Treating Aging Skin |
Moisturizers |
Vitamin A Derivatives
Exfoliators |
Hormones |
Antioxidants
Neurotoxins |
Growth Factors |
Miscellaneous
Sunscreen |
The Bottom Line |
References
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The main reason skin looks older, wrinkled and rough, or speckled with dark spots isn't age itself. It's sun exposure.6064,12251,12252
Compare the skin on the outside of the arm with the skin on the underside. Which side looks younger? The outside, which gets sun exposure, shows far more signs of aging than the unexposed underside surface. This skin damage caused by the sun's ultraviolet (UV) radiation is called photoaging.6064,12251,12253,15382
Photoaging doesn't just cause wrinkles, dark spots, and a less youthful appearance.12251,12253 It can also lead to more serious conditions including rosacea and premalignant lesions such as actinic keratoses.12254,12255
The changes in the skin caused by sun exposure are a bit different than the changes that result from natural or chronological aging. Regardless of sun exposure, everyone gets expression lines, thin wrinkles, and sagging skin as they grow older...how much is largely determined by genetics.12251,12253
| Practice Pearl |
| Smoking makes skin look older, especially in the facial area. This might be due to direct adverse effects on skin fibroblasts.15382 Explain to smokers that this is another good reason for quitting. |
UV radiation from the sun causes erythema and reduces the number of dermal blood vessels that supply nutrients to the skin.12256 Sunlight damages collagen and elastin, which are important for maintaining skin tone.12256 UV radiation also generates oxidants and creates damaged keratinocytes called "sunburn cells."6155,12255
You'll often hear about different types of UV radiation. UVA rays are longer, penetrate deeper into the skin, and are thought to be most responsible for aging skin.6155,12253 UVB rays are thought to be more superficial and responsible for sunburn and tanning.
| Practice Pearl |
| You get both UVA and UVB radiation from sun exposure AND from tanning beds. Advise patients that tanning beds can cause the same skin damage and accelerate aging skin just like sun exposure. |
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Question #1 | | Photoaging | | | | | | | | |
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| | Treating Aging Skin |  | |
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Aging Baby Boomers are now creating a HUGE market for skin care products that they hope will "turn back time." There are a lot of new anti-aging products on the market. These products are often called "cosmeceuticals." They're promoted as being more powerful than regular cosmetics, but not so powerful that they're regulated like drugs. Many come in the form of facial creams or lotions, beefed up with antioxidants and other interesting ingredients. Some cosmeceuticals are even taken by mouth.
| *Note: Many natural products are tried for aging skin, but very few have reliable evidence that they work. Inclusion in this list does NOT imply that these products are effective for aging skin.
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| | | | Moisturizers | | |
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Products that introduce moisture into the skin or keep moisture from leaving the skin are called moisturizers or emollients. They are included in most products used for aging skin.
Occlusive products are the most common moisturizers. They are typically oily or waxy substances that form a layer over the skin and therefore prevent moisture from leaving the skin. Some of these include jojoba (Simmondsia chinensis), avocado oil (Persea americana), emu oil (Dromiceius novahollandiae), shea butter, cocoa butter (Theobroma cacao), petrolatum, lanolin, or mineral oil.12262,12263
| Practice Pearl |
| Warn patients who are sensitive to latex that they might also be sensitive to avocado.6197,7853 |
Humectants are hydrating agents. They draw water from within the skin to the surface layer. When in a very humid environment, humectants can also pull water from the air into the skin. Humectants include glycerin, propylene glycol, hyaluronic acid, lecithin, and many others.
Most skin care products contain a combination of different types of moisturizers.
Explain to patients that dry skin doesn't cause wrinkles. But it can make wrinkles more pronounced. Using products containing these moisturizers can temporarily puff up the skin with water and reduce wrinkles. But moisturizers won't eliminate wrinkled skin altogether.
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| | | | Vitamin A Derivatives | | |
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The prescription vitamin A derivatives tretinoin (Retin-A, Renova) or tazarotene (Avage) are the gold-standard treatments for wrinkles.6064,12252 They cause structural changes in the skin by removing the top skin layers and forming new collagen and blood vessels.6062,6064,12257 This improves the overall appearance of skin by reducing wrinkles, dark spots, pore size, and improving skin tone and smoothness.6062,6064,12019,12252,12258 The downside is that the benefits of these drugs are short-lived. Once they are discontinued, the skin will gradually return to the way it was before the drug was started.6062,12257,12258 Safety can also be a concern. Some investigators worry that people who use one of these retinoids might have an increased risk of skin cancer if they get excessive exposure to sunlight or sunlamps.12257
Oral vitamin A supplements are also used. Vitamin A is contained in all kinds of cosmetic products. Some people think that because tretinoin is a vitamin A derivative, that vitamin A itself might also work. Vitamin A also has antioxidant effects that could potentially be helpful. But there is no reliable evidence that taking vitamin A orally or applying it topically can reduce wrinkles.
Caution people not to take high doses of vitamin A orally. Vitamin A is fat-soluble and accumulation can occur, causing toxicity. Most multivitamins contain less than 5000 units. Tell people not to take over 10,000 units/day of vitamin A.6062,12257
Beta-carotene is another vitamin A relative that is commonly used in skin care products.139,1470,6062 Beta-carotene is thought to work as an antioxidant and protect cells from oxidative damage due to UV radiation.139,6062 There is some evidence that taking beta-carotene supplements can reduce the severity of erythema in people with sun sensitivity.6134,11792 But beta-carotene doesn't seem to be helpful for most people with normal sensitivity to the sun.11792 And there is no reliable evidence that beta-carotene can reduce wrinkles or other signs of photoaged skin.
Warn patients that doses greater than 30 mg daily for prolonged periods can cause a yellow or orange discoloration of the skin.6062,12257
| Practice Pearl |
| Don't recommend beta-carotene for people who smoke. Taking doses of 20 mg or higher have been linked with an increased risk of lung and prostate cancer in people who smoke. |
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Question #2 | | Topical prescription vitamin A derivative products for treating aged skin | | | | | | | | |
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| | Exfoliators | | |
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Another approach to smoothing over wrinkles is to peel back layers of the skin...like an onion...to expose the fresh, younger looking skin below.
Sugar or salt scrubs take a physical approach to removing skin...by physical abrasion. These products contain mostly sugar or salt (often sea salt) in an oil base. The gritty scrub works a little like sandpaper. It's applied to the skin in a circular motion and physically removes the dead skin at the surface. And the oily base leaves behind a protective moisturizing layer.
Other than anecdotal success stories, there is no hard evidence that shows that these abrasive scrubs are effective for reducing wrinkles.
Alpha-hydroxy acids are a common ingredient in scrubs, lotions, and creams used for wrinkles. They are also used as a component of "chemical peels" applied to the face to peel off layers of skin.
Alpha-hydroxy acids are natural fruit acids including glycolic, lactic, and citric acids.6064 The most commonly used alpha-hydroxy acids are glycolic and lactic acids.6080
You can think of alpha-hydroxy acids in three groups, based on concentration. High concentrations of 50% to 70% are only for use in a physician's office. Only trained cosmetologists use medium concentrations of 20% to 30% for light peeling. Low concentrations of less than 10% are available to the consumer in a variety of cosmetic products.6064,6080
Most patients use the lower concentration alpha-hydroxy acids in cosmetic creams, lotions, and solutions. These products seem to be moderately effective for improving the signs of aging skin, including reducing wrinkles.952,953,954,8011 They are generally safe and well-tolerated when used short-term and appropriately.947,949,952,6080
| Practice Pearl |
| Tell patients using alpha-hydroxy acids to make sure they get protection from sun exposure. Alpha-hydroxy acids seem to increase people's sensitivity to the sun and might INCREASE skin damage. People using alpha-hydroxy acids should always use sunscreen of SPF 15 or greater. They should also wear wide-brimmed hats and cover-up clothing on their arms and legs. |
Sugarcane extract is also commonly listed as an ingredient in cosmetics promoted for wrinkles. These ingredients are often claimed to be the same or similar to alpha-hydroxy acids. But they are not. Glycolic acid, an alpha-hydroxy acid, can be produced from sugarcane. But purified glycolic acid is a lot different than a raw sugarcane extract. There is no reliable evidence that sugarcane extract works for wrinkles.
Other ingredients such as fruit extracts or mixed fruit extracts also claim to be like alpha-hydroxy acids. Like the sugarcane extract, there is no reliable evidence that these are effective.
Salicylic acid is very similar in chemical structure to alpha-hydroxy acids. It's often called a beta-hydroxy acid, but this classification is incorrect.12018
Salicylic acid is used for a variety of dermatologic conditions, including psoriasis and acne. Now it's becoming more common as a cosmetic ingredient.6064,12257 Salicylic acid seems to work by exfoliating the skin. Some practitioners think it can produce effects similar to alpha-hydroxy acids and might be less irritating than alpha-hydroxy acid products.6064 But so far, this hasn't been verified by clinical studies.
Pyruvic acid is an alpha-keto acid. It's similar to alpha-hydroxy acids. In fact, it's converted to the alpha-hydroxy acid, lactic acid. Some researchers are hoping that pyruvic acid will turn out to be as effective as the alpha-hydroxy acids, but with less irritation. So far there is preliminary evidence that a 50% pyruvic acid chemical peel can smooth skin and decrease wrinkles.12020 But this high concentration is only suitable for application in a physician's office.
Lower concentrations are available in cosmetics that are available to consumers. But it's not known if these lower concentrations are effective.
Papain (Carica papaya) is a natural proteolytic enzyme contained in papaya (Carica papaya). Papain is thought to help slough off dead skin cells and have an exfoliating effect. Both papain and papaya are common ingredients in products promoted for wrinkles. But neither ingredient has been shown to work.
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Question #3 | | Which statement about alpha-hydroxy acids is TRUE? | | | | | | | | |
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Question #4 | | Before heading off to the beach, a patient tells you she no longer is worried about sun exposure because she has a "cure" for wrinkles. She is using alpha-hydroxy acids and tretinoin. You can accurately tell her: | | | | | | | | |
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Question #5 | | Exfoliators work by peeling back the top layers of the skin like an onion and exposing new, younger looking cells. Which of the following works as an exfoliator? | | | | | | | | |
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| | Hormones | | |
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DHEA is a popular anti-aging supplement. But it's really more like a drug than a supplement. DHEA is a powerful hormone that gets converted in the body to both testosterone and estrogen. So it's no wonder that DHEA can improve the appearance of aging skin. It seems to increase skin thickness, improve skin hydration, and decrease facial skin pigmentation.6446
The downside is that DHEA can also have hormonal side effects...acne, hair loss, insulin resistance, menstrual changes, liver dysfunction, high blood pressure, etc.
Tell patients that the potential risks associated with DHEA outweigh the potential benefits for improving skin appearance.
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| | | | View brands containing: | | - | DHEA |
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| | Antioxidants | | |
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A popular approach to aging skin is to use antioxidants to prevent the oxidative damage caused by sun exposure and UV radiation.
Vitamin C is one of the most common antioxidants included in skin care products.12257 In addition to its antioxidant effects, vitamin C is thought to play a role in collagen synthesis and tissue repair.6062,6155 But vitamin C is water-soluble and therefore, taking it orally might not produce high enough concentrations in the skin to be beneficial.
There is preliminary evidence that shows a TOPICAL vitamin C formulation might help. Cellex-C High-Potency Serum combines 10% vitamin C with tyrosine, zinc, and hyaluronic acid. This specific product seems to reduce fine lines, wrinkles and roughness, and improve skin tone.6155,6166,12261
Additional preliminary evidence shows that a 3% vitamin C topical preparation applied for 12 weeks might also reduce facial wrinkles.14008
Lots of skin products contain vitamin C, but it might not be obvious after a first glance at the ingredient list. Some products list acerola (Malpighia glabra) or rose hips (Rosa canina). But these are just plant materials that contain a high concentration of vitamin C. There is no reliable evidence that these products are any better than regular vitamin C products.
Vitamin E is also a very popular antioxidant in skin care products. It's used both orally AND topically. It's thought to improve skin moisture, softness and smoothness, and provide mild protection from ultraviolet sun damage.6062,12261 But so far, there is no reliable clinical evidence that oral or topical vitamin E is helpful for improving signs of aging skin.
Interestingly, taking a combination of both vitamin C and vitamin E supplements ORALLY might help for prevention of photoaging. Taking 2 grams of vitamin C along with 1000 IU oral vitamin E before sun exposure, seems to reduce skin inflammation after sun exposure.4715,4716 But caution patients that these high doses might cause adverse effects in some people...nausea, vomiting, and diarrhea.
Applying a combination of vitamin C, vitamin E, and melatonin in a TOPICAL formulation also seems to provide a modest protective effect when used BEFORE sun exposure. It has no effect when applied during or after sun exposure.4713,4714
Alpha-lipoic acid is a potent antioxidant. It's best known for its use in diabetes patients. But researchers are now investigating the effectiveness of alpha-lipoic acid applied topically for aging skin. There is preliminary evidence that applying a 5% alpha-lipoic acid cream daily for 12 weeks can improve signs of aging skin such as wrinkles and roughness.12021
Green tea has become a very popular "healthy" drink. Now a lot of new cosmeceuticals are coming out with green tea extract as an ingredient. It's produced from the leaves and stems of the Camellia sinensis plant...the same plant used for black tea.12265 But green tea doesn't use fermented leaves like black tea.
Green tea is included in these new skin care products because it contains polyphenols that have antioxidant activity.4212 There are a lot of preliminary animal studies that show both topical and oral use might help prevent skin damage from sun exposure. But so far, there is no evidence in humans that it's effective for preventing aged skin or reducing the signs of existing wrinkles.6065
SunPill by Pure Pharmaceuticals is a popular brand name combination product that claims to be "specifically designed for sun protection." It contains a green tea extract along with a long list of other ingredients including vitamin C, vitamin E, vitamin D, Vitamin A, calcium, and others. There is no reliable scientific evidence that this particular combination works.15383 And there are concerns about safety. Each SunPill contains 12,500 units of vitamin A...which exceeds the tolerable upper intake level of 10,000 units per day. Advise patients to avoid this product.
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Question #6 | | People use the following agents topically to help prevent signs of aging skin. Which one has some scientific support of effectiveness? | | | | | | | | |
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| | Neurotoxins | | |
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Some people are also trying Botox (botulinum toxin) injections to reverse the deepened facial expression lines often associated with natural aging...frown lines, forehead lines, and crow's feet.12251,12254 Botulinum toxin is a neurotoxin produced by Clostridium botulinum.12253 It works by inhibiting the release of acetylcholine from motor nerve terminals12259 and temporarily paralyzing the muscles involved in wrinkle formation. The downside is that paralysis only lasts 3-4 months and extended treatment is necessary to maintain appearance. Although side effects are generally rare and mild, there isn't much information about the safety of prolonged use.12251,12259
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| | | | Growth Factors | | |
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Kinetin is a naturally occurring growth hormone found in plants. The idea is that this plant growth hormone might stimulate formation of younger looking skin.12022 A topical formulation called Kinerase is being promoted to reduce wrinkles. But there is no reliable evidence that it's effective for reducing wrinkles.
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| | | | Miscellaneous | | |
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Aloe gel is often applied topically for many skin conditions including wrinkled, aging skin. It's thought to have anti-inflammatory effects and help in wound healing. But there is no reliable evidence that it decreases wrinkles.
DMAE (Deanol or Dimethylaminoethanol) is ingredient that's becoming more popular in skin care products. It's already a popular supplement used for anti-aging. When taken ORALLY it increases acetylcholine levels. Therefore, it might improve memory. When applied topically some researchers think that DMAE might increase acetylcholine in the skin. This could affect smooth muscle contraction and potentially have a skin firming effect. There is preliminary evidence that applying a 3% DMAE gel might have a firming effect on loose skin.12023 But this is too preliminary to say just how effective DMAE products are.
DMAE is showing up in all kinds of facial moisturizers promoted to firm up sagging facial skin...DMAE Firming Fluid, DMAE Face Firming Serum, Anti-Wrinkle Firming Cream, etc. Since a one ounce bottle can cost upwards of $50, people might want to think twice before using them.
Polypodium leucotomos is a fern from Central America which contains phenolic compounds with antioxidant activity.14480 This plant is the main ingredient in a supplement product called Heliocare by Cantabria Farmaceutica. It's promoted to provide UV protection in a capsule. There is preliminary evidence that it can decrease redness and possibly reduce epidermal damage when taken orally before sun exposure.14365,15383
A topical lotion containing Polypodium leucotomos called Difur might also reduce photodamage when applied before sun exposure.14476
This evidence looks promising, but is very preliminary. Advise patients that these products shouldn't be substituted for using a sunscreen.
StriVectin-SD is a brand name combination product being marketed as "Better than Botox." StriVectin-SD contains a peptide called palmitoyl oligopeptide that the manufacturer claims can decrease wrinkles. It also contains over 20 other ingredients. Although it probably does help moisturize the skin, there is no reliable evidence that it reduces wrinkles...or that it works as well as Botox.
Lots of other natural products are being investigated and included in cosmetics used for aging skin...coenzyme Q-10, acetyl-L-carnitine, resveratrol, grape seed extract, and many others. But so far there is no proof that these can reduce wrinkles when applied to human skin or taken orally.
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Question #7 | | Which product is correctly matched with its pharmacological classification? | | | | | | | | |
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| | Sunscreen | | |
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The best offense against aging skin is a good defense against sun damage.
Sunscreen is the most effective skin defense on the market.12252,15382 Patients should use broad-spectrum sunscreens containing ingredients that protect against UVA rays...avobenzone, zinc oxide, and titanium dioxide. The use of a broad-spectrum sunscreen reduces damage to elastic tissue. More importantly, these sunscreens can help prevent melanoma and other types of skin cancer.12252 Recommend at least an SPF 15 sunscreen for most people, and 30+ for people who are more sensitive to the sun. Tell patients that protective clothing and a wide-brimmed hat of at least four inches can also help protect against the sun.12264 They can also try to stay out of the sun when the rays are strongest, usually between 10 am and 4 pm.12264 The bottom line...patients can best prevent premature aging of their skin by staying out of the sun when they can...and by using sunscreen when they can't.12256
Some people might ask you about a sunscreen called “mexoryl.” It wasn’t available in the United States until 2006. It’s in a sunscreen called Anthelios SX by L’Oreal. It specifically blocks UVA rays, which is thought to help reduce wrinkles.15384 For more information on this and other sunscreens, get the Pharmacist's Letter / Prescriber's Letter article on mexoryl and other sunscreens.
It's important to note that "waterproof" or "water-resistant" means that the SPF is maintained during 80 minutes of moderate activity or 40 minutes of swimming. The effectiveness of a sunscreen depends in part on the amount applied and environmental factors such as season, latitude, altitude, and reflection of UV rays off substances like sand, water, or snow. How quickly the sunscreen evaporates is also a consideration. Testing of sunscreens is normally done indoors, so when the above factors are considered, the actual protection can be considerably less than indicated by the SPF on the label. Advise patients to apply sunscreen liberally and to reapply sunscreen every two hours and after sweating, swimming, or toweling off.12255
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Question #8 | | Prevention is the best medicine. What's the best advice for someone who wants to minimize wrinkled skin? | | | | | | | | |
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| | The Bottom Line | | |
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Currently, the only approved prescription product for treating aged skin is tretinoin (Renova, Retin-A) and tazarotene (Avage). Topical alpha-hydroxy acids are also very commonly used and moderately effective.
Some natural products show promise...vitamin C and E together, alpha-lipoic acid, and DMAE. But it's too soon to recommend these products as reliable preventive measures or treatments of aging skin.
Patients can spend a LOT of extra money for products that boast natural ingredients with all sorts of exciting names and scientific sounding benefits. For now, tell them to save their money until the effects of these ingredients are better understood. Also, explain that more expensive skin care products aren't necessarily more effective. Many cheaper products contain the same ingredients as more expensive brand name products.
Emphasize to patients that prevention is the best medicine. Since sun exposure causes most of the undesirable effects on the skin, patients should always use sunscreen or cover exposed skin.
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Recommendation Chart for Natural Medicines Used for Aging Skin *
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| | KEY: | | Consider recommending this product.
| | | | | | Don't recommend using this product.
| | | | | | Recommend against using this product.
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* These proposed recommendations are based solely on the Safety and Effectiveness
Ratings contained in Natural Medicines Comprehensive Database. This assumes use
of high-quality, uncontaminated products and the use of typical doses. Keep in
mind that some products are never appropriate for some patients due to
concomitant disease states, potential drug interactions, or other clinical
factors. Use your clinical judgment before recommending any product.
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| References
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| | 139 | Omenn GS. Chemoprevention of lung cancer: the rise and demise of beta-carotene. Annu Rev Public Health 1998;19:73-99. | | 947 | Hunt MJ, Barnetson R. A comparative study of gluconolactone versus benzoyl peroxide in the treatment of acne. Australas J Dermatol 1992;33:131-4. | | 949 | Kempers S, Katz HI, Wildnauer R, Green B. An evaluation of the effect of an alpha hydroxy acid-blend skin cream in the cosmetic improvement of symptoms of moderate to severe xerosis, epidermolytic hyperkeratosis, and ichthyosis. Cutis 1998;61:347-50. | | 952 | Stiller MJ, Bartolone J, Stern R, et al. Topical 8% glycolic acid and 8% L-lactic acid creams for the treatment of photodamaged skin. A double-blind, vehicle-controlled clinical trial. Arch Dermatol 1996;132:631-6. | | 953 | Piacquadio D, Dobry M, Hunt S, et al. Short contact 70% glycolic acid peels as a treatment for photodamaged skin. A pilot study. Dermatol Surg 1996;22:449-52. | | 954 | Ditre CM, Griffin TD, Murphy GF, et al. Effects of alpha-hydroxy acids on photoaged skin: a pilot clinical, histologic, and ultrastructural study [see comments]. J Am Acad Dermatol 1996;34:187-95. | | 1470 | Cooper DA, Eldridge AL, Peters JC. Dietary carotenoids and certain cancers, heart disease, and age-related macular degeneration: a review of recent research. Nutr Rev 1999;57:201-14. | | 4212 | Klaunig JE, Xu Y, Han C, et al. The effect of tea consumption on oxidative stress in smokers and nonsmokers. Proc Soc Exp Biol Med 1999;220:249-54. | | 4713 | Dreher F, Gabard B, Schwindt DA, Maibach HI. Topical melatonin in combination with vitamins E and C protects skin from ultraviolet-induced erythema: a human study in vivo. Br J Dermatol 1998;139:332-9. | | 4714 | Dreher F, Denig N, Gabard B, et al. Effect of topical antioxidants on UV-induced erythema formation when administered after exposure. Dermatol 1999;198:52-5. | | 4715 | Fuchs J, Kern H. Modulation of UV-light-induced skin inflammation by D-alpha-tocopherol and L-ascorbic acid: a clinical study using solar simulated radiation. Free Radic Biol Med 1998;25:1006-12. | | 4716 | Eberlein-Konig B, Placzek M, Przybilla B. Protective effect against sunburn of combined systemic ascorbic acid (vitamin C) and d-alpha-tocopherol (vitamin E). J Am Acad Dermatol 1998;38:45-8. | | 6062 | Keller KL, Fenske NA. Uses of vitamins A, C, and E and related compounds in dermatology: A review. J Am Acad Dermatol 1998;39:611-25. | | 6064 | Kligman AM. Topical treatments for photoaged skin. Separating the reality from the hype. Postgrad Med 1997;102:115-26. | | 6065 | Katiyar SK, Ahmad N, Mukhtar H. Green Tea and Skin. Arch Dermatol 2000;136:989-94. | | 6080 | Kurtzweil P. Alpha-hydroxy acids for skin care: Smooth sailing or rough seas? FDA 1999. Available at: /www.fda.gov/fdac/features/1998/298_ahas.html (Accessed 18 August 2000). | | 6134 | Stahl W, Heinrich U, Jungmann H, et al. 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Cross-reactions in the latex-fruit syndrome: A relevant role of chitinases but not of complex asparagine-linked glycans. J Allergy Clin Immunol 1999;104:681-7. | | 8011 | Smith WP. Epidermal and dermal effects of topical lactic acid. J Am Acad Dermatol 1996;35:388-91. | | 11792 | Biesalski HK, Obermueller-Jevic UC. UV light, beta-carotene and human skin--beneficial and potentially harmful effects. Arch Biochem Biophys 2001;389:1-6. | | 12018 | Yu RJ, Van Scott EJ. Hydroxycarboxylic Acids, N-Acetylamino Sugars, and N-Acetylamino Acids. SKINmed 2002;2:117-22. | | 12019 | Phillips TJ, Gottlieb AB, Leyden JJ, et al. Efficacy of 0.1% tazarotene cream for the treatment of photodamage: A 12-month multicenter, randomized trail. Arch Dermatol 2002;138:1486-93. | | 12020 | Gheresitich I, Brazzini B, Perris K, et al. Pyruvic acid peels for the treatment of photoaging. Dermatol Surg 2004;30:32-6. | | 12021 | Beitner H. Randomized, placebo controlled, double-blind study on the clinical efficacy of a cream containing 5% alpha-lipoic acid related to photoaging of facial skin. Br J Dermatol 2003;149:841-9. | | 12022 | Rattan SI, Clark BF. Kinetin delays onset of aging characteristics in human fibroblasts. Biochem Biophys Res Commun 1994;201:665-72. | | 12023 | Uhoda I, Faska N, Robert C, et al. Split face study on the cutaneous tensile effect of 2-dimethylaminoethanol (deanol) gel. Skin Res Technol 2002;8:164-7. | | 12251 | Stratigos AJ, Arndt KA, Dover JS. Advances in cutaneous aesthetic surgery. JAMA 1998;280:1397-98. | | 12252 | Anon. Dermatologists can help consumers find the best products to rejuvenate their skin. American Academy of Dermatology, 1999. Available at: http://www.aad.org/PressReleases/rejuvenate.html | | 12253 | Anon. Skin trauma: A tan is an early warning sign. American Academy of Dermatology, 1996. 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