, dermal filling, botulinum toxin injections, chemical peeling) because of its antimicrobial and anti-inflammatory activities as well as soothing qualities for facial skin and the skin barrier. Silver appears to be particularly suitable for use as an acne therapy option due to the low risk of bacterial resistance, lack of irritation, and its preservation of the skin barrier unlike harsher options such as retinoids, antibiotics, and benzoyl peroxide.

References

1. Adv Skin Wound Care. 2006 Nov-Dec;19(9):472-4.

2. Clin Infect Dis. 2009 Nov 15;49(10):1541-9.

3. Nanomedicine. 2008 Sep;4(3):241-51.

4. J Antimicrob Chemother. 2013 Jan;68(1):131-8.

5. Nanocrystalline Silver: Use in wound care, in Current Advances in the Medical Application of Nanotechnology (Manchester, England: Bentham Books, 2012, pp. 25-31).

6. Nanomedicine. 2013 Jan;9(1):39-54.

7. Jpn J Pharmacol. 1965 Jun;15(2):131-4.

8. J Allergy Clin Immunol. 1995 Aug;96(2):251-6.

9. Inflamm Res. 2003 Dec;52(12):487-501.

10. J Nutr Environ Med. 1997;7(4):295-305.

11. Clin Exp Pharmacol Physiol. 2000 Mar;27(3):139-44.

12. Clin Exp Dermatol. 2004 May;29(3):282-7.

13. Br J Dermatol. 2005 Jun;152(6):1235-42.

14. Curr Probl Dermatol. 2006;33:152-64.

15. J Eur Acad Dermatol Venereol. 2006 May;20(5):534-41.

16. Environ Sci Technol. 2008 Jun 1;42(11):4133-9.
 

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

Silver is a naturally occurring chemical element (number 47 on the periodic table) with the chemical symbol Ag, which is derived from the Latin word argentum (árgyros in Greek), from the Indo-European root “arg-,” meaning “shining,” “white,” or “gray.” It has been used for medical purposes since ancient times, with Hippocrates (circa 460-370 BCE) noting the beneficial healing and disease-altering activity of the element.¹

In modern times, silver compounds – in metallic, nanocrystalline, and ionic formulations – have exhibited broad antibacterial activity and attracted interest for topical antiseptic use in wound dressings.² Nanocrystalline silver dressings were introduced commercially as antimicrobial dressings in 1998.³ Silver is now used in dressings, catheters, cleansers, ophthalmic ointments, and myriad other medical products. In 2010 alone, an estimated 15 metric tons of silver were incorporated into medical products worldwide.⁴ It also is included in personal care products, textiles, and water purification devices. In topical skin preparations, the noble metal is included as colloidal silver (suspension of silver particles in an aqueous base) or nanosilver (as nanoparticles ranging from 1 nm to 100 nm in at least one dimension).⁵ Silver has been used to treat burns and wounds, but this discussion will be limited to acne, atopic dermatitis, and the anti-inflammatory response.

Anti-inflammatory uses

For several decades, noble metals including silver have been known to exert anti-inflammatory activity.^7-11 In the case of silver, its anti-inflammatory properties appear to be mediated by its influence on the cytokine system. Silver nanoparticles inhibit the activity of interleukin-6 (IL-6), IL-12, IL-1beta, and tumor necrosis factor–alpha (TNF-alpha). This impact on the cytokine system is responsible for the impact of silver in demonstrably alleviating symptoms of rheumatoid arthritis.³

In 2004, Bhol et al. used dinitrochlorobenzene (DNCB) to induce allergic contact dermatitis in a guinea pig model, finding that topical nanocrystalline silver cream dose-dependently decreased erythema and as effectively as topical steroids and immunosuppressants.¹² The next year, Bhol and Schechter showed that nanocrystalline silver suppressed allergic contact dermatitis in mice, inhibited TNF-alpha and IL-12 expression, and induced inflammatory cell apoptosis.¹³

In 2008, Nadworny et al. used a porcine contact dermatitis model to investigate the anti-inflammatory activity of nanocrystalline silver. They found that nanocrystalline silver treatments reduced DNCB-induced erythema and edema, promoted apoptosis in dermal cells, and diminished matrix metalloproteinase (MMP) and proinflammatory cytokine expression.³ The investigators speculated that the lower TNF-alpha observed in the silver-treated animals occurred due to apoptosis of the inflammatory cells.

Acne

Silver acts as a bactericidal and anti-inflammatory agent, without generating free radicals, as seen with benzoyl peroxide. Therefore, it is a compelling option for responding to the presence of Propionibacterium acnes. However, silver has not been approved by the Food and Drug Administration for this use. Even though formal acne studies have not been performed with silver sulfadiazine, it has long been used “off-label” for this purpose. As suggested above, the use of silver sulfadiazine for acne is limited by the risk of sulfa allergy. Cosmetic appearance and ease of use also are limiting factors, as silver sulfadiazine preparations are characterized by a thick, white pasty consistency. Other options for use of silver to treat acne include silver-containing cleansers and textiles.

Atopic dermatitis

A 2006 study in patients with atopic dermatitis demonstrated that silver-coated textiles could significantly diminish Staphylococcus aureus density after 2 days of wearing, with the effect enduring through the end of 7 days of treatment and then 1 week after removal of the textiles.¹⁴ Within 2 weeks, objective and subjective symptoms of atopic dermatitis were significantly enhanced in association with the silver-coated textiles, compared with cotton, without measurable adverse effects. A technology called Padycare incorporates silver into micromesh material (82% polyamide, 18% Lycra) used in clothing and bedding.¹⁵ As compared with topical formulations applied directly to the skin, textiles confer certain advantages such as preventing scratching and protecting against irritating substances and allergens. Washing of silver-infused textiles is a possible disadvantage, though, as the amount of silver lost from textiles can range from a 100% loss after four washings to less than a 1% loss.¹⁶ It also is important to note that there are concerns regarding the potential of silver to leak from textiles into the water supply, and eradicating the beneficial bacteria used to treat the water.

Conclusion

Despite centuries of medical use, silver has not been approved by the FDA for any medical applications. Further study, particularly in terms of safety and efficacy, is necessary. Nevertheless, it is used off-label before and after minimally invasive dermatologic procedures (for example, dermal filling, botulinum toxin injections, chemical peeling) because of its antimicrobial and anti-inflammatory activities as well as soothing qualities for facial skin and the skin barrier. Silver appears to be particularly suitable for use as an acne therapy option due to the low risk of bacterial resistance, lack of irritation, and its preservation of the skin barrier unlike harsher options such as retinoids, antibiotics, and benzoyl peroxide.

References

1. Adv Skin Wound Care. 2006 Nov-Dec;19(9):472-4.

2. Clin Infect Dis. 2009 Nov 15;49(10):1541-9.

3. Nanomedicine. 2008 Sep;4(3):241-51.

4. J Antimicrob Chemother. 2013 Jan;68(1):131-8.

5. Nanocrystalline Silver: Use in wound care, in Current Advances in the Medical Application of Nanotechnology (Manchester, England: Bentham Books, 2012, pp. 25-31).

6. Nanomedicine. 2013 Jan;9(1):39-54.

7. Jpn J Pharmacol. 1965 Jun;15(2):131-4.

8. J Allergy Clin Immunol. 1995 Aug;96(2):251-6.

9. Inflamm Res. 2003 Dec;52(12):487-501.

10. J Nutr Environ Med. 1997;7(4):295-305.

11. Clin Exp Pharmacol Physiol. 2000 Mar;27(3):139-44.

12. Clin Exp Dermatol. 2004 May;29(3):282-7.

13. Br J Dermatol. 2005 Jun;152(6):1235-42.

14. Curr Probl Dermatol. 2006;33:152-64.

15. J Eur Acad Dermatol Venereol. 2006 May;20(5):534-41.

16. Environ Sci Technol. 2008 Jun 1;42(11):4133-9.
 

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

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

Photoprotective activity

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

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

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

Antioxidant activity

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

Antimicrobial activity

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

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

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

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

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

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

Insect repellent activity

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

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

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

Melanoma

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

Conclusion

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

References

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Photoprotective activity

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

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

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

Antioxidant activity

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

Antimicrobial activity

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

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

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

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

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

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

Insect repellent activity

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

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

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

Melanoma

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

Conclusion

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

References

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Photoprotective activity

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

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

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

Antioxidant activity

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

Antimicrobial activity

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

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

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

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

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

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

Insect repellent activity

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

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

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

Melanoma

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

Conclusion

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

References

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Constituents

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

Anti-inflammatory effects

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

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

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

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

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

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

Conclusion

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

References

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

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

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

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

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

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

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

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

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

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

Constituents

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

Anti-inflammatory effects

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

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

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

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

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

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

Conclusion

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

References

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

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

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

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

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

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

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

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

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

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

Constituents

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

Anti-inflammatory effects

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

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

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

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

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

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

Conclusion

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

References

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

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

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

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

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

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

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

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

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

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

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

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

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

Chemistry

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

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

Topical uses

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

Conclusion

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Chemistry

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

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

Topical uses

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

Conclusion

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Chemistry

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

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

Topical uses

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

Conclusion

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Skin cancer and photoprotection

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

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

By Rj1979/ Wikimedia Commons/ public domain

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

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

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

Antiaging activity

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

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

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

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

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

Skin lightening

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

Acne

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

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

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

Erythema

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

Conclusion

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

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

References

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Skin cancer and photoprotection

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

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

By Rj1979/ Wikimedia Commons/ public domain

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

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

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

Antiaging activity

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

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

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

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

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

Skin lightening

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

Acne

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

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

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

Erythema

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

Conclusion

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

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

References

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Skin cancer and photoprotection

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

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

By Rj1979/ Wikimedia Commons/ public domain

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

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

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

Antiaging activity

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

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

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

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

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

Skin lightening

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

Acne

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

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

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

Erythema

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

Conclusion

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

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

References

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Topical uses and findings

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

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

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

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

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

The vitamin C, vitamin E, ferulic acid combination

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

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

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

Other vitamin E combinations

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

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

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

Conclusion

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

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

References

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Topical uses and findings

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

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

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

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

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

The vitamin C, vitamin E, ferulic acid combination

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

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

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

Other vitamin E combinations

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

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

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

Conclusion

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

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

References

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Topical uses and findings

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

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

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

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

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

The vitamin C, vitamin E, ferulic acid combination

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

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

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

Other vitamin E combinations

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

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

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

Conclusion

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

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

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