R. Bissonnette, MD, FRCPC
Innovaderm Research, Montreal, QC, Canada
Sunscreens have been around for more than 70 years. Designed originally to protect against sunburn, recognition of the various harmful effects of ultraviolet (UV) radiation has broadened the use of sunscreens. The addition of effective UVA sunscreen agents has enabled claims beyond protection against sunburn to include prevention of idiopathic photodermatosis, actinic keratoses, skin cancer, and photoaging. This article will review some of the recent advances in photoprotection, including the development of sunscreen formulations offering higher and broader protection against solar radiation.
sunscreens, photoprotection, ultraviolet A, ultraviolet B, UVA, UVB, sun protection factor, SPF
Protection Against Ultraviolet A (UVA) Radiation
Rating UVA Protection
The almost universal use of the sun protection factor (SPF) has lured many consumers into thinking that a higher SPF means a better sunscreen. Because SPF is mostly an indicator of UVB protection, it is difficult for consumers and physicians to compare the UVA protection afforded by sunscreens.1 For many years, some countries have been using UVA labeling systems that can provide guidance on both UVA and UVB protection that is offered by sunscreens. Other countries, like the US and Canada, have been slower to introduce guidelines for UVA protection labeling.
Modifications to Sunscreen Labeling
The US FDA recently proposed inclusion of a 4 star grading system in conjunction with a descriptor (i.e., low, medium, high, and highest) to rate UVA protection.2 This star rating system will depend on results of both in vitro and in vivo UVA testing. According to the agency, UVA ratings would be based on 2 tests: one would measure the sunscreen’s ability to reduce UVA penetration and the second would measure the product’s ability to prevent tanning. The test that yields the lowest level of UVA protection would determine the number of stars that the sunscreen would receive. This will help consumers and physicians identify the level of UVA protection provided by the different sunscreens. Other modifications include making minor changes to UVB testing procedures to improve accuracy, increasing the maximum sunburn protection factor from SPF 30+ to SPF 50+, and sanctioning the use of new combinations of active ingredients.2
Avobenzone and Photostability
Protection against UVA radiation was revolutionized by the introduction of butyl methoxydibenzoylmethane (avobenzone) in the late 1980s and early 1990s. This was the first organic sunscreen agent that provided some protection for mid- to long-range UVA rays. However, the degradation of some UVA filters, such as avobenzone, by sunlight, prompted the need to stabilize the formulation in order to prevent the loss of efficacy. Upon absorption of UV radiation, the avobenzone molecule can transform into a molecule that no longer absorbs UVA radiation. In formulations where avobenzone is not photostable, UVA protection decreases with the time spent under the sun. This has been shown to occur after as little as 60-90 minutes of sun exposure.3
A number of different companies have developed systems to stabilize avobenzone in the final formulations. For example, a combination of avobenzone and 2-ethylhexyl ester (octocrylene) has been shown to achieve a photostable product.4 The addition of diethylhexyl 2,6-naphthalate also makes avobenzone photostable.5 The combination of diethylhexyl 2,6-naphthalatate, avobenzone and oxybenzone is known under the commercial name of Helioplex™ and it is present in UltraSheer® and Age Shield® sunscreens (Neutrogena®/Johnson & Johnson). The addition of
Tinosorb S® (Ciba Specialty Chemicals) has also been shown to photostabilize avobenzone.6 Confirmation of avobenzone’s photostability in a given formulation is difficult unless the sunscreen’s chemical stability has been studied and the results are published in a peer reviewed journal. In the absence of such studies, physicians can get indirect evidence of the photostability of a given formulation from UVA protection factor determination with methods such as persistent pigment darkening (PPD).
PPD evaluates pigmentation present at 2 hours after the end of exposure to different UVA fluences. Because UVA exposures for these methods are rather lengthy, a sunscreen formulation with unstable avobenzone will have a lower protection factor than a similar formulation with stabilized avobenzone.
Recently Introduced Organic UVA Sunscreen Agents
A number of UVA sunscreen agents have been introduced in the past few years. Unfortunately, their availability varies widely from country to country. For example, in the US and Canada, sunscreen agents are considered to be drugs. Sunscreen manufacturers must therefore submit a new drug application when they want to incorporate a new agent into a formulation. This explains why ecamsule (terephthalylidene dicamphor sulphonic acid [Mexoryl SX™, L’Oréal]) was only recently introduced in the US in 2006, whereas, this agent has been available in most other regions of the globe for more than 10 years. Mexoryl SX™ is a photostable chemical sunscreen agent that offers mid-range UVA protection.7 When combined with avobenzone, UVA protection is enhanced. Sunscreen products that contain Mexoryl SX™, and are available in the US, include Anthelios SX™ Daily Moisturizing Cream (SPF 15), Anthelios™ 15 Sunscreen Cream (SPF 15) and Anthelios SX™ 40 Sunscreen Cream (SPF 40, to be introduced in 2008).
Dometrizole trisiloxane (Mexoryl XL™) is another recently introduced organic sunscreen agent offering mid-range UVA protection. The addition of Mexoryl XL™ to Mexoryl SX™ has been shown to increase UVA protection in a synergistic manner, which may be attributable to its 2 phase component. Mexoryl XL™ was introduced in Canada in 2006. It has not yet been approved in the US, but has been available worldwide for many years in different sunscreens made by L’Oréal. In Canada, Mexoryl XL™ can be found in sunscreens sold under different brands including Anthelios™, Ombrelle™, Vichy™ and Biotherm™ (L’Oréal).
Bemotrizinol and bisoctrizole (Tinosorb S® and Tinosorb M®
respectively, Ciba Specialty Chemicals) are organic compounds that also provide broad-spectrum UV protection. Tinosorb S® has been shown to increase photostability of avobenzone.6 Tinosorb S® and Tinosorb M® are mid-range photostable sunscreen agents that have been used in Europe for many years, but they are not yet approved in the US. These UV filters have recently been introduced in Canada and are formulated in Minesol® SPF 60 products (RoC®/Johnson & Johnson).
Protection Against Visible Light
The effect of visible light on the skin has received very little attention, compared with UV radiation. The role of visible light, viewed as both physiologic and pathologic phenomena, and its effects on the skin are probably less important than the role of UV radiation. However, visible light sensitivity is an important phenomenon in diseases such as porphyria, solar urticaria, and other idiopathic photodermatoses, such as polymorphous light eruption. Patients who undergo photodynamic therapy treatments also become sensitive to visible light for a few days because of the accompanying topical medications, such as aminolevulinic acid and methylaminolevulinate, or for a few weeks due to systemic agents like porfimer sodium. A recent study by Mahmoud, et al. suggested that visible light exposure can increase pigmentation in patients with skin phototype IV to VI.8 Protection against visible light might be important for darker skinned patients who have pigmentary disorders such as post-inflammatory hyperpigmentation and melasma. Further research on the effects of visible light is definitely needed.
Organic sunscreen agents usually offer no protection against visible light, as their absorption spectrum is limited to UVB and UVA wavebands. Inorganic sunscreen agents, such as iron oxide, titanium dioxide, and zinc oxide can offer some visible light protection. However, the spectral protection of these agents varies according to their particle size. Larger particles of titanium dioxide and zinc oxide can protect in the visible range. Earlier formulations containing physical blocking agents tended to leave a white/pasty film on the skin, but with the advent of smaller-sized particles, modern physical sunscreens have made improvements in their effect on cosmetic appearance. Iron oxide is another physical UV blocking agent; however, it has the unique advantage of being closer to the natural skin color of phototype II and III individuals. The difference in visible light protection afforded by high SPF sunscreens with inorganic sunscreen agents was illustrated in a recent study that compared 2 inorganic sunscreens containing titanium dioxide, zinc oxide, and iron oxide for their ability to protect against blue light sensitivity induced by aminolevulinic acid application.9 The sunscreen containing 3.2% iron oxide (Avène Compact, Pierre Fabre Dermo-Cosmétique) offered a protection factor of 22:1 (i.e., the ratio of the lower blue light fluence that induced erythema on sunscreen protected skin to the lower blue light fluence that induced erythema on skin that was unprotected). Whereas the sunscreen with a lower concentration of 0.3% iron oxide offered only a protection factor of 2:1.
Systemic Absorption of Sunscreening Agents
Until recently, systemic exposure to sunscreen agents had also received relatively little attention in the medical literature. Agents such as benzophenones and octyl-methoxycinnamate can be detected in plasma and urine after topical application of sunscreen products.10 Unfortunately, most of these studies were conducted with non-commercial sunscreen formulations or were performed at significantly higher doses than what the average consumer uses. Additional research is definitely needed to explore the absorption of active agents contained in commercial sunscreens used under normal conditions. Furthermore, studies assessing the risks (or benefits) of systemic absorption of various sunscreen agents in adults, children, and pregnant women are also warranted.
Sunlight, Vitamin D and Sunscreens
Over the past few years there has been considerable media coverage about the influence of vitamin D and sun exposure on various diseases, including different types of cancer. The incidence of and mortality from many cancers have been reported to be reduced with decreasing latitude.11 Holick hypothesized that this reduction is related to higher vitamin D production from increased sun exposure.11 Vitamin D synthesis is a UVB phenomenon and sunscreens are usually very effective in protecting against UVB. Few prospective studies on the role of vitamin D and sun exposure in cancer prevention have been published. Additional studies are necessary to address issues such as the optimal amount of vitamin D needed to have beneficial effects and the role of oral vitamin D intake versus vitamin D synthesis following sun exposure.
Sun avoidance and the adequate use of high SPF and high UVA protection sunscreens on all exposed skin areas may still be appropriate for a kidney transplant patient who already has had multiple invasive squamous cell carcinomas. However, the situation is different for a healthy phototype IV indoor worker living in Canada who has no personal or familial history of skin cancer and takes part in no outdoor activities. Based on the current retrospective and prospective studies, physicians should individualize the sun protection advice that they give to their patients and discuss whether additional benefits can be derived from oral vitamin D supplementation. The Canadian Cancer Society issued a statement in 2007 recommending that Canadian adults should consider taking 1000 IU of vitamin D daily. This was based on evidence suggesting that vitamin D could reduce the risks of breast, colorectal, and prostate cancers.
Many sunscreens now offer very good broad-spectrum protection in both the UVA and UVB ranges. In many countries, changes in labeling guidelines will make it easier for consumers and physicians to evaluate the level of UVA protection afforded by sunscreens. However, further research is needed in many areas including the role of visible light, the risks of systemic absorption of sunscreen agents, and the role of vitamin D and sun exposure in preventing cancers and other diseases.
- Bissonnette R, Allas S, Moyal D, et al. Comparison of UVA protection afforded by high sun protection factor sunscreens. J Am Acad Dermatol 43(6):1036-8 (2000 Dec).
- Department of Health and Human Services, Food and Drug Administration. Federal Register, 21 CRF Parts 347 and 353 Sunscreen Drug Products for Over-the-Counter Human Use; Proposed Amendment of Final Monograph; Proposed Rule. Vol. 72, No. 165 (2007 August 27).
- Gonzalez H, Tarras-Wahlberg N, Stromdahl B, et al. Photostability of commercial sunscreens upon sun exposure and irradiation by ultraviolet lamps. BMC Dermatol 7:1 (2007).
- Gaspar LR, Maia Campos PM. Evaluation of the photostability of different UV filter combinations in a sunscreen. Int J Pharm 307(2):123-8 (2006 Jan 13).
- Cole C, Chu M, Finkey MB, et al. Comparison of photoprotection efficacy and photostability of broad spectrum sunscreens. Presented at: The 64th Annual Meeting of the American Academy of Dermatology; San Francisco, CA; March 3-7, 2006. Poster #P2617.
- Chatelain E, Gabard B. Photostabilization of butyl methoxydibenzoylmethane (Avobenzone) and ethylhexyl methoxycinnamate by bis-ethylhexyloxyphenol methoxyphenyl triazine (Tinosorb S), a new UV broadband filter. Photochem Photobiol 74(3):401-6 (2001 Sep).
- Moyal D. Prevention of ultraviolet-induced skin pigmentation. Photodermatol Photoimmunol Photomed 2004;20(5):243-7 (2004 Oct).
- Mahmoud BH, Hexsel C, Lim H, et al. Impact of long wavelength UVA and visible light on melanocompetent skin. Presented at: The 66th Annual Meeting of the American Academy of Dermatology; San Antonio, TX; February 1-5, 2008. Poster #P2420.
- Bissonnette R, Nigen S, Bolduc C, et al. Protection afforded by sunscreens containing inorganic sunscreening agents against blue light sensitivity induced by aminolevulinic acid. Dermatol Surg. In press 2008.
- Janjua NR, Kongshoj B, Andersson AM, et al. Sunscreens in human plasma and urine after repeated whole-body topical application. J Eur Acad Dermatol Venereol 22(4):456-61 (2008 Apr).
- Holick MF. Vitamin D deficiency. N Engl J Med 357(3):266-81 (2007 Jul 19).