Life Extension Magazine®

Issue: Jun 2005

Why Sunscreens Do Not Fully Prevent Skin Cancer

Misconceptions about sunscreens may be contributing to the epidemic of deadly skin cancers. Learn why most sunscreens do not protect against melanoma, and how topically applied antioxidants help guard against damaging sunrays.

By Dale Kiefer.

For decades, the public has been told that sunscreens help guard against skin cancer.

One would think that a lotion that reduced solar ray penetration would be protective. Recent scientific studies, however, suggest that sunscreen use may not reduce the risk of melanoma, the deadliest of skin cancers.1

Commercial sunscreens fail to adequately protect the skin because they have little impact on reducing the free radicals generated in response to solar radiation exposure. One study showed that an SPF 20 sunscreen provided a “free radical protection factor” of only 2!2 In other words, while sunburn-inducing ultraviolet-B rays can be blocked, other kinds of solar radiation continue to inflict DNA damage that can result in skin cancer.2,3 These same free radicals also contribute to skin aging.3,4

Since 1983, the Life Extension Foundation has maintained that it takes more than conventional sunscreens to protect the skin from DNA-damaging solar rays. The encouraging news is that an abundance of newly published data provides a basis for enhanced skin protection against ultraviolet light that greatly exceeds what is available in commonly used over-the-counter sunscreens.

Considering that skin cancer (malignant melanoma, basal cell carcinoma, and squamous cell carcinoma) is the cancer with the highest incidence worldwide, those who follow obsolete recommendations are setting themselves up for lethal disease or premature aging of the skin.5

In this article, Life Extension challenges conventional wisdom about how you can protect yourself against damaging solar rays. Alternatives to outmoded, topical sun-blocking agents are provided.

Misconceptions can be deadly. If you think you can safely lie out in the sun as long as you are covered with a commercial sunscreen, the science indicates you are mistaken. Increasingly, studies suggest that no commonly available sunscreen prevents photodamage.3

Even if you choose to avoid sunbathing, typical everyday exposure (30 four-minute exposures over the course of a week) is equivalent to spending over two hours every week at the beach. In fact, everyday sun exposure is a causative factor in skin aging.2,4

With the onset of the long, sunny days of summer and the ongoing depletion of the Earth’s protective ozone layer, protecting your skin against solar radiation should be a priority. As the incidence of skin cancers and premature aging of the skin continues to increase to epidemic levels, taking aggressive steps to guard against sunlight-induced free radicals is of paramount importance.

An estimated 90% of all skin cancers result from long-term exposure to UV radiation from the sun.6 Fair-skinned Caucasians and redheads, usually of northern European descent, are at highest risk of suffering UV-induced damage.

Melanoma Incidence Rising

Melanoma is highly treatable when detected and treated early. It is also largely preventable, if you scrupulously avoid sun exposure throughout your life. However, studies show that Americans have received up to 50% of their lifetime dose of UV radiation by the time they reach the age of 21.7 If you are of Caucasian descent and a certain age, you likely are at increased risk of developing this dangerous cancer of the skin’s pigment cells, which are known as melanocytes.

In fact, according to the National Cancer Institute, the incidence of skin melanoma among Caucasians in North America has steadily increased for about the last 30 years. Diagnoses increase dramatically after the age of 50, especially among men.8 Scientists at the Boston University School of Medicine report that in the US, melanoma diagnoses are increasing at a rate faster than those of any other preventable cancer.9

The American Cancer Society estimates that the mortality rate from melanoma has increased 50% since 1973. While the annual rate of increase has slowed somewhat since the early 1980s, nearly 60,000 new cases are expected to be diagnosed this year, and nearly 8,000 Americans will die of the disease.10 Those statistics pertain only to melanoma, the deadliest of skin cancers. If we also include basal cell and squamous cell carcinomas (two less deadly but still worrisome cancers of the epidermis), various skin cancers account for more than 50% of all cancer cases.

Melanoma may be deadly, but basal and squamous cell carcinomas are considerably more common. In fact, “Basal cell carcinoma is as common as dirt,” says Dr. Brett Coldiron, an expert on skin cancer treatment. Basal and squamous cell carcinomas respond well to relatively simple treatment, but repeat carcinomas likewise are common.

Why Tanning Is Damaging

Tanning results when melano-cytes generate pigment in an apparent effort to protect the skin. Efficiency at pumping out melanin confers darker skin, and darker skin traditionally has been associated with greater protection from the sun, primarily because darkly pigmented skin is at lower risk of photocarcinogenesis, or UV-induced cancer. By the time a tan develops, however, tissue damage has already occurred.

Recently, some scientists have suggested that melanin production is triggered by DNA damage and subsequent cellular efforts to repair that damage. According to this hypothesis, photoprotection against the redness and DNA damage caused by UV exposure does not correlate with level of skin pigmentation; instead, darker-skinned Caucasians may simply be better at repairing damage than are lighter-skinned individuals.11 Growing public awareness of the dangers of a “healthy tan”—and of the importance of regular use of sunscreen with a sun protection factor (SPF) of 15 or greater, in combination with skin-protective phytochemicals—may help to slow the incidence of skin cancer.

New, Improved Zinc Oxide

Various chemicals act as UV screens, and commercial sunscreen products may incorporate several of these to achieve a given SPF level. One of the oldest, best-known sunscreen agents is zinc oxide. Although perhaps none-too-fondly recalled as a white paste sported by lifeguards at the beach, zinc oxide has come a long way in recent years. New manufacturing processes can produce zinc oxide with microfine particles that block UV radiation effectively while appearing invisible on the skin.12,13 The FDA classifies microfine zinc oxide as a Category I skin protectant.

Also important for immune health is inorganic zinc, which is found in at least 300 proteins, hormones, and enzymes,14 including one of the body’s most important natural antioxidants, superoxide dismutase (SOD).15,16 Topical zinc apparently promotes healthy skin by at least two mechanisms besides UV protection. Animal studies have shown that topical zinc oxide prompts the release of insulin-like growth factor and increases the mitotic index of basal cells, while also promoting wound healing.17,18 The mitotic index measures the rate at which cells divide in order to repair tissues.

Titanium Dioxide

Like zinc oxide, titanium dioxide is an inorganic metal. While previous research suggested that these micronized oxides act as physical sun shields by scattering or reflecting UV light, recent findings suggest that zinc oxide and titanium dioxide mobilize electrons within their atomic structure while absorbing UV radiation.13 Thus, while these agents are not inert as was previously assumed, they are still safe, stable, non-toxic, and highly efficient sunscreens.13 Titanium dioxide offers a high level of protection against both UVA and UVB radiation, and scientists report that “products containing microfine titanium dioxide are likely to offer superior photoprotection.”19

Octinoxate and Oxybenzone

Octinoxate and oxybenzone are highly efficient ultraviolet shields that the FDA has qualified as Category I sunscreens. These compounds primarily offer protection against UVB waves. Investigators have found that octinoxate, also known as octyl methoxycinnamate, protects the skin against not only sunburn but also UV light-induced DNA alterations.20,21 Titanium dioxide also demonstrated this DNA-protective effect.21 When scientists compared the efficacy of several sunscreen agents, they found that preparations containing oxybenzone yielded the highest SPF values.22 Thus, octinoxate and oxybenzone may help protect against UV-light induced DNA changes and boost the SPF of sunscreen products.

Sunscreen agents including transparent microfine zinc oxide, titanium dioxide, octinoxate, and oxybenzone are clearly a boon to sun worshipers. For some people, however, the judicious use of sun blockers may simply be too little, too late, as sun damage is cumulative.23 Skin can be thought of as a kind of radiation dosimeter, such as an X-ray technician might wear. Although daily exposure may be minimal, invisible damage accumulates gradually. Like the X-ray technician, we need to keep cumulative dosage in mind when venturing into the sun.

Sunscreen: How Much, How Often?

A sunscreen with an SPF of 15 should prevent sunburn from an all-day exposure to tropical sunlight. Behavioral studies show, however, that sunscreens of SPF 15 or greater do not always prevent sunburn.24 Several factors may account for this discrepancy in sun protection, including the type of sunscreen applied, resistance to water immersion and sand abrasion, and how often sunscreen is reapplied.

A number of studies suggest that many people do not use enough sunscreen to obtain maximum sun protection. The FDA determines the SPF of a sunscreen based on an application thickness of 2 mg/cm2. A study from Denmark showed that when 42 volunteers on a beach applied their own sunscreen all over their bodies, the average amount applied was only 0.5 mg/cm2, or one quarter of the recommended amount.25 The application thickness of sunscreen has a significant effect on its sun protection factor. In fact, an English study showed that most people apply only enough sunscreen to achieve 20-50% of the sun protection factor expected from the product label.26 Underprotection due to inadequate application may explain the reports suggesting that sunscreen use is a risk factor for melanoma.26

While ample application of sunscreen is important, consistent daily use may be just as critical. Researchers from Boston and Cincinnati examined the effects of daily versus intermittent sunscreen application in preventing skin damage. Twenty-four subjects were exposed to two daily doses of UV radiation for four consecutive days. Three sunscreen products were applied to areas of each subject’s skin. A product with an SPF of 15 was applied daily before UV exposure.

To simulate intermittent product use, an SPF-15 product or SPF-29 product was applied to another area on three of the four days, with one missed application on days two, three, or four. The researchers found a significant increase in inflammation and sunburn in the intermittently protected areas compared to skin that was not exposed to UV light and skin that was treated daily with the SPF-15 product. The researchers concluded, “daily use of a sunscreen reduces the skin damage produced by UV exposure compared with intermittent use of equal or higher SPF products. The daily application of sunscreens in appropriate quantities reduces the harmful effects of solar UV radiation on skin.”27

What About Vitamin D?

Some health authorities have recently suggested that the campaign to encourage rigorous use of sunscreen may have an unforeseen side effect: an increase in vitamin D deficiency. It is true that occasional sun exposure is important for the body’s manufacture of vitamin D.28-30 In fact, 90-100% of the body’s requirement for vitamin D can be obtained by the action of UV light striking exposed skin.31 It is also well established that adequate vitamin D is essential for good bone health. Some scientists have even proposed that sunlight exposure confers a measure of protection against certain cancers—including, paradoxically, melanoma,32 possibly due to sunlight’s role in helping the body manufacture vitamin D.30,31

This issue, however, remains controversial. Dr. Coldiron believes that approximately 15 minutes of unprotected sun exposure per week is sufficient to meet the body’s requirements, given the level of vitamin D fortification in the food chain. Michael F. Holick, MD, PhD, a professor of medicine, physiology, and dermatology at Boston University Medical Center, agrees. In an article published in The American Journal of Clinical Nutrition, Dr. Holick writes: “Sensible sun exposure (usually 5-10 minutes of exposure of the arms and legs, or the hands, arms, and face, 2 or 3 times per week) and increased dietary and supplemental vitamin D intakes are reasonable approaches to guarantee vitamin D sufficiency.”33

Green Tea

While UV-mediated vitamin D manufacture is efficient, this important vitamin can also be obtained through dietary sources and supplements. Vitamin D is present in fatty fish, which likewise provide healthful omega-3 fatty acids, and as a dietary supplement and food additive. However, skin cancer is far more common than rickets, the soft bone disease that can result from vitamin D deficiency.34 Many aging baby boomers suffered severe sunburns as children, which places them at significantly greater risk of developing skin cancer as they approach the age of 50 and beyond.

Routinely applying sunscreen with an SPF of 15 or greater—and carefully re-applying it according to the manufacturer’s instructions—is essential to helping prevent skin cancer and premature skin aging. Although SPF represents the beginning of the modern sun-protection story, it is certainly not the end. As one team of scientists recently declared in the peer-reviewed medical journal Cutis, “Even those products with a very high sun-protection factor (SPF) and full-spectrum UVB and UVA protection may not prevent UV radiation-induced [damage to the immune system].”35

Recent research on cancer-fighting phytochemicals—potent, biologically active compounds derived from plants—indicates that a more proactive approach to skin health may be in order. By combining a variety of beneficial compounds with more mundane sun-blocking agents, it is possible to protect the skin from damage and actively repair some damage that already may have occurred.

Benefits of Topical Green Tea

Scientists have recently focused on several remarkable compounds that offer protection against photoaging and photodamage. Chief among these naturally occurring chemicals is epigallocatechin gallate (EGCG), a catechin polyphenol compound found in green tea. Studies have shown that EGCG provides broad-spectrum protection by preventing three of the pathological changes associated with sun damage: inflammation, DNA damage, and immune system deficits.36,37 According to one leading researcher, “Animal and human studies suggest that green tea polyphenols are photoprotective in nature.”38

Inflammation normally results with the exposure of skin to UV radiation. White blood cells known as leukocytes stream into irradiated tissues. Oxidative damage occurs and produces free radicals, thereby depleting immune system cells. Numerous studies have found that topical application of green tea extract prevents these pathological changes.38-45 As a result, researchers believe, green tea may prevent skin cancers that would normally be induced by exposure to solar radiation.38-45 Indeed, experiments on mice specially bred for their susceptibility to skin cancer demonstrate that topical application of green tea extract reduces tumor incidence and size following exposure to measured amounts of UV radiation.42,46 A leading dermatology research team concluded, “Treatment with EGCG . . . resulted in exceptionally high protection against photocarcinogenesis . . . ”42

Green tea’s benefits do not stop there. More recently, scientists examined green tea’s effects on normal, healthy skin in aging humans. Topically applied green tea extract stimulated the proliferation of skin cells known as keratinocytes. The increase in these structural support cells led to an increase in epidermal thickness, and subsequent UV exposure failed to destroy the cells, as would normally occur. Two of the hallmarks of aging skin are reduced thickness and keratinocyte destruction. Green tea reversed both of these markers of skin aging. The researchers concluded, “This study demonstrates that EGCG promotes keratinocyte survival and inhibits the UV-induced [cell death] via two mechanisms . . .”47

Earlier this year, researchers in England published the results of experiments in which human cell cultures were exposed to UV radiation with or without the presence of EGCG. Cells treated with the green tea compound experienced significant protection from UV-induced DNA damage. Scientists believe such damage may underlie the eventual development of cancer; it is likewise implicated in the development of visible signs of aging. Taking things a step further, human subjects were given green tea to drink, and their blood was collected before and after tea drinking. The blood cells were subsequently irradiated with UVA radiation. Blood cells drawn from subjects who drank green tea experienced significant protection from UV damage compared to those drawn before tea drinking.37

SKIN CANCER STATISTICS

Currently, a raging epidemic of cancer relentlessly kills one person every single hour of every single day.* While breast cancer and lung cancer quickly come to mind as contenders for the leading cancer killer, it is actually skin cancer that needlessly claims so many lives. Each year brings more new cases of skin cancer than cases of breast, prostate, lung, and colon cancers combined.* Yet skin cancer is largely preventable, and with a few easy steps, more than 60,000 needless deaths a year could be prevented.*

The statistics on skin cancer are nothing less than frightening:

• more than 1 million people will be diagnosed with skin cancer this year*
• more than half of all new cancers are skin cancers*
• one in five Americans will get skin cancer during their lifetime*
• melanoma kills more young women than any other cancer*
• there are more new cases of melanoma than of HIV/AIDS**
• the past 30 years have seen no significant advances in medical therapies or survival for patients with advanced melanoma**
• in national skin cancer screenings, 44% of those found to have melanoma are white men over the age of 50*
• the incidence of eye melanomas among white males increased 295% between 1973 and 1999*
• more than 90% of all skin cancers are caused by sun exposure, yet fewer than 33% of adults, adolescents, and children routinely use sun protection.*

References
* Available at: http://www.skincancer.org/skincancer-facts.php. Accessed April 11, 2005.
** Available at: http://www.melanoma.org/mrf_facts.pdf. Accessed April 11, 2005.

Silibinin, Silymarin Are Also Protective

The milk thistle plant (Silybum marianum) is another source of beneficial compounds. Silibinin and silymarin, flavonoid compounds extracted from milk thistle, have well-established antioxidant, anti-inflammatory, and immune-enhancing properties. Used clinically to treat liver toxicity in Europe and Asia, milk thistle flavonoids also combat carcinoma of the prostate and lungs, as well as other cancers.48-60

Aware that many antioxidants guard against tumor promotion, scientists at Case Western Reserve University wondered whether silymarin might also protect against skin cancer. In the late 1990s, they tested this hypothesis on mice bred for their susceptibility to skin cancer. After topical application of silymarin, scientists exposed the mice to chemical carcinogens known to elicit tumors. Tumor incidence, multiplicity, and volume were all reduced significantly. According to the research team, “These results suggest that silymarin possesses exceptionally high protective effects against tumor promotion . . .”49

Milk Thistle
(Silybum Marianum)

In the last few years, similar research has confirmed and expanded on these findings. Scientists at the University of Colorado reported that silibinin, a major constituent of milk thistle, significantly reduced skin tumor multiplicity and volume when applied to the skin of mice bred to serve as a model of UV-induced human skin cancer. Tumor incidence was decreased moderately, and the mechanisms underlying these protective effects were elucidated. According to the researchers, “Together, these results show a strong preventive efficacy of silibinin against photocarcinogenesis, which involves the inhibition of DNA synthesis, cell proliferation, and cell cycle progression, and an induction of apoptosis.”52

Working with cultures of skin carcinoma cells, researchers examined the effects of EGCG and silibinin on molecular signaling events involved in the rampant proliferation of the aberrant cells. While treatment with both phytochemical agents resulted in “strong dose- and time-dependent cell growth inhibition,”57 the scientists noted that cancer-preventive effects were achieved through different molecular mechanisms—a finding that supports combining photoprotective phytochemicals for maximum efficacy.

Because milk thistle flavonoids prevent skin cancer through various mechanisms and are well tolerated, they are a natural choice for inclusion in broad-spectrum sunscreen formulations. “Silymarin may favorably supplement sunscreen protection and provide additional anti-photocarcinogenic protection,” wrote a leading researcher earlier this year.48

Grape Seed Polyphenols and Proanthocyanidins

Resveratrol, which is found in grape seeds and skins, has been hailed as a remarkable compound capable of exerting a wide range of beneficial effects and extending life span in a variety of organisms.61,62 Scientists classify resveratrol and related compounds as phytoalexins: natural antibiotics designed to protect a plant from attack by pathogens. Researchers also believe that resveratrol protects plants from UV damage. For instance, grapes grown at higher altitudes, where UV exposure is greater, tend to contain greater amounts of resveratrol.63

Another class of beneficial compounds concentrated in grape seed, the antioxidant proanthocyanidins, inhibit skin chemical carcinogenesis and photocarcinogenesis in mice through at least three pathways.64-67 Proanthocyanidins have demonstrated antioxidant power that is 20 times greater than that of vitamin E and 50 times greater than that of vitamin C. These powerful phenolic compounds protect the skin against sun damage while promoting the elasticity, flexibility, youthfulness, and health of skin cells.67

Turmeric Root Extract

Throughout history, the curry spice turmeric (Curcuma longa) has been valued as both a culinary and medicinal agent. Curcumin, a yellow pigment derived from turmeric root, exhibits antioxidant and anti-inflammatory effects, and may help promote wound healing.68 In an experimental animal model, topical curcumin application inhibited the initiation and promotion of skin tumors.69

While these and other studies suggest that topical curcumin may benefit the skin, curcumin’s yellow color makes it undesirable as a cosmetic agent. Fortunately, researchers have developed a colorless derivative of turmeric root called tetrahydrocurcumin that may allow people to benefit from this spice without undesirable cosmetic effects. Topical application of tetrahydrocurcumin helps to quench existing free radicals and prevent the formation of new ones. This dual action protects skin cells from UV light-induced damage and resulting inflammation and skin injury.70

Laboratory studies indicate that topical tetrahydrocurcumin is a safe and effective skin-lightening agent.71,72 Skin-lightening agents help to fade sun-induced areas of hyperpigmentation, or skin darkening. Many such agents work by inhibiting tyrosinase, a key enzyme involved in melanin synthesis. Thus, the colorless turmeric root derivative tetrahydrocurcumin may help protect the skin against detrimental effects of UV light and may help prevent (or fade) hyperpigmented areas of skin. While hyperpigmentation is not a medically harmful condition, it is always advisable to have a physician examine new brown spots to rule out skin cancers.

Licorice (Glycyrrhiza Glabra)

Licorice Extract and Rosemary

Licorice, derived from the roots of Glycyrrhiza glabra, has been used medicinally for more than 4,000 years. Modern science has confirmed that licorice is a powerful skin protectant. Numerous studies suggest that licorice extract protects the skin from the damaging effects of UV light.73,74 Licorice extract also has demonstrated efficacy in treating atopic dermatitis, an allergy-related, intensely itchy swelling of the skin.75

In animal studies, a preparation containing 0.5% glabridin, one of the primary active constituents in licorice extract, prevented the redness and inflammation normally associated with UV exposure when pre-applied to the skin. Licorice extract also reduces melanin synthesis.74 Recent research suggests that UV-induced DNA damage and subsequent repair efforts precede melanin synthesis.11 Furthermore, licorice extract’s antioxidant activity has been shown to enhance the stability of other compounds when added to a topical dermatological cream.76 This antioxidant activity evidently protects skin against damage caused by free radical and reactive oxygen species.73

Rosemary (Rosmarinus officinalis), a fragrant evergreen perennial herb, has been used as a seasoning and medicinal herb for several millennia. Rosemary contains numerous beneficial compounds, including cancer-fighting chemicals, antioxidants, and anti-inflammatory agents.77-79 At least two of these, carnosic acid and ursolic acid, are especially beneficial to skin.80-82 Application of rosemary extract has been shown to prevent chemically induced skin tumors in a mouse model of human skin cancer. Depending on the concentration of the extract, tumors were inhibited by up to 99%.80

Rosemary (Rosmarinus Officinalis)

Earlier this year, French researchers demonstrated that ursolic acid, derived from rosemary, significantly inhibited the proliferation of melanoma cells in culture, apparently by promoting apoptosis (programmed cell death).82 More than a decade earlier, Rutgers University scientists demonstrated that in a mouse model of human skin cancer, both carnosic and ursolic acids markedly inhibit tumor growth when applied to the skin.80 Korean scientists have shown that “ursolic acid significantly suppressed the UVA-induced reactive oxygen species production and lipid peroxidation” in a human keratinocyte culture. They concluded that ursolic acid “may be useful in the prevention of UVA-induced photoaging.”83 In addition, research has demonstrated that when specially formulated with lipids, ursolic acid enhances the dermal collagen and ceramide content of normal human epidermal keratinocytes.84,85 Collagen provides the “skeleton” that gives shape and structure to the skin, while ceramide is a lipid that helps maintain proper immune function, as well as youthful moisture content, in the skin. Keratinocytes make up as much as 95% of epidermal tissues and are responsible for producing keratin, the tough protein that contributes to healthy hair, nails, and skin.

Conclusion

When it comes to protecting yourself against skin cancer, the most common of cancers worldwide, sunscreen agents such as zinc oxide alone may not be enough. While sunscreens can help shield against UV light-induced sunburn, it is crucial to also protect the skin against the free radicals generated by solar radiation. Left unchecked, these notoriously harmful agents may contribute to skin aging, DNA damage, and skin cancer.

Fortunately, a number of powerful plant-derived phytochemicals may help protect the skin via novel mechanisms that are distinct from those provided by sunscreen agents. Emerging evidence suggests that topically applied botanicals—including green tea, milk thistle, grape seed, turmeric root, licorice root, and rosemary—may prevent deleterious effects from sun exposure such as inflammation, DNA damage, immune deficits, skin aging, and cancer. The potent antioxidant properties of these plant extracts may account for their skin-protective actions.

The combination of sunscreen agents with botanical extracts may thus provide the most complete protection against the harmful effects of UV light, by both screening solar rays and preventing the formation of damaging free radicals. These combinations offer promise not only in helping to guard against skin cancers but also in promoting healthy, youthful skin.

References

1. Dennis LK, Beane Freeman LE, VanBeek MJ. Sunscreen use and the risk for melanoma: a quantitative review. Ann Int Med. 2003 Dec 16;139(12):966-78.

2. Haywood R, Wardman P, Sanders R, Linge C. Sunscreens inadequately protect against ultraviolet-A-induced free radicals in skin: implications for skin aging and melanoma? J Invest Dermatol. 2003 Oct;121(4):862-8.

3. Gasparro FP. Sunscreens, skin photobiology, and skin cancer: the need for UVA protection and evaluation of efficacy. Environ Health Perspect. 2000 Mar;108 Suppl 1:71-8.

4. Dangoisse C. Dermo-cosmetics and prevention of skin aging. Rev Med Brux. 2004 Sep;25(4):A365-70.

5. Greinert R, Volker B, Wende A, Voss S, Breitbart EW. Prevention of skin cancer. Necessity, implementation and success. Hautarzt. 2003 Dec;54(12):1152-63.

6. Schober-Flores C. The sun’s damaging effects. Dermatol Nurs. 2001 Aug;13(4):279-86.

7. Savona MR, Jacobsen MD, James R, Owen MD. Ultraviolet radiation and the risks of cutaneous malignant melanoma and non-melanoma skin cancer: perceptions and behaviours of Danish and American adolescents. Eur J Cancer Prev. 2005 Feb;14(1):57-62.

8. Available at: http://seer.cancer.gov/csr/1975_2001/results_merged/sect_16_melanoma.pdf. Accessed March 31, 2005.

9. Geller AC, Rutsch L, Kenausis K, Selzer P, Zhang Z. Can an hour or two of sun protection education keep the sunburn away? Evaluation of the Environmental Protection Agency’s Sunwise School Program. Environ Health. 2003 Nov 3;2(1):13.

10. Available at: http://www.cancer.org/docroot/CRI/content/CRI_2_4_1X_What_are_the_key_statistics_for_melanoma_50.asp?sitearea. Accessed March 31, 2005.

11. Agar N, Young AR. Melanogenesis: a photoprotective response to DNA damage? Mutat Res. 2005 Apr 1;571(1-2):121-32.

12. Mitchnick MA, Fairhurst D, Pinnell SR. Microfine zinc oxide (Z-cote) as a photostable UVA/UVB sunblock agent. J Am Acad Dermatol. 1999 Jan;40(1):85-90.

13. Wolf R, Matz H, Orion E, Lipozencic J. Sunscreens—the ultimate cosmetic. Acta Dermatovenerol Croat. 2003;11(3):158-62.

14. Prasad AS. Zinc: the biology and therapeutics of an ion. Ann Intern Med. 1996 Jul 15;125(2):142-4.

15. Kasperczyk S, Birkner E, Kasperczyk A, Zalejska-Fiolka J. Activity of superoxide dismutase and catalase in people protractedly exposed to lead compounds. Ann Agric Environ Med. 2004;11(2):291-6.

16. Kocaturk PA, Kavas GO, Erdeve O, Siklar Z. Superoxide dismutase activity and zinc and copper concentrations in growth retardation. Biol Trace Elem Res. 2004;102(1-3):51-9.

17. Tarnow P, Agren M, Steenfos H, Jansson JO. Topical zinc oxide treatment increases endogenous gene expression of insulin-like growth factor-1 in granulation tissue from porcine wounds. Scand J Plast Reconstr Surg Hand Surg. 1994 Dec;28(4):255-9.

18. Jin L, Murakami TH, Janjua NA, Hori Y. The effects of zinc oxide and diethyldithiocarbamate on the mitotic index of epidermal basal cells of mouse skin. Acta Med Okayama. 1994 Oct;48(5):231-6.

19. Diffey BL, Farr PM. Sunscreen protection against UVB, UVA and blue light: an in vivo and in vitro comparison. Br J Dermatol. 1991 Mar;124(3):258-63.

20. Farmer KC, Naylor MF. Sun exposure, sunscreens, and skin cancer prevention: a year-round concern. Ann Pharmacother. 1996 Jun;30(6):662-73.

21. Krekels G, Voorter C, Kuik F, et al. DNA protection by sunscreens: p53 immunostaining. Eur J Dermatol. 1997;7(4):259-62.

22. Meadows T. Effect of various sunscreen combinations on a product’s SPF value. J Soc Cosmet Chem. 1990 Mar-Apr;41:141-6.

23. Saladi RN, Persaud AN. The causes of skin cancer: A comprehensive review. Drugs Today (Barc.). 2005 Jan;41(1):37-53.

24. Diffey B. Sunscreen isn’t enough. J Photochem Photobiol B. 2001 Nov 15;64(2-3):105-8.

25. Bech-Thomsen N, Wulf HC. Sunbathers’ application of sunscreen is probably inadequate to obtain the sun protection factor assigned to the preparation. Photdermatol Photoimmunol Photomed. 1992-3 Dec;9(6):242-4.

26. Stokes R, Diffey B. How well are sunscreen users protected? Photodermatol Photoimmunol Photomed. 1997 Oct-Dec;13(5-6):186-8.

27. Phillips TJ, Bhawan J, Yaar M, Bello Y, Lopiccolo D, Nash JF. Effect of daily versus intermittent sunscreen application on solar simulated UV radiation-induced skin response in humans. J Am Acad Dermatol. 2000 Oct;43(4):610-8.

28. Calvo MS, Whiting SJ, Barton CN. Vitamin D intake: a global perspective of current status. J Nutr. 2005 Feb;135(2):310-6.

29. Calvo MS, Whiting SJ, Barton CN. Vitamin D fortification in the United States and Canada: current status and data needs. Am J Clin Nutr. 2004 Dec;80(6 Suppl):1710S-6S.

30. Egan KM, Sosman JA, Blot WJ. Sunlight and reduced risk of cancer: is the real story vitamin D? J Natl Cancer Inst. 2005 Feb 2;97(3):161-3.

31. Reichrath J, Girndt M, Tilgen W, Querings K. UV-exposition and vitamin-D: How much sunlight do we need? Exp Dermatol. 2005 Feb;14(2):153.

32. Berwick M, Armstrong BK, Ben Porat L, et al. Sun exposure and mortality from melanoma. J Natl Cancer Inst. 2005 Feb 2;97(3):195-9.

33. Holick MF. Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease. Am J Clin Nutr. 2004 Dec;80(6 Suppl):1678S-88S.

34. Miyako K, Kinjo S, Kohno H. Vitamin D deficiency rickets caused by improper lifestyle in Japanese children. Pediatr Int. 2005 Apr;47(2):142-6.

35. Strickland FM, Kuchel JM, Halliday GM. Natural products as aids for protecting the skin’s immune system against UV damage. Cutis. 2004 Nov;74(5 Suppl):24-8.

36. Katiyar SK, Elmets CA. Green tea polyphenolic antioxidants and skin photoprotection (review). Int J Oncol. 2001 Jun;18(6):1307-13.

37. Morley N, Clifford T, Salter L, et al. The green tea polyphenol (-)-epigallocatechin gallate and green tea can protect human cellular DNA from ultraviolet and visible radiation-induced damage. Photodermatol Photoimmunol Photomed. 2005 Feb;21(1):15-22.

38. Katiyar SK. Skin photoprotection by green tea: antioxidant and immunomodulatory effects. Curr Drug Targets Immune Endocr Metabol Disord. 2003 Sep;3(3):234-42.

39. Vayalil PK, Mittal A, Hara Y, Elmets CA, Katiyar SK. Green tea polyphenols prevent ultraviolet light-induced oxidative damage and matrix metalloproteinases expression in mouse skin. J Invest Dermatol. 2004 Jun;122(6):1480-7.

40. Katiyar SK, Mukhtar H. Green tea polyphenol (-)-epigallocatechin-3-gallate treatment to mouse skin prevents UVB-induced infiltration of leukocytes, depletion of antigen-presenting cells, and oxidative stress. J Leukoc Biol. 2001 May;69(5):719-26.

41. Vayalil PK, Elmets CA, Katiyar SK. Treatment of green tea polyphenols in hydrophilic cream prevents UVB-induced oxidation of lipids and proteins, depletion of antioxidant enzymes and phosphorylation of MAPK proteins in SKH-1 hairless mouse skin. Carcinogenesis. 2003 May;24(5):927-36.

42. Mittal A, Piyathilake C, Hara Y, Katiyar SK. Exceptionally high protection of photocarcinogenesis by topical application of (-)-epigallocatechin-3-gallate in hydrophilic cream in SKH-1 hairless mouse model: relationship to inhibition of UVB-induced global DNA hypomethylation. Neoplasia. 2003 Nov;5(6):555-65.

43. Elmets CA, Singh D, Tubesing K, et al. Cutaneous photoprotection from ultraviolet injury by green tea polyphenols. J Am Acad Dermatol. 2001 Mar;44(3):425-32.

44. Katiyar SK, Afaq F, Perez A, Mukhtar H. Green tea polyphenol (-)-epigallocatechin-3-gallate treatment of human skin inhibits ultraviolet radiation-induced oxidative stress. Carcinogenesis. 2001 Feb;22(2):287-94.

45. Katiyar SK, Bergamo BM, Vyalil PK, Elmets CA. Green tea polyphenols: DNA photodamage and photoimmunology. J Photochem Photobiol B. 2001 Dec 31;65(2-3):109-14.

46. Lu YP, Lou YR, Xie JG, et al. Topical applications of caffeine or (-)-epigallocatechin gallate (EGCG) inhibit carcinogenesis and selectively increase apoptosis in UVB-induced skin tumors in mice. Proc Natl Acad Sci USA. 2002 Sep 17;99(19):12455-60.

47. Chung JH, Han JH, Hwang EJ, et al. Dual mechanisms of green tea extract (EGCG)-induced cell survival in human epidermal keratinocytes. FASEB J. 2003 Oct;17(13):1913-5.

48. Katiyar SK. Silymarin and skin cancer prevention: anti-inflammatory, antioxidant and immunomodulatory effects (review). Int J Oncol. 2005 Jan;26(1):169-76.

49. Lahiri-Chatterjee M, Katiyar SK, Mohan RR, Agarwal R. A flavonoid antioxidant, silymarin, affords exceptionally high protection against tumor promotion in the SENCAR mouse skin tumorigenesis model. Cancer Res. 1999 Feb 1;59(3):622-32.

50. Katiyar SK, Roy AM, Baliga MS. Silymarin induces apoptosis primarily through a p53-dependent pathway involving Bcl-2/Bax, cytochrome c release, and caspase activation. Mol Cancer Ther. 2005 Feb;4(2):207-16.

51. Singh RP, Dhanalakshmi S, Agarwal C, Agarwal R. Silibinin strongly inhibits growth and survival of human endothelial cells via cell cycle arrest and downregulation of survivin, Akt and NF-kappaB: implications for angioprevention and antiangiogenic therapy. Oncogene. 2005 Feb 10;24(7):1188-202.

52. Mallikarjuna G, Dhanalakshmi S, Singh RP, Agarwal C, Agarwal R. Silibinin protects against photocarcinogenesis via modulation of cell cycle regulators, mitogen-activated protein kinases, and Akt signaling. Cancer Res. 2004 Sep 1;64(17):6349-56.

53. Li LH, Wu LJ, Zhou B, et al. Silymarin prevents UV irradiation-induced A375-S2 cell apoptosis. Biol Pharm Bull. 2004 Jul;27(7):1031-36.

54. Dhanalakshmi S, Mallikarjuna GU, Singh RP, Agarwal R. Dual efficacy of silibinin in protecting or enhancing ultraviolet B radiation-caused apoptosis in HaCaT human immortalized keratinocytes. Carcinogenesis. 2004 Jan;25(1):99-106.

55. Singh RP, Agarwal R. Flavonoid antioxidant silymarin and skin cancer. Antioxid Redox Signal. 2002 Aug;4(4):655-63.

56. Singh RP, Tyagi AK, Zhao J, Agarwal R. Silymarin inhibits growth and causes regression of established skin tumors in SENCAR mice via modulation of mitogen-activated protein kinases and induction of apoptosis. Carcinogenesis. 2002 Mar;23(3):499-510.

57. Bhatia N, Agarwal C, Agarwal R. Differential responses of skin cancer-chemopreventive agents silibinin, quercetin, and epigallocatechin 3-gallate on mitogenic signaling and cell cycle regulators in human epidermoid carcinoma A431 cells. Nutr Cancer. 2001;39(2):292-9.

58. Singh RP, Agarwal R. A cancer chemopreventive agent, silibinin targets mitogenic and survival signaling in prostate cancer. Mutat Res. 2004 Nov 2;555(1-2):21-32.

59. Chu SC, Chiou HL, Chen PN, Yang SF, Hsieh YS. Silibinin inhibits the invasion of human lung cancer cells via decreased productions of urokinase-plasminogen activator and matrix metalloproteinase-2. Mol Carcinog. 2004 Jul;40(3):143-9.

60. Tyagi A, Agarwal C, Harrison G, Glode LM, Agarwal R. Silibinin causes cell cycle arrest and apoptosis in human bladder transitional cell carcinoma cells by regulating CDKI-CDK-cyclin cascade, and caspase 3 and PARP cleavages. Carcinogenesis. 2004 Sep;25(9):1711-20.

61. Bauer JH, Goupil S, Garber GB, Helfand SL. An accelerated assay for the identification of lifespan-extending interventions in Drosophila melanogaster. Proc Natl Acad Sci USA. 2004 Aug 31;101(35):12980-5.

62. Borra MT, Smith BC, Denu JM. Mechanism of human SIRT1 activation by resveratrol. J Biol Chem. 2005 Mar 4.

63. Douillet-Breuil AC, Jeandet P, Adrian M, Bessis R. Changes in the phytoalexin content of various Vitis spp. in response to ultraviolet C elicitation. J Agric Food Chem. 1999 Oct;47(10):4456-61.

64. Roy AM, Baliga MS, Elmets CA, Katiyar SK. Grape seed proanthocyanidins induce apoptosis through p53, Bax, and caspase 3 pathways. Neoplasia. 2005 Jan;7(1):24-36.

65. Mittal A, Elmets CA, Katiyar SK. Dietary feeding of proanthocyanidins from grape seeds prevents photocarcinogenesis in SKH-1 hairless mice: relationship to decreased fat and lipid peroxidation. Carcinogenesis. 2003 Aug;24(8):1379-88.

66. Zhao J, Wang J, Chen Y, Agarwal R. Anti-tumor-promoting activity of a polyphenolic fraction isolated from grape seeds in the mouse skin two-stage initiation-promotion protocol and identification of procyanidin B5-3’-gallate as the most effective antioxidant constituent. Carcinogenesis. 1999 Sep;20(9):1737-45.

67. Shi J, Yu J, Pohorly JE, Kakuda Y. Polyphenolics in grape seeds-biochemistry and functionality. J Med Food. 2003;6(4):291-9.

68. Phan TT, See P, Lee ST, Chan SY. Protective effects of curcumin against oxidative damage on skin cells in vitro: its implication for wound healing. J Trauma. 2001 Nov;51(5):927-31.

69. Huang MT, Newmark HL, Frenkel K. Inhibitory effects of curcumin on tumorigenesis in mice. J Cell Biochem Suppl. 1997;27:26-34.

70. Research Report #786, Sabinsa Corporation, 1998.

71. Research Report, Sami Labs Ltd, 2002.

72. Research Report, Sabinsa Corporation, 2003

73. Di Mambro VM, Fonseca MJ. Assays of physical stability and antioxidant activity of a topical formulation added with different plant extracts. J Pharm Biomed Anal. 2005 Feb 23;37(2):287-95.

74. Yokota T, Nishio H, Kubota Y, Mizoguchi M. The inhibitory effect of glabridin from licorice extracts on melanogenesis and inflammation. Pigment Cell Res. 1998 Dec;11(6):355-61.

75. Saeedi M, Morteza-Semnani K, Ghoreishi MR. The treatment of atopic dermatitis with licorice gel. J Dermatolog Treat. 2003 Sep;14(3):153-7.

76. Morteza-Semnani K, Saeedi M, Shahnavaz B. Comparison of antioxidant activity of extract from roots of licorice (Glycyrrhiza glabra L.) to commercial antioxidants in 2% hydroquinone cream. J Cosmet Sci. 2003 Nov;54(6):551-8.

77. Ho CT, Wang M, Wei GJ, Huang TC, Huang MT. Chemistry and antioxidative factors in rosemary and sage. Biofactors. 2000;13(1-4):161-6.

78. Calabrese V, Scapagnini G, Catalano C, et al. Biochemical studies of a natural antioxidant isolated from rosemary and its application in cosmetic dermatology. Int J Tissue React. 2000;22(1):5-13.

79. Baricevic D, Sosa S, Della LR et al. Topical anti-inflammatory activity of Salvia officinalis L. leaves: the relevance of ursolic acid. J Ethnopharmacol. 2001 May;75(2-3):125-32.

80. Huang MT, Ho CT, Wang ZY, et al. Inhibition of skin tumorigenesis by rosemary and its constituents carnosol and ursolic acid. Cancer Res. 1994 Feb 1;54(3):701-8.

81. Offord EA, Gautier JC, Avanti O, et al. Photoprotective potential of lycopene, beta-carotene, vitamin E, vitamin C and carnosic acid in UVA-irradiated human skin fibroblasts. Free Radic Biol Med . 2002 Jun 15;32(12):1293-303.

82. Harmand PO, Duval R, Delage C, Simon A. Ursolic acid induces apoptosis through mitochondrial intrinsic pathway and caspase-3 activation in M4Beu melanoma cells. Int J Cancer. 2005 Mar 10;114(1):1-11.

83. Soo LY, Jin DQ, Beak SM, Lee ES, Kim JA. Inhibition of ultraviolet-A-modulated signaling pathways by asiatic acid and ursolic acid in HaCaT human keratinocytes. Eur J Pharmacol. 2003 Aug 29;476(3):173-8.

84. Both DM, Goodtzova K, Yarosh DB, Brown DA. Liposome-encapsulated ursolic acid increases ceramides and collagen in human skin cells. Arch Dermatol Res. 2002 Jan;293(11):569-75.

85. Yarosh DB, Both D, Brown D. Liposomal ursolic acid (merotaine) increases ceramides and collagen in human skin. Horm Res. 2000;54(5-6):318-21.

Subscribe to Life Extension Magazine®

Subscribe Now

Advertise in Life Extension Magazine®

Learn More