Cosmeceuticals with Vitamins A and C for Aging Skin

By Marjorie D. Alschuler, PhD, and Melinda Ring, MD

In the united states, more money is spent on skin and hair products than on education. With the aging of the baby boomer generation, the number of cosmetics consumers is growing. Baby boomers are obsessed with youth, are health conscious, and believe that they will live longer than their parents. Catering to this quest for eternal youth, the cosmetic industry has adopted many ingredients that dermatologists have proven to be clinically effective in preventing and reversing the effects of aging on the skin. Two of these ingredients commonly found in cosmeceuticals are vitamins A and C.1

The term "cosmeceuticals" was coined about 20 years ago by Albert M. Kligman, MD, PhD, at the annual meeting of the Society of Cosmetic Chemists. Although the term has never been legally defined, it is widely used by dermatologists and the cosmetic industry to indicate those topical agents lying somewhere between pure cosmetics (e.g., lipstick and rouge) and pure drugs (e.g., antibiotics and corticosteroids). A cosmeceutical is a cosmetic product whose active ingredient is meant to have a beneficial physiological effect resulting from an enhanced pharmacologic action when compared to an inert cosmetic.1,2

Background

The two components of the aging process are intrinsic chronological aging, which is largely genetic, and extrinsic aging, which is caused by environmental influences, such as ultraviolet (UV) light, smoking, wind, nutrition, and chemical exposure.

Chronic UV light exposure contributes most significantly to extrinsic aging and causes coarseness, lentigines, fine lines, telangiectasias, and solar keratoses. In addition, poor arterial flow to the skin, usually the result of atherosclerosis, promotes these same lesions.

Vitamins A and C, together with vitamin E, are known as the antioxidant vitamins. Each works independently and in conjunction with other vitamins and may reduce free radical damage to DNA, which causes unwanted changes in the basic building blocks of cells and results in diseases from cancers to colds.

Vitamin A and its preventive role in night blindness were discovered in 1913. Vitamin A is one of a family of natural and synthetic derivatives collectively known as retinoids. It is a fat-soluble vitamin that occurs naturally in two forms: retinol and dehydroretinol.3,4

Vitamin C, also known as ascorbic acid, gained fame for its ability to cure scurvy, a vitamin deficiency disease particularly common among seamen who spent long periods of time away from fresh vegetables and citrus fruits. Because vitamin C is a water-soluble vitamin that the human body cannot synthesize, it should be obtained daily from food or supplements.3,4

  Table
Vitamins and skin care
Vitamin  Dietary Sources Skin Condition Results
Vitamin A Butter, egg yolk, fish oil, liver, green and yellow vegetables acne

Reduces frequency of outbreaks when applied topically or taken orally.

psoriasis

Condition may worsen during therapy initiation. May be used alone topically or orally, or combined with psoralens UV-A therapy to achieve results in patients whose conditions are unresponsive to either therapy alone. 

skin cancer  May prevent formation of new lesions when taken orally.
sun damage 

When applied topically, vitamin A helps skin repair itself faster; improves fine and coarse wrinkling; lightens brown spots; and reduces the number and size of actinic keratoses.

wound healing

Prevents or restores impaired wound healing caused by mediations when taken orally. Promotes an early inflammatory response.

Vitamin C Vegetables, citrus fruits skin cancer

Increases in dietary vitamin C have been shown to reduce UV-induced tumors. 

sun damage When applied topically, reduces fine lines and wrinkles, may lessen the severity of sunburns, and helps skin regenerate.
wound healing

Acts as a cofactor for lysyl and prolyl hydroxylase, which stabilize collagen.

Adapted from: American Academy of Dermatology. Vitamins play an important role in the prevention and treatment of skin conditions. Available at: http://www.aad.org/PressReleases/vitamins_prevention.html. Accessed October 4, 2001.

Mechanism of Action

Retinoids have many important biological effects such as regulating growth and differentiation in epithelial cells, diminishing malignant cell growth, and strengthening the immune system. A cytosolic receptor for retinoic acid, cellular retinoic acid-binding protein has been demonstrated in the epidermis and in dermal fibroblasts. Retinoic acid receptors, nuclear receptors specific for retinoic acid, bind to retinoids and exert their effects through differential gene modulation.5

Most of the research conducted on the effectiveness of retinoids has been in the treatment of acne. Prescription retinoids prevent the development of comedones, halting their progression to inflammatory lesions. Both oral and topical retinoids have been studied, though topical prescription retinoids are the mainstay for treating most of the common varieties of acne vulgaris.

Vitamin C, on the other hand, comprises equal amounts of the isomers L-ascorbic acid and D-ascorbic acid; however, only L-ascorbic acid can be absorbed percutaneously. Claims have been made that topical forms of vitamin C may reduce signs of aging, presumably by scavenging free radicals, which enhance skin carcinogenesis and photoaging and whose production is increased during exposure to UV light. In addition, vitamin C can affect the quantitative production of collagen, which normally is decreased in older skin.6

Vitamin C also is critical in wound healing and acts as a cofactor for several enzymes, including lysyl and prolyl hydroxylase, which stabilize collagen. Vitamin C levels commonly are low in older patients, which may contribute to slower and more difficult wound healing.7

Clinical Studies

Recently, controlled studies have shown that retinoids can reduce and prevent wrinkles, brown spots, and actinic keratoses. Kligman et al first noted the ability of tretinoin (trans-retinoic acid) to improve photoaged skin in mice.8 Human and in vivo studies confirmed that retinoic acid enhances the reparative processes in photodamaged skin.9

The first double-blind, vehicle-controlled trial of topical tretinoin in human photoaging was performed by Weiss et al in 1988.5 In a four-month study, 30 patients applied tretinoin 0.1% cream to one forearm and vehicle cream to the other. Clinical improvement was seen only in the tretinoin-treated skin (P < 0.0001). More than 90% of the patients presented with a retinoid dermatitis, which did not prevent them from completing the study. These studies have shown that topical tretinoin improves fine and coarse wrinkling, diminishes tactile roughness, lightens solar lentigines, and reduces the number and size of actinic keratoses. Patients reported noticeable improvement in skin texture and tone after starting a retinoic acid treatment program; those with more severely damaged skin showed the most improvement.

In 1997, Duell et al found topical retinol had increased skin penetration compared to retinoic acid, without the irritation caused by retinoic acid.10 These investigators concluded that retinol may become a clinically useful product due to its low irritation potential and potent retinoid activity.

Murray et al treated the volar forearms of 10 volunteers with a 10% L-ascorbic acid solution or vehicle control.11 After UVB irradiation, sites treated with topical vitamin C showed a significant reduction of the minimal erythema dose and a less intense erythematous response than controls. In other studies, human sunburn cells decreased and improvement occurred after three days of UV-B exposure to sites treated with 10% topical vitamin C 15-30 minutes prior to exposure.7

Adverse Effects

Although a minimum of 24 weeks of tretinoin therapy usually is needed to manifest visible signs of improvement, many patients discontinue therapy, thus reversing any positive results, because of untoward side effects, including irritation, dryness, and redness. A retinoid skin reaction consisting of xerosis and mild inflammation has been the only use-limiting side effect reported in photodamaged skin treated with topical tretinoid, and patients will tolerate the reaction best if they are informed in advance of its likely occurrence.5 Topical retinol use, on the other hand, produces less irritation.7 Topically, vitamin C is safe in high levels for prolonged periods due, in part, to its water solubility.

Regulations

Retinoic acid currently is the only medication approved by the U.S. Food and Drug Administration as safe and effective for reversing some of the effects of skin damage and is available only by prescription. Retinol, the parent compound, is metabolized in the body to retinoic acid and has "grandfather" status under the Dietary Supplement Health and Education Act of 1994, which allows retinol to be marketed without proof of safety and efficacy.

In addition, the cosmetic industry is not held to the same regulatory standards as the pharmaceutical industry. Drugs must establish minimum good manufacturing practices for each batch of finished product in regard to their active ingredient; cosmetics are not required to list the ingredients in each product. Although the cosmetic products do indeed contain vitamins A and C, they may not be formulated in the optimal doses, administered via the optimal route, or offer the chemical activity level proven effective in the controlled trials.

The U.S. cosmetic industry is regulated by the Federal Trade Commission and cannot engage in unfair or deceptive acts or practices regarding the promotion of its products.

Merchandising

Recent articles dispute the subjective claims of the cosmetic industry, which are difficult to measure clinically.1,2 Some contend that vitamin-containing products are natural appeals to consumers who are suspicious of anything synthetic and assume that a substance that is found naturally in the body will provide benefits when administered in large doses, either oral or topical. Furthermore, many well-formulated skin care products, regardless of their ingredients, may improve the appearance of photodamaged skin simply due to their basic formulations (i.e., good moisturizers enjoy the long- recognized benefits of emollients in moderating common skin conditions).1,2

To counter these criticisms, one company funded an independent research center whose purpose is to perform scientific investigations into the biology and physiology of healthy skin and to establish synergistic connections between dermatology and cosmetic research.12 Another joined with Harvard University and Massachusetts General Hospital (MGH) to establish the MGH/Harvard Cutaneous Biology Research Center.13

Although they do not cite specific studies, many cosmetic companies do make claims about the efficacy of their products in their brochures, advertisements, and web sites. Consumers can purchase both top-end ($50 and up) and lower-end ($16 for Avon Anew Line Eliminator Dual Retinol Facial Treatment) cosmetic products containing antioxidants and retinol to treat fine lines, wrinkles, dark spots, and uneven texture. Daytime products also contain sunblock SPF 15 or higher. Because retinol degrades in sunlight, products containing this ingredient are recommended for overnight application.

Conclusion

Retinoic acid, a derivative of vitamin A, has been shown to reduce and prevent wrinkles, brown spots, and actinic keratoses in controlled studies. Beginning with Weiss’s 1988 vehicle-controlled trial of topical tretinoin, clinicians have found significant improvement in patients’ skin texture and tone. However, a retinoid dermatitis, consisting of xerosis and mild inflammation, did occur in most patients. Recent studies have found that topical retinol has greater skin penetration than topical retinoic acid with potent retinoid activity and lower irritation potential. Topical vitamin C was shown by Murray et al to significantly reduce the erythmatous response to UV radiation, demonstrating its potential as a photodamage preventive.

Recommendation

Prevention is the best strategy for retaining healthy youthful skin. Avoid exposure to direct sunlight, use sunscreen with SPF of at least 15 year-round, and wear protective clothing. Advanced signs of aging may require prescription medications under the supervision of a dermatologist. Cosmetics containing vitamins A or C can provide some relief from the signs of aging while preventing further damage, and there appear to be no harmful side effects.

Dr. Alschuler is Medical Education Specialist and Dr. Ring is Clinical Training Attending Physician and Coordinator, CAM Curriculum, Internal Medicine Residency Training Program, St. Joseph Hospital, Chicago, IL.

References

1. Kligman AM. Cosmetics. A dermatologist looks to the future: Promises and problems. Dermatol Clin 2000; 18:699-709.

2. Kligman D. Cosmeceuticals. Dermatol Clin 2000;18: 609-615.

3. The antioxidant vitamins A and C. Altern Med Alert 2000;3(Suppl 12):S1-S2.

4. Draelos ZD. Adding vitamins to the mix: Skin care products that can benefit the skin. Presentation at the American Academy of Dermatology 2000 Annual Meeting. San Francisco, CA: March 11, 2000. Available at: www.aad.org.

5. Weiss JS, et al. Tretinoin treatment of photodamaged skin. Cosmesis through medical therapy. Dermatol Clin 1991;9:123-129.

6. Gendler EC. Topical treatment of the aging face. Dermatol Clin 1997;15:561-567.

7. Keller KL, Fenske NA. Uses of vitamins A, C, and E and related compounds in dermatology: A review. J Am Acad Dermatol 1998;39:611-625.

8. Kligman LH, et al. The contributions of UVA and UVB to connective tissue damage in hairless mice. J Invest Dermatol 1985;84:272-276.

9. Kligman AM, et al. Topical tretinoin for photoaged skin. J Am Acad Dermatol 1986;15:836-859.

10. Duell EA, et al. Unoccluded retinol penetrates human skin in vivo more effectively than unoccluded retinyl palmitate or retinoic acid. J Invest Dermatol 1997; 109:301-305.

11. Murray J, et al. Topical vitamin C treatment reduces ultraviolet B radiation-induced erythema in human skin [abstract]. J Invest Dermatol 1991;96:587.

12. Chanel Research Centre for the Study of Healthy Skin (CERIES). More information is available at: www.chanel.com/fb/html/en/newframeset.cfm?zone=USA&lang=EN. Accessed October 3, 2001.

13. Shiseido Annual Report 2000. Available at: www.shiseido.co.jp/e/e0009anu/html/indexp.htm. Accessed October 3, 2001.