Ingredients for skin care: a new layer in anti-ageing
December 31, 2002
Just because a supplement works in an oral dose doesn't mean it will necessarily work topically. Dermal remedies applied topically need certain properties, such as the ability to permeate the epidermis, in order to produce benefits in the skin's inner dermis living cells. But because the skin's primary function is to protect the body from external pathogens, it poses a penetration challenge for some ingredients.
On the other hand, a compound that penetrates the skin entirely and reaches the blood stream may be considered a trans-dermal delivery system and could be regulated as a drug.
Optimally, a topical ingredient should penetrate the entire epidermis/dermis if it is to provide benefits. Using oil-based ingredients, or adding an oil or penetration agent to the product, can help the compounds get through the epidermis.
Good-looking ingredients
The primary causes of skin damage and ageing are exposure to sunlight—UVB and UVA—oxidation and inflammation of the skin, decreases in supportive collagen, loss of muscle tone, and dryness. Topical anti-ageing ingredients seek to ameliorate these conditions. Many supplements and herbs are potential skin remedies based on their demonstrated internal antioxidant and anti-inflammatory properties, but few have solid research to date. Popular vitamins, such as C and E, are well-studied for topical benefits. Other compounds, such as DMAE and Co-Q10, are supported by emerging research. The following are some of the popular, scientifically backed inclusions for today's anti-ageing skin care products.
VITAMIN C is a water-soluble antioxidant that traps free radicals and blocks the formation of nitrosamines—molecules suspected to be carcinogens. 1 Vitamin C has been found, in vitro, to be an indispensable player in the formation of the connective tissue collagen. 2 Collagen is the supportive framework of the skin and is crucial to optimal skin tone. The collagen molecule is a rod-like, triple-helix formed by three protein chains. When linked together, multiple collagen molecules form a matrix with the tensile strength of steel. The natural decrease of collagen with age leads to the formation of wrinkles when troughs of skin sag through a weakened support framework.
French researchers determined through human studies that the topical application of vitamin C stimulates collagen biosynthesis.3 At the 2000 World Congress of the International Academy of Cosmetic Surgery, researchers presented a double-blind, placebo-controlled trial of 20 female subjects, aged 55 to 60, who received a 5 per cent vitamin C cream or placebo for six months. At the study's conclusion, researchers discovered that the vitamin C cream had significantly reduced wrinkles and had rearranged wrinkle lines from deeper ruts into shallow, random order, a sign of younger skin and a stronger collagen matrix. The mechanism of action, in part, was C's stimulation of enzyme activity in the skin that created cross-linkages in the helices of collagen molecules.4
The same researchers further tested vitamin C on post-menopausal women—previously thought to have severely limited skin-collagen-production capacity—and found that topical vitamin C significantly increased the production of collagen vs. placebo.5
UV rays deplete vitamin C by as much as 30 per cent under minimal exposure and up to 55 per cent in ozone-depleted environments, dermatologist Karen E Burke, MD, PhD, reported at the 2002 American Academy of Dermatology annual meeting. A recent review from the Department of Dermatology at the University of California, San Francisco, states that topical application of vitamin C prevents UV damage, both UVB-induced erythema formation (skin inflammation and redness from capillary dilation) and UVA-related oxidative damage.6
The photoprotective effects of vitamin C can be enhanced by using combinations of antioxidants. In a randomised, double-blind human study, researchers determined, by applying C, or combinations of C, melatonin and vitamin E, 30 minutes prior to ultraviolet irradiation of the skin, that C in combination with other antioxidants exhibited greater photoprotectivity against UV exposure than vitamin C alone.7
VITAMIN E, probably the reigning antioxidant of our time and used to support everything from cancer therapy to cholesterol reduction and improved cardiac function, is also good for the skin.
The term vitamin E is the common description of one form of the vitamin, d-alpha-tocopherol, which is the natural form and is more active and better absorbed than a synthetic variety (referred to as dl-alpha-tocopherol), which is, however, less costly to produce and thus is more commonly used. Vitamin E in its entirety includes tocopherols and tocotrienols, each with four possible isomers for a total of eight varieties. Both tocopherols and tocotrienols are viable skin product ingredients, though tocopherols are most available and most widely used.
Tocotrienols, extracted from palm fruit, are considered more potent antioxidants.8 Research also suggests that tocotrienols are more biologically acceptable and are preferentially absorbed by the body and skin, based on their chemical structure.9 Studies show that topical tocotrienols prevent oxidation of the skin's collagen matrix.10
Burke reported that supplementing orally with 400mg vitamin E daily can reduce photodamage and wrinkles and can improve skin texture, while topical applications, including blends with vitamin C, can soothe dry skin and protect against sun damage. In an animal study, researchers found the topical application of alpha-tocopherol to be more effective than internal supplementation at preventing UV damage.11 In another animal study, researchers found that a topical solution of alpha-tocopherol inhibited UVR-induced epidermal lipid peroxidation.12
Scientists have produced the best skin-protecting effects using a topical blend of vitamins E and C, especially when combined with a UVA sunscreen ingredient such as oxybenzone.13 According to one trial, topical application of the C-E combination completely protects against UVB-radiation-induced lipid peroxidation.14
But vitamin E's propensity to rapidly oxidise raises concern about potentially harmful effects of topical application. In one study, researchers tested alpha-tocopherol succinate and acetate (synthetic vitamin E) on UV-irradiated mice and found that the topical application enhanced, rather than prevented, photocarcinogenesis. The researchers speculate that instability of vitamin E esters at room temperature may have contributed to the contrary findings. They call for more studies and consideration of the potential danger by manufacturers who include vitamin E esters in creams and lotions.15
DIMETHYLAMINOETHANOL (DMAE) made its debut years ago as a cure-all antioxidant aimed at enhancing cognitive functioning and reducing fatigue and depression. Nicholas Perricone, MD, author of The Perricone Prescription, claims that it is even more potent topically, adding to DMAE's credentials as a membrane stabilizer, anti-inflammatory and penetration enhancer.
A young face is characterized by short, thick muscles that prevent sagging. As we get older, the muscles get thinner and longer, causing a flatter and increasingly saggy face. Cosmetic surgeons cut muscles shorter to pull up the sags and round out the face.
"DMAE stimulates the contraction of muscles so you correct the sagging and get a more rounded look and a physiologically younger face," Perricone says, based on his 15 years of private practice and research. A possible mechanism of action is DMAE's stimulation of acetylcholine, a key component in muscle contraction. Perricone also says DMAE helps stabilize skin-cell membranes. An animal study found that one of DMAE's actions is to limit the tissue-damaging cross-linking of proteins by scavenging hydroxyl radicals.16
In a recent, unpublished, Johnson & Johnson-funded, controlled study presented at the AAD's 2002 annual meeting, researchers reported a 75 to 90 per cent facial improvement in the eye area, as well as improvements in facial lifting and contouring following topical application of DMAE for one week. The test included 33 subjects aged 36 to 59, and improvement ratings were calculated by expert evaluation of before-and-after photographs.17 DMAE's safety and efficacy was confirmed in a follow-up study in which 156 subjects aged 35 to 60 underwent an 18-week, double-blind, placebo-controlled study. At 16 weeks, the DMAE group showed significant improvement in overall skin appearance and the reduction of forehead-frown lines. Subjects continued to use DMAE for 12 months, at which point cumulative assessments confirmed DMAE's safety as a topical ingredient.18 An animal study found DMAE to be non-toxic and non-allergenic to the skin.19
In a recent randomised, double-blind study, researchers found that the application of a gel containing three per cent DMAE on human skin increased the skin's resistance to stretching, citing DMAE as a potential skin-firming agent.20
Though published DMAE research is scant, Johnson & Johnson's interest in its topical benefits supports Perricone's prediction that it could be one of the next big anti-ageing ingredients for skin.
CO-ENZYME Q10 has some research to support topical amelioration of periodontitis. In one study, 10 male patients with a combined total of 30 periodontal pockets received Co-Q10 in all pockets for three weeks, then Co-Q10 in 20 pockets and soybean oil in the remaining 10 for six weeks. Improvement in fluid levels and detachment loss occurred after the first three weeks and continued throughout the study using Co-Q10, but did not continue with soybean oil.21
In an animal study, researchers found that treating rabbit corneas with a topical Co-Q10/vitamin E blend prior to radiation exposure decreased the incidence of corneal cell death. 22 These studies indicate Co-Q10 may be an effective topical agent, though additional research specifically related to skin care is warranted. A German review determined that Co-Q10 is a viable photoprotectant with the ability to penetrate into the skin, protect collagen and reduce wrinkles in human skin. 23
FATTY ACIDS, specifically linoleic acid and gamma linoleic acid, are required for the skin to retain moisture. Science has found that linoleic acid is necessary to the enzymatic activity that develops skin cells into proper water-maintaining barriers.24 A deficiency of linoleic acid is characteristic of dry skin.25 Studies have found that a deficiency of linoleic acid is linked to conditions of poor skin such as acne.26 When applied topically, these two compounds reduce trans-epidermal water loss.27
Linoleic acid is also a major component of dermal ceramides, the binding 'mortars' between cells that provide both skin strength and barrier function.28,29 An animal study found that essential fatty acid-deficient skin has a weakened water-retaining barrier and that linoleic acid applied topically metabolizes into ceramides and unsaturated omega-hydroxy fatty acids, restoring the moisture and barrier-integrity of the skin.30
The skin-inflammation disorder atopic dermatitis is partially caused by deficiency in ceramide production and the subsequent weakened barrier membrane.31 Ceramide balance is also linked to ageing skin. In an in vitro study, researchers took skin samples from the face, hand and leg of different-aged female Caucasians and found an age-related decrease of all lipids and an altered ceramides-to-fatty acids ratio, which they claim causes the loss of skin-barrier function with age.32
Researchers at the University of California, San Francisco, tested a topical, ceramide-dominant, lipid-based emollient on 24 children with atopic dermatitis. After three weeks, 22 children showed a reduction in trans-epidermal water loss with improvements in skin integrity and hydration. Improvements continued through six and 21 weeks.33
Well-known skin care companies such as Borlind of Germany are now including plant-derived ceramides as novel topical ingredients in premium formulas.
HYALURONIC ACID (HA) is a disaccharide (alternating sugar-like molecules of glucosamine and glucuronic acid) that is the major water-holding molecule in the dermis and epidermis as well as all connective tissue and synovial fluid and in the vitreous gel that fills the eye. HA was long thought to be an inert filler in body fluids and connective tissues, but recent findings show it also plays an important role as an active anti-inflammatory compound.
Injected forms of HA have been used for arthritis, wrinkle-removal and ophthalmic surgery, and research supports its critical role in scarless wound healing.34Small facial cuts heal without scarring because of high HA levels. HA's multi-faceted role in wound repair—carefully regulating inflammation, formation of granulation tissue, re-epithelisation and remodeling—has prompted its topical use.35
Researchers in one study found that the combination of HA and diclofenac—a pharmaceutical benzeneacetic acid derivative indicated for osteoarthritis and ankylosing spondylitis—was effective at treating actinic keratoses, potential precursors to squamous cell carcinoma. Of the 29 subjects studied for six months, 81 per cent had a complete response and another 15 per cent showed marked clinical improvement.36
Other skin-deep treatments
Beyond the most familiar and most commonly used skin care ingredients, other herbs and ingredients are showing their face on the anti-ageing scene. Sabinsa Corporation has recently entered the skin care market with herbal preparations. One ingredient being used is boswellin from the plant Boswellia serrata. When tested on mice, researchers found it acted as a topical anti-inflammatory.37 Curcumin, which had the same effect,37 is being offered by Sabinsa as a patented, colour-free ingredient under the name tetrahydrocurcuminoids.
The French company Arkopharma offers the topical ingredient Hodeol, a patented fatty acid (9-hydroxy.10.12-octadecadienoic acid) extract from ivy, which it markets as a cellulite reducer. In a company-funded study, 21 women 25 to 49 years old applied Hodeol daily for 24 days. The results included an average 1cm reduction in thigh circumference and a report by participants of increased suppleness, firmness and smooth appearance. 38
Green tea, though a popular topical inclusion based on its health and antioxidant merits, still awaits more scientific research. However, the outcome of an experimental study showed that green tea's polyphenolic compounds, including epigallocatechin-3-gallate, protect against chemical carcinogenesis and photocarcinogenesis in mouse skin.39
Alpha-lipoic acid (ALA) is another compound touted as a potential winner in the future facial market. An animal study confirms the effective penetration of ALA into the skin as well as the immediate conversion of ALA to dihydrolipoic acid (DHLA).40
"The effectiveness of lipoic acid is believed to be from its by-product, DHLA," says Leslie Baumann, MD, director of cosmetic dermatology at the University of Miami. "DHLA has a more powerful anti-oxidative effect in the skin."
An in vitro study conducted at the Univeristy of California, Berkeley, researchers found that ALA selectively activated NF-kappaB, preventing photo-oxidative damage in UVB-exposed human skin.41
Baumann is currently studying the topical use of ALA for repairing photodamaged skin. "Preliminary results of our unpublished trials indicate that the use of topical lipoic acid has comparable results to glycolic-containing products," she says.
In a human study, a 12 per cent glycolic acid cream was found to elicit an SPF of 2.4 and improve photodamaged skin by 16 per cent within seven days.42 In a double-blind, randomised, placebo-controlled human study, 75 volunteers used either a five per cent glycolic acid topical or placebo on the face and neck for three months. The test group reported overall improvement in the reduction of photoageing characteristics including statistically significant improvement in skin texture and discoloration and a trend toward reduction of wrinkles.43
Although supported by smaller or company-funded studies, the inclusion of lesser-known topical ingredients in the anti-ageing skin care arena is a sure sign that the studies are positive enough for companies to risk creating products using them and that this market segment is expanding. Along with the old stand-bys, a host of new cosmeceuticals—some deemed efficacious, some awaiting further research—are now already adding value to creams, lotions and soaps.
Chris O'Brien is a researcher and writer in Rollinsville, Colorado.
References
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35. Chen WY, et al. Functions of hyaluronan in wound repair. Wound Repair Regen 1999 Mar-Apr;7(2):79-89.
36. Rivers JK, et al. An open study to assess the efficacy and safety of topical 3% diclofenac in a 2.5% hyaluronic acid gel for the treatment of actinic keratoses. Arch Dermatol 1997;133:1239-42.
37. Huang MT, et al. Inhibitory effect of curcumin, chlorogenic acid, caffeic acid, and ferulic acid on tumor promotion in mouse skin by 12-O-tetradecanoylphorbol-13-acetate. Cancer Res 1998;48(21):5941-6.
38. Jacquet A. Clinical evaluation of the efficacy and tolerance of a 15% Hodoel solution, applied topically. Arkopharma Laboratories 1996; Bordeaux, France.
39. Katiyar SK, et al. Green tea and skin. Arch Dermatol 2000;136:989-94.
40. Podda M, et al. Kinetic study of cutaneous and subcutaneous distribution following topical application of [7,8-14C]rac-alpha-lipoic acid onto hairless mice. Biochem Pharmacol 1996 Aug 23;52(4):627-33.
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