Regulating Advances in Anti-aging

The concepts of “anti-aging” and the “reduction of old age” have gained popularity over the years, especially since people are living much longer. These terms have also grown to incorporate more aesthetic features of the skin as opposed to just wrinkles. In a September 2013 GCI magazine article, Phillip Mitteness states that anti-aging has evolved to include, “age spots, hyperpigmentation, dry skin, uneven skin tone, dark under-eye circles and even hair damage.” It is expected that the anti-aging product market will expand to more than US $290 billion in 2015. However, with the recent boom in technological and scientific discoveries, many of these new products are being engineered to produce results that are caused by changes in the user’s cells. If these innovations are effective and actually produce structural changes in the skin, are they still cosmetic products?

From a regulatory point of view, the functions of these products are on the borderline of therapeutic and cosmetic, as defined by the U.S. Food and Drug Administration (FDA). Beauty product manufacturers are using a variety of different ingredients to produce anti-aging effects. In a recent article, Garth Fisher, MD, a board-certified plastic surgeon in Beverly Hills, California, and co-founder of CellCeuticals Skin Care Inc., mentions several different anti-aging ingredients that he claims are effective, including: peptides, retinol, antioxidants and sunscreen. In addition to these, caffeine, dimethylethanolamine (DMAE) and radio frequency (RF) devices have been found effective in anti-aging products, particularly those designed to fight cellulite. This column will discuss these technologies and address a potential regulatory approach.

Peptides

As the human body ages, the skin begins to slow down the production of collagen and elastin, which are responsible for maintaining the smooth and “youthful” look of skin. With low levels of these substances, wrinkles may develop as a common sign of aging. Peptides, which are small strands of proteins, have been used in anti-aging products to promote additional production of collagen and elastin in an attempt to remove wrinkles.

In most cases, these peptides work by activating the collagen production pathway in fibroblasts, which are located in the upper layer of skin. The peptide binds to signal receptor proteins on the fibroblast membrane, activating the production of collagen. Of course, there are many different types of peptides possible; therefore, different peptides may range in effectiveness. On top of stimulating collagen production, peptides may be used for various other purposes such as stimulating growth factors and antioxidant enzymes.

Retinol

Another popular anti-aging ingredient is retinol, a form of vitamin A. Although initially found effective against acne, retinol is also used to fight the appearance of wrinkles and reduce cellulite.

However, it is not the retinol that directly does all the work. The retinol must first be broken down into retinoic acid, which has the ability to bind with receptor proteins and initiate biochemical processes within the skin cells, promoting them to function in the same fashion as younger skin cells would. This, in turn, is what causes the reduction of wrinkles, or “anti-aging” effects. Retinoic acid is also available in its pure form but this requires a prescription.

Well-known dermatologist and founder of the Murad skin care brand, Howard Murad, MD, advises that retinol products should only be taken at night, as retinol is photosensitive and may be inactive if exposed to excess light. Murad also advises that retinol and retinoic acid can cause skin irritation, and that non-prescription retinol may be used as a weaker alternative (as opposed to pure retinoic acid), to ease possible discomfort. According to Murad, the use of these products may cause skin to “peel, flake, turn red and become dry during initial use.” In addition to its applications in anti-aging, retinol is popular in anti-cellulite products due its ability to improve collagen production.

Antioxidants

Inevitably, the body is often exposed to harmful materials such as those found in pollution or smoke, which cause oxidation in the cells. A harmful chemical may interact with human cells by drawing electrons from other molecules that are part of the cell. The molecules that lose their electrons are known as free radicals, or oxidants. These free radicals can be attracted to other molecules necessary for biological functions as they search for electrons to stabilize themselves.

By removing electrons from the molecules necessary for cellular functions, the molecules destabilize, which can cause severe damage to the cell. Antioxidants help to diminish the effects caused by free radicals by providing electrons to the oxidants, hence stabilizing them and preventing further reactions. Numerous studies have shown that antioxidants help reduce the risk of cancer, and also help restore the look and feel of the skin. Of course, there are a number of different types of antioxidants, each with their own specific functional purpose. Some popular antioxidants include vitamin E, vitamin C and even retinol.

Sunscreens

Excess UV light exposure is known to damage the skin, and is a leading cause of skin cancer. Therefore, sunscreens have been developed to protect the skin from UV exposure. High levels of exposure to UV light damages fibroblasts and reduces collagen and elastin content, causing skin aging. In addition, the production of MMP1 collagenase is stimulated by UV light, which is responsible for degrading the extracellular connective tissue, resulting in looser, less elastic skin. Protecting the skin from harmful UV radiation can help to maintain the young and healthy look of skin.

Caffeine and Dimethylaminoethanol

Cellulite formation is a common occurance in women of all ages. For this reason, the beauty industry has developed numerous methods for reducing cellulite, including cosmetic creams containing active ingredients. Ava Shamban, MD, an assistant professor of dermatology at the University of California at Los Angeles, claims that these creams can only reduce the appearance of cellulite, but not prevent it entirely.

In addition to retinol, popular anti-cellulite ingredients are caffeine and dimethylaminoethanol (DMAE). The application of caffeine in topical skin care is useful due to the caffeine’s lipolytic activity on the skin. According to a study performed by Velasco et al., topical application of a product containing caffeine was found to reduce fat cell diameter by 17%.

The concept behind DMAE is to strengthen and promote firmer muscles. When combined with amino acids, DMAE causes muscles to contract, resulting in a reduced appearance of cellulite. However, according to Gary S. Brody, MD, a plastic surgery professor at the University of Southern California, cellulite is a natural occurrence and appears in people of all sizes. Although these topical products are formulated to reduce cellulite, evidently more powerful products are desired based on other innovations in the industry.

Radiofrequency Devices

Although creams can hide the look and feel of cellulite, some slightly more invasive techniques are capable of reducing cellulite and other unfavorable skin characteristics. Advances in radio frequency technology have made their way into the beauty industry, with the intent of improving the look and feel of the skin.

Radio frequency emitting medical devices have been developed to enhance the firmness and tightness of skin as well as reduce wrinkles. Marina Vashkevich, MD, member of the American Academy of Anti-Aging Medicine and owner of Toronto-based Med V Spa, has been using radio frequency medical devices to remove fat, and improve the look and feel of skin. Vashkevich explained that the device works by targeting two types of cells: fibroblasts and adipocytes. The radio frequencies stimulate the production of collagen in the fibroblasts while destroying fat cell deposits. This results in a much younger-looking body, while at the same time reducing fat and cellulite. This new technology is quickly picking up in popularity, and may become an alternative or adjunct to using anti-aging creams.

Regulations

Although many of these anti-aging technologies are great innovations, can they still be called cosmetics? Innovators all over the world are incorporating science and technology in their products to achieve greater results, and perhaps more permanent effects. But is society diving into these products too quickly? How should product manufacturers think about testing for safety?

In Section 201, chapter 2, of the U.S. Food, Drug and Cosmetic Act, the FDA defines cosmetics as “articles intended to be rubbed, poured, sprinkled, or sprayed on, introduced into, or otherwise applied to the human body...for cleansing, beautifying, promoting attractiveness, or altering the appearance.”

It is clear that these new anti-aging and anti-cellulite products do fall under the FDA definition of a cosmetic. However, the FDA also defines drugs as “articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease" and "articles (other than food) intended to affect the structure or any function of the body of man or other animals."

Although “anti-aging” products are definitely not intended to cure or prevent a disease, many modern ingredients and devices are intended to alter the structure or function of the body, particularly the skin. The interaction of ingredients with skin cells to promote the production of collagen is just one example of an effect that alters the function of the body. Therefore, it is evident that some new anti-aging products may fall under the definition of both a drug and a cosmetic, or a medical device plus a cosmetic. The term “cosmeceutical” is often used to describe such drug-like cosmetic products. However, the FDA does not recognize this word under the law.

In the United States, cosmetic ingredients (except for color additives) do not require FDA approval, while drug products must undergo an extensive approval process. In Canada, Health Canada is hosting a consultation this fall to discuss new regulatory changes for cosmetics that are currently regulated as drugs. In China, cosmetics have been classified into two different categories, with each category requiring a specific amount of regulation. Talks to create even further classifications of cosmetics are already in the works in China.

Perhaps this is a regulatory trend that will be further developed in other parts of the world. Is it time to clearly define the minimal standard of testing for today’s innovative cosmetic products? And perhaps, like the European Union, the concept of cosmetovigilance should be globally embraced to learn and study adverse reactions. With the ever-increasing development of cosmetic science, regulations may need adjustment to keep pace with the amazing innovations in anti-aging skin care.