Cosmeceutical Critique

Using oral and topical cosmeceuticals to prevent and treat skin aging, Part I

Publish date: December 12, 2017

Polypodium leucotomos (PL), an oral extract derived from ferns, has been demonstrated to display photoprotective effects at an oral dose of 7.5 mg. PL has consistently exhibited antitumor and skin protective effects.⁸ A 2004 study in humans revealed that two oral doses of PL contributed to a significant reduction in DNA damage after UV exposure,⁹ and a 2017 study showed that PL protected skin DNA from UVB.¹⁰ Although PL has been linked to topical benefits, it is the oral form that is most often used to protect skin.

Ascorbic acid, also known as vitamin C, has been amply demonstrated to confer benefits when given both orally and topically. An acidic environment is necessary for optimal absorption. Topical application of ascorbic acid, along with vitamin E and ferulic acid, has been demonstrated to decrease the formation of thymine dimers.¹¹ Unlike other antioxidants, ascorbic acid also stimulates procollagen genes in fibroblasts to increase collagen synthesis.¹²

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Another potent antioxidant, curcumin, is being studied for mitochondrial protective properties. Curcumin is the principal curcuminoid of turmeric, pictured here.

Niacinamide, also known as nicotinamide, is an integral part of the niacin coenzymes nicotinamide adenine dinucleotide (NAD+), nicotinamide adenine dinucleotide phosphate (NADP+), and their reduced forms NADH and NADPH. These contribute to DNA production and repair and are involved in multiple other important enzymatic reactions. Topical niacinamide has been demonstrated to play a role in DNA repair¹³by providing cells with the energy that the DNA repair enzymes need to unwind the DNA strand, replace the nucleosides, and rewind the strand. Specifically, niacinamide is known to enhance DNA excision repair and repair of UVB-induced cyclobutane pyrimidine dimers and UVA-induced 8-oxo-7,8-dihydro-2´-deoxyguanosine.¹⁴ Niacinamide is used topically because oral forms of niacin have been found to provoke flushing.

EpiGalloCatechin-3-O-Gallate (also known as EGCG), the primary active constituent of green tea, has been demonstrated to induce IL-12 to increase the production of enzymes that repair UV-induced DNA damage.¹⁵ The proven photoprotective effects of topical and oral green tea include reducing UV-induced erythema, decreasing sunburn cell formation, and attenuating DNA damage.¹⁶

Preventing and treating mitochondrial DNA damage

UV radiation elicits mitochondrial DNA damage known as the “common deletion.”¹⁷ Damaged mitochondria produce harmful free radicals known as reactive oxygen species. Mitochondria damage caused by ROS decreases the mitochondria’s ability to generate ATP energy, which is necessary for DNA repair and other cellular processes.

Free radicals and UV radiation damage mitochondria, as does normal cellular metabolism. The range of damage includes mitochondrial DNA impairment, loss of mitochondrial enzymes, and decreased ATP production. This leads to less energy for DNA repair and other reparative processes. While there is no established way to reduce mitochondrial damage once it has occurred, several research initiatives to achieve this end are underway. Currently, protecting the mitochondria from harm with sunscreens and antioxidants is the best option.

Antioxidants are effective in preventing the damaging effects of free radicals on vulnerable mitochondria. As a component of the mitochondrial respiratory chain and an antioxidant itself, coenzyme Q10 is particularly useful in this role. CoQ10 is available in both oral and topical formulations. Oral forms should be taken only in the morning because of a caffeine-like effect. Topical forms of CoQ10 have a dark yellow color that may be unappealing to patients. Polypodium leucotomos has been shown to lower the number of common deletions found in the mitochondria of irradiated keratinocytes and fibroblasts.¹⁸ The oral form is recommended. Another potent antioxidant, curcumin, is being studied for mitochondrial protective properties.¹⁹ Its strong yellow color and smell render it better suited for oral use although many companies are trying to develop cosmetically elegant topical formulations.

Scavenging free radicals

Ultraviolet light, pollution, and other insults engender free radical formation. Even sunscreen use has been linked to increased production of free radicals. Free radicals, also known as reactive oxygen species, harm cells in many ways including mitochondrial damage, DNA mutations, glycation, lysosomal damage, and oxidation of important lipids and other cellular components such as proteins. Antioxidants present various beneficial effects including scavenging free radicals, decreasing activation of mitogen-activated protein kinases, chelation of copper required by tyrosinase, and suppression of inflammatory factors, such as nuclear factor (NF)-kB.^20. Antioxidants are essential in preventing aged skin.

In summary, skin aging has many causes. Although they are not all understood, some of the processes have been elucidated. Next month, this column will focus on the prevention and treatment of inflammation and glycation, as well as reversing the effects of aging on skin cells.

Dr. Leslie S. Baumann

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002) and “Cosmeceuticals and Cosmetic Ingredients” (New York: McGraw-Hill, 2014). She also wrote a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems LLC.