Cosmeceuticals: The New Medicine of Beauty (2024)

Abstract

Cosmeceuticals represent a new category of products placed between cosmetics and pharmaceuticals that are intended for the enhancement of both the health and beauty of skin. Encompassing an ever-increasing part of the skin care industry, cosmeceuticals are formulated from a multitude of ingredients, the main categories of which are discussed in this article. Given the growing interest in these products among patients and the strong claims made by manufacturers, it is important that physicians recognize these agents and understand their benefits, limitations, and potential adverse effects.

Introduction

The American population is becoming older and more affluent than ever. With many people willing to trade wealth for youth, there has been a surge in demand for high-end anti-aging products, and the skin care industry has responded in force. Moving beyond traditional cosmetics—which only temporarily adorn and beautify the skin—cosmetics companies have tapped into the biomedical revolution, adding biologically active ingredients to their products that enhance the function of healthy skin. Because these products are not intended to improve or to cure diseased skin, they have avoided pharmaceutical regulation and scrutiny. Thus, “cosmeceuticals” blur the line between drug and cosmetic, doctor and aesthetician, and patient and consumer.

Patients can flounder in the flood of new products, finding it difficult to select the right product and becoming frustrated when a product fails to produce its beneficent effect. Patients remain enthusiastic about these products, however, and seek their physician’s help in choosing the best products available. Physicians educated in these cosmeceuticals can serve their patients by (1) managing expectations to realistic, evidence-based effects and (2) warning against and monitoring for potential side effects.

There remains much controversy surrounding the “active ingredients” found within cosmeceutical products, particularly in regards to their mechanism of action, formulation, optimal concentration, penetration and retention in skin. Some clinical trials and tests have been done to address these questions, but on the whole there is little validation to support cosmeceutical claims. In vitro testing for some products has shown that these ingredients do have a protective and repairing effect on aging skin; however, there has been little translation of this evidence into in vivo testing to determine the possibility of delivering adequate doses to skin that will produce clinical or histologic results.¹

Vitamins

Many cosmeceutical agents are developed and advertised for prevention and treatment of aging skin, particularly photoaging skin. Photoaging refers to the damage that is done to the skin from prolonged exposure, over a person’s lifetime, to solar UV radiation. While the most important protective measure against photoaged skin is the daily application of UVA and UVB sunscreen, potential treatment options for already damaged skin involve the use of topical antioxidants and compounds that help repair DNA and stimulate collagen synthesis. Topical vitamins are substances that are purported to provide some of these benefits.

The efficacy of topical synthetic Vitamin A or retinoids—in various forms such as tretinoin, adapalene, and tazarotene—is evidence-based, and the cosmetic benefits of these prescription retinoids are well supported by ample research.^2,3 Tretinoin induces production of type I and II procollagen in skin and reduces collagen breakdown by inhibiting metalloproteinases. The overall effect is a thickening of the dermis as the skin is “filled in” with glycosaminoglycans, helping to reduce fine lines and wrinkles.

Other retinoids, such as retinaldehyde, retinol, and the retinyl esters, are marketed as over-the-counter cosmeceuticals and may have similar actions to their prescription counterparts despite having less evidence proving their efficacy.¹ Patients should be cautioned that all of the retinoids are able to produce skin irritation and dryness, even in over-the-counter formulations, although the latter much less than prescription-strength products.

Vitamin E is another vitamin that is purported to have advantageous cosmetic effects on skin. Functioning as an epidermal antioxidant by absorbing the solar spectrum of UV light, endogenous Vitamin E becomes depleted after years of excessive exposure to free radicals, with resulting oxidative damage. Thus, many studies have looked at the benefit of applying topical Vitamin E, especially in its most active form alpha-tocopherol, as a means of protecting against sunburn and improving the wrinkling and hyperpigmentation caused by free radicals. Studies in human subjects have demonstrated its efficacy in preventing UV-induced skin erythema, with topical 2% Vitamin E reducing the redness value by approximately 20%.⁴ A four-month facial study of topical 5% vitamin E resulted in improved wrinkling and UV-caused inflammation around the eye area.⁵ Importantly, Vitamin E can reduce UV-associated erythema and edema when applied before UV exposure, with little benefit noted if Vitamin E is applied after the exposure.⁶ Also, almost no side effects have been reported from the use of topically applied vitamin E.

One of the most recently recognized “cosmeceutical vitamins” is Vitamin B₃, also called nicotinamide or niacinamide. A precursor to the key metabolic cofactor NAD(P) and its powerful reduced form NAD(P) H, niacinamide’s role as a key player in antioxidizing reactions has been the focus of most of the studies. Well-tolerated in topical form, niacinamide has been shown to improve skin barrier by increasing lipids and epidermal protein.⁷ This action leaves skin more resistant to irritation and blotchiness, most likely by decreasing water loss from skin. Niacinamide also reduces facial dyspigmentation via a mechanism that inhibits melanosome transfer from melanocytes to keratinocytes.⁸ Other beneficial effects with chronic topical niacinamide application include improvement and prevention of skin yellowing and a smoothing of skin texture. However, even with these benefits, topical niacinamide remains one-third to one-fifth as effective as topical 0.025% tretinoin.⁹

Vitamin C, also known as L-ascorbic acid, is one of the vitamins that humans must obtain from dietary sources. However, oral supplementation of Vitamin C only minimally increases its concentration in skin. Thus, topical Vitamin C application is a popular research area. In addition to its well-known and essential contribution to collagen biosynthesis, research data demonstrates that topical Vitamin C has anti-inflammatory and antioxidant properties,¹⁰ such that it has been used to reduce the erythema associated with postoperative laser resurfacing. A double-blind, placebo-controlled, splitface 12-week study examining the effects of topical 3% ascorbic acid showed that Vitamin C is well-tolerated in topical application and causes a reduction in facial wrinkles.¹¹ Higher doses of 5–17% ascorbic acid revealed improved skin texture and the appearance of photoaging. With ongoing research confirming and maximizing the benefits of topical Vitamin C and the other cosmeceutical vitamins, these agents will continue to grow in their usefulness and value in protection and restoration of skin.

Hydroxy Acids

The hydroxyacids—comprised of the α-hydroxyacids, β-hydroxyacids, polyhydroxyacids, and bionic acids—represent a class of compounds with unprecedented cosmetic benefits. The most well-known and commonly used is the α-hydroxyacid glycolic acid for its proven antiaging benefit and ability to improve hyperpigmentation and acne-prone skin. Both the α-hydroxyacids and β-hydroxyacids work by removing or decreasing hyperkeratinized skin and restoring the epidermis, making them useful for treatment of dry skin, verrucous growths, and ichthyosis.¹² Furthermore, application of hydroxyacids causes dermal thickening by stimulating biosynthesis of glycosaminoglycans, collagen, and elastic fibers, improving wrinkles and fine lines.¹³ The polyhydroxyacids and bionic acids are newer agents with the same benefits as the α-and β-hydroxyacids but without their characteristic irritation or burning and with additional antioxidant and barrier functions to improve moisturization. Their gentleness on skin makes them ideal for treating sensitive skin. Gluconolactone is a polyhydroxyacid widely used in skin care products that has been shown in vitro to protect against UV radiation by trapping free radicals.¹⁴ The hydroxyacids, especially glycolic and lactic acid, are commonly used as peeling agents. Applied to the skin in high concentrations for short periods of time, hydroxyacid peels are increasingly used to accelerate exfoliation and to stimulate skin renewal to improve hyperpigmentation and texture of skin.

Peptides

The role of peptides in cosmeceuticals revolves around the hypothesis that peptide fragments of collagen and elastin can act as positive feedback signals for their own continued synthesis. Peptides are highly successful in the current cosmeceutical market, and there are increasing numbers of double-blinded, placebo-controlled studies to examine their effects on human skin. Peptides of interest include pal-KTTKS (Matrixyl), Ac-EEMQRR (Argireline), and Cu-GHK. The peptide pal-KTTKS is a fragment of dermal collagen that stimulates new collagen synthesis in vitro and is postulated to facilitate wound healing.¹⁵ It has high potency and was shown to improve wrinkled skin when applied topically at very low doses and with minimal skin irritation. Cu-GHK is also a fragment of dermal collagen, and the copper moiety is a necessary cofactor for collagen synthesis. Many peptides, such as Ac-EEMQRR, mimic botulinum toxin and function to cause muscle relaxation by inhibiting neurotransmitter release;¹⁶ however, a 2006 study comparing topical nonprescription products, including those containing peptides, to botulinum toxin type A injections concluded that the injections provided significantly greater efficacy and patient satisfaction in the treatment of glabellar frown lines.¹⁷ The cost of all of these peptides remains a challenge to cosmeceutical companies, especially if the peptide has low potency and requires greater concentrations to achieve efficacy.

Growth factors

Growth factors function as regulatory proteins that mediate signaling pathways, particularly those associated with wound healing. Kinetin, also known as N-6 furfuryladenine, is a plant growth factor studied in human skin fibroblast cultures. In vitro studies have demonstrated that the continuous application of kinetin may have the ability to delay the skin changes associated with aging as well as decrease the severity of these changes. Kinetin prevents the alteration in cell size and shape and delays growth rates and macromolecular synthesis associated with aging. Kinetin acts as both an inhibitor of free radical formation and a scavenger of reactive oxygen species by mimicking superoxide dismutase. Other clinical studies have suggested that topical kinetin may improve skin texture, decrease hyperpigmentation, and impede transepidermal water loss, but the mechanisms for these actions have much less evidence to support them.¹⁸

Botanicals

Cosmeceutical agents derived from plant sources make up an increasing niche in the cosmetic market. A huge variety of botanical products exists, and many claims are made regarding their dermatologic benefits; however, few studies have been conducted to substantiate these claims and examine the safety and efficacy of these ingredients.

Among these botanical substances, Ginkgo biloba, silymarin, ginseng, soy, and green tea have exhibited capacity to promote skin health and appearance. Ginkgo biloba is a common botanical added to moisturizers for its anti-inflammatory and antioxidant properties.

Although no controlled trials exist regarding the cutaneous benefits of Ginkgo biloba, studies carried out in vitro have shown that topical G. biloba extracts stimulate fibroblast proliferation and collagen synthesis.¹⁹ Silibinin, or silymarin, is a phytochemical from the milk thistle plant Silybum marianum that exhibits strong antioxidant activity and has been shown in various studies to neutralize toxic effects of different chemicals and UVB radiation in skin.²⁰ Ginseng is another botanical that has demonstrated significant dermatologic potential when applied topically, with the apparent action of reversing the manifestations of decreased hyaluronan levels that occurs with aging; other in vitro studies show that ginseng extracts have the ability to inhibit melanogenesis in melanoma cells, suggesting a possible role as a depigmentation or whitening agent for skin.²¹

Soy and its isoflavones have been purported to have a variety of dermatologic benefits, many of which are ascribed to its antioxidant effects and the estrogen-type action of its metabolites. Its phytoestrogen effect is thought to be mediated by binding to estrogen receptors in the cell’s nucleus, potentially slowing the skin thinning and collagen loss that occurs post-menopause. Soybean protease inhibitors and soy milk have been found to have depigmenting activity as well as the ability to reverse UV-induced hyperpigmentation.²² Lastly, green tea polyphenols are being aggressively marketed for their antioxidant and anti-inflammatory properties, which include limiting UV-induced lipid peroxidation in vitro.²³ There is also evidence that green tea polyphenols inhibit the activity of collagenase and increase biosynthesis of collagen in human fibroblasts.

Thus, all of the above botanical cosmeceuticals have been shown to influence mechanisms on skin that repair or prevent aging effects. For many of these products, however, there has yet to be a split-face, double-blind, randomized trial involving different concentrations of these ingredients and reporting side effects on which to base recommendations for use of these products.

Conclusion

Cosmeceuticals offer both challenges and rewards to patients and their physicians. As society holds a youthful and healthy appearance to be of utmost importance, many people feel anxious about their aging skin and seek physician advice on what to do.

Helping patients understand the degree of improvement that can realistically be achieved as well as potential side effects remains the primary responsibility of the physician with regard to these products. Many of the new cosmeceuticals in development sound very exciting, but the physician’s concern is to help patients choose the best products available today.

Some experts recommend that physicians pick one or two products with which they have experienced good results and advise their patients on how to incorporate them into their daily skin regimen--always reminding patients that even a safe product can evoke redness, cause irritation, or clog pores if used inappropriately.

As technology advances and cosmeceuticals continue to become more sophisticated and more widely used, the medical profession must continue to take an active role in familiarizing themselves with these products and in educating patients about the benefits and risks of cosmeceuticals.

Biography

Footnotes

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