Potential health risks of sunscreen

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Sunscreen is widely acknowledged to protect against sunburn and two common forms of skin cancer, squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). However, there is some evidence that sunscreen use can contribute to negative health outcomes. The major claims include:

These issues have precipitated various levels of disagreement within the academic community over the benefits and risks of sunscreen use. Most health authorities and medical associations have concluded that, on the whole, sunscreen use is beneficial.[1]

Studies of melanoma rates[edit]

Malignant melanoma has been found more frequently in sunscreen users compared to non-users in some studies.[2] Other studies found fair skinned people used more suncreen and had more skin cancer, but did not address cause and effect.[3][4][5][6][7][8] A meta-analysis of 9067 patients from 11 case–control studies found no association between sunscreen use and development of malignant melanoma. It was suggested that sunscreens block the natural warnings and adaptations mediated by UVB, but allow damage from UVA to go unchecked.[9]

However, these claims could not be supported in three meta-analyses.[10][11] (Huncharek and Kupelnick, 2000, Annals Epidemiol. vol. 10, p. 467.)

The only evidence suggesting a relationship between sunscreen and melanoma is correlational, and thus cannot be used to establish a causal relationship.

Even though it is rare, malignant melanoma is responsible for 75% of all skin cancer-related death cases, making it the most lethal form of skin cancer.[12][13] Many scientists argue that the sun-avoiding health message does increase some forms of skin cancer.[14]

There is a correlation between high UV exposure, especially during childhood, and the risk to develop melanoma,[15][16][17] resulting in a WHO recommendation for persons under 18 to avoid sunbeds.[18]

Alternative view[edit]

Authors who claim that sunscreen use causes melanoma have speculated that this occurs by one of the following mechanisms:

  • the absence of UVA filters combined with a longer exposure time of the sunscreen user[3][19][20][21]
  • By reducing the exposure of the skin to UVB radiation, sunscreen suppresses the skin's production of the natural photoprotectant, melanin,[22] and the lack of melanin leads to an increased risk of melanoma.[3]
  • free radical generation by sunscreen chemicals that have penetrated into the skin.[23][24][25][26][27]
  • pathogenic cytotoxicity and carcinogenicity of micronized titanium[28] or zinc oxide[citation needed] nanoparticles.
  • Retinyl palmitate, a form of Vitamin A that is an ingredient in some sunscreens, may encourage tumor growth in animals.[29] Diisopropyl adipate and retinoic acid have also demonstrated carcinogenic effects in mice.[30]

Sunscreen ingredients can damage DNA[edit]

Some sunscreen ingredients may damage cells when illuminated.[31][32][33][34] PABA causes DNA damage in human cells.[35] PABA was banned as a sunscreen ingredient several years after these findings were published. Phenylbenzimidazole (PBI) causes DNA photodamage when illuminated while in contact with bacteria or human keratinocytes.[27][36][37]

Some sunscreen ingredients generate reactive oxygen species (ROS) when exposed to UVA,[38] which can increase carbonyl formation in albumin[39] and damage DNA. It is also well known that DNA alterations are necessary for cancer to occur.

Many sunscreen ingredients generate singlet oxygen under illumination.[40] Several popular UV-filters have been demonstrated to generate free radicals.[39]

Kerry Hanson, et al. have shown for the three sunscreen ingredients octocrylene, octylmethoxycinnamate, and benzophenone-3 that after the sunscreen chemicals had time to absorb into the skin the number of ROS and free radicals is higher for the sunscreen user than for the non-user.[26] Such an increase in ROS might increase the chance of melanoma, but this hypothesis has not been tested.

Studies have found that titanium dioxide nanoparticles cause genetic damage in mice, suggesting that humans may be at risk of cancer or genetic disorders resulting from exposure.[41] Nanoparticles are commonly used in American sunscreens to make them transparent on the skin; the EU has treated these with more caution, demanding they be treated like new chemicals, subject to safety assessments before being deployed in consumer products. In 2009, the EU initiated labelling requirements for nanoparticle ingredients in certain sunscreens and cosmetics. [42]

DNA, in particular, is susceptible to damage caused by photo-excited compounds.[36]

Sunscreen ingredients penetrate the skin[edit]

Between 1% and 10% of some[clarification needed] sunscreen ingredients are absorbed into the body through the skin.[23][25][43][44][45][46][47][48][49]

The absorption of the sunscreen ingredients into the skin does not occur instantaneously, but the sunscreen concentration in the deeper levels of the skin increases over time.[26] For this reason the amount of time between the topical application of sunscreen and the end of the illumination period is an important parameter in experimental studies. Illumination of those sunscreen chromophores which have penetrated the stratum corneum amplifies the generation of ROS.[26]

Animal experiments[edit]

Wolf et al. found that sunscreens failed to protect against UV-A radiation induced increase in melanoma incidence in mice[50] while 3 other studies have found that sunscreen delays or prevents the formation of actinic keratoses and carcinomas, but not melanoma.[51][52][53]

Clinical study[edit]

In 2008, a clinical study showed that the application of sunscreen prevents squamous cell carcinoma, basal cell carcinoma, and actinic keratosis. The study included 60 transplant patients who received immunosuppression, a group of persons with a particularly high risk to develop skin cancer. The patients were very compliant, using sunscreen 5.6 days per week on average. The control group was recruited retrospectively and consisted of 60 transplant patients equally matched for age, skin type and kind of transplant organ. The control group had been instructed to use sunscreen as well, but were not provided with cost-free sunscreen and showed very poor compliance.

After 24 months, the sunscreen group showed a 53% reduction of actinic keratosis, while the control group showed an increase of 38%. The difference in the development of SCC and BCC were also highly significant. Non-significant results included a slight decrease of herpes and warts and a slight increase in acne in the sunscreen group.[54][55]

In 2011, Australian researchers found that the regular application of sunscreen with a sun protection factor of 15 or more during a 5-year treatment period reduced the incidence of new primary melanomas during a subsequent 10-year follow-up period.[56] However an accompanying editorial found the statistics unconvincing.[57] In May 2011 the same journal (Journal of Clinical Oncology) published an editorial by Michael A. Goldenhersh and Meni Koslowsky entitled Increased Melanoma After Regular Sunscreen Use? which found that the areas of the skin which had been treated with sunscreen had non-significantly more melanomas than the untreated controls.[58]

Social impact[edit]

Lawsuits have been filed against sunscreen manufacturers.[59] In 2006, a number of class-action lawsuits alleged that sunscreen manufacturers misled consumers into believing that these products provided full sun protection. The lawsuits were settled in 2009.[60]

These lawsuits limit themselves to the absence of UV-A filters.

In August 2007, the United States Food and Drug Administration tentatively concluded that "the available evidence fails to show that sunscreen use alone prevents skin cancer[...]"[61]

Sunscreen ingredients are not tested in Europe, Japan or Australia for photocarcinogenic effects before being introduced to the market. In the US, most sunscreens sold in 2008 have not passed regulatory testing either, due to a grandfather clause. Three new sunscreen active ingredients introduced in the US since 1978 have fulfilled new testing requirements.[62]

Sunscreen and vitamin D[edit]

The use of sunscreen with a sun protection factor (SPF) of 8 inhibits more than 95% of vitamin D production in the skin.[63][64] A recent study has shown that more Australians and New Zealanders are vitamin D deficient than previously thought.[65] Ironically, there are indications that vitamin D deficiency may lead to skin cancer.[66] To avoid vitamin D deficiency, vitamin supplements can be taken. Adequate amounts of vitamin D3 can be made in the skin after only ten to fifteen minutes of sun exposure at least two times per week to the face, arms, hands, or back without sunscreen in white people (those with darker skins require up to six times longer in the sun). This applies in sunlight when the UV index is greater than 3, which occurs daily within the tropics and during the spring and summer seasons in temperate regions. With sunscreen, the required exposure would be longer: if 95% of vitamin D production is inhibited, then it proceeds at only 5%, or 1/20th, the normal rate, and it would take 20 times as long—200 to 300 minutes (3-1/3 to 5 hours), twice a week—of sun exposure to the face, arms, hands, or back for adequate vitamin D to be made in the skin. Obviously, the required time would decrease with increased body exposure area, as when wearing a swimsuit on a beach, a very common setting where sunscreen is used. By this math, it is apparent that vacationers who spend hours on the beach each day with sunscreen on may make more vitamin D in a week of vacation than they do during a typical week in their lives with no sunscreen, if they spend most of their non-vacationing time inside houses, offices, and other buildings where they get almost no sun exposure. Also, it is worth noting that with longer exposure to UVB rays, equilibrium is achieved in the skin, and the vitamin simply degrades as fast as it is generated. Vitamin D overdose is nearly impossible from natural sources, including food sources.[citation needed]

See also[edit]

References[edit]

  1. ^ Moloney FJ, Collins S, Murphy GM (2002). "Sunscreens: safety, efficacy and appropriate use". Am J Clin Dermatol 3 (3): 185–91. PMID 11978139. 
  2. ^ Westerdahl J, Ingvar C, Mâsbäck A, Olsson H (July 2000). "Sunscreen use and malignant melanoma". Int. J. Cancer 87 (1): 145–50. doi:10.1002/1097-0215(20000701)87:1<145::AID-IJC22>3.0.CO;2-3. PMID 10861466. 
  3. ^ a b c Autier P; Dore J F; Schifflers E; et al. (1995). "Melanoma and use of sunscreens: An EORTC case control study in Germany, Belgium and France". Int. J. Cancer 61 (6): 749–755. doi:10.1002/ijc.2910610602. PMID 7790106. 
  4. ^ Weinstock, M. A. (1999). "Do sunscreens increase or decrease melanoma risk: An epidemiologic evaluation". Journal of Investigative Dermatology Symposium Proceedings 4 (1): 97–100. doi:10.1038/sj.jidsp. PMID 10537017. 
  5. ^ Vainio H, Bianchini F (December 2000). "Cancer-preventive effects of sunscreens are uncertain". Scand J Work Environ Health 26 (6): 529–31. PMID 11201401. 
  6. ^ Wolf P, Quehenberger F, Müllegger R, Stranz B, Kerl H. (1998). "Phenotypic markers, sunlight-related factors and sunscreen use in patients with cutaneous melanoma: an Austrian case-control study". Melanoma Res. 8 (4): 370–378. doi:10.1097/00008390-199808000-00012. PMID 9764814. 
  7. ^ Graham S, Marshall J, Haughey B, et al. (October 1985). "An inquiry into the epidemiology of melanoma". Am. J. Epidemiol. 122 (4): 606–19. PMID 4025303. 
  8. ^ Beitner H, Norell SE, Ringborg U, Wennersten G, Mattson B. (1990). "Malignant melanoma: aetiological importance of individual pigmentation and sun exposure". Br J Dermatol. 122 (1): 43–51. doi:10.1111/j.1365-2133.1990.tb08238.x. PMID 2297503. 
  9. ^ Garland C, Garland F, Gorham E (1992). "Could sunscreens increase melanoma risk?". Am J Public Health 82 (4): 614–5. doi:10.2105/AJPH.82.4.614. PMC 1694089. PMID 1546792. 
  10. ^ Huncharek M, Kupelnick B (July 2002). "Use of topical sunscreens and the risk of malignant melanoma: a meta-analysis of 9067 patients from 11 case-control studies". Am J Public Health 92 (7): 1173–7. doi:10.2105/AJPH.92.7.1173. PMC 1447210. PMID 12084704. 
  11. ^ Dennis LK, Beane Freeman LE, VanBeek MJ (December 2003). "Sunscreen use and the risk for melanoma: a quantitative review". Ann. Intern. Med. 139 (12): 966–78. PMID 14678916. 
  12. ^ Jerant AF, Johnson JT, Sheridan CD, Caffrey TJ (July 2000). "Early detection and treatment of skin cancer". Am Fam Physician 62 (2): 357–68, 375–6, 381–2. PMID 10929700. 
  13. ^ Boring CC, Squires TS, Tong T (1991). "Cancer statistics, 1991". CA Cancer J Clin 41 (1): 19–36. doi:10.3322/canjclin.41.1.19. PMID 1984806. 
  14. ^ Ainsleigh HG (1993). "Beneficial effects of sun exposure on cancer mortality". Prev Med. 22 (1): 132–40. doi:10.1006/pmed.1993.1010. PMID 8475009. 
  15. ^ Farmer, KC; MF Naylor (1996). "Sun exposure, sunscreens, and skin cancer prevention: a year-round concern". Ann Pharmacother 30 (6): 662–673. PMID 8792954. 
  16. ^ Oliveria S, Saraiya M, Geller A, Heneghan M, Jorgensen C (2006). "Sun exposure and risk of melanoma". Arch Dis Child 91 (2): 131–8. doi:10.1136/adc.2005.086918. PMC 2082713. PMID 16326797. 
  17. ^ Wang S, Setlow R, Berwick M, Polsky D, Marghoob A, Kopf A, Bart R (2001). "Ultraviolet A and melanoma: a review". J Am Acad Dermatol 44 (5): 837–46. doi:10.1067/mjd.2001.114594. PMID 11312434. 
  18. ^ The World Health Organization recommends that no person under 18 should use a sunbed
  19. ^ Autier P, Boniol M, Doré JF (July 2007). "Sunscreen use and increased duration of intentional sun exposure: still a burning issue". Int. J. Cancer 121 (1): 1–5. doi:10.1002/ijc.22745. PMID 17415716. 
  20. ^ Gorham ED, Mohr SB, Garland CF, Chaplin G, Garland FC (December 2007). "Do sunscreens increase risk of melanoma in populations residing at higher latitudes?". Ann Epidemiol 17 (12): 956–63. doi:10.1016/j.annepidem.2007.06.008. PMID 18022535. 
  21. ^ Diffey BL (August 2005). "Sunscreens and melanoma: the future looks bright". Br. J. Dermatol. 153 (2): 378–81. doi:10.1111/j.1365-2133.2005.06729.x. PMID 16086753. 
  22. ^ Meredith, Paul; Riesz, Jennifer (2004). "Radiative Relaxation Quantum Yields for Synthetic Eumelanin". Photochemistry and photobiology 79 (2): 211–6. doi:10.1562/0031-8655(2004)079<0211:RCRQYF>2.0.CO;2. PMID 15068035. 
  23. ^ a b Hayden, C G J; Roberts, M S; Benson, H A E (1997). "Systemic absorption of sunscreen after topical application". The Lancet 350 (9081): 863–4. doi:10.1016/S0140-6736(05)62032-6. PMID 9310609. 
  24. ^ Walters, K. A.; Roberts, M. S. (2002). "Percutaneous absorption of sunscreens". Book: Bronaugh, R. L.; Maibach, H.I. Eds. Topical absorption of dermatological products. / New York: Dekker; 2002: 465–81. 
  25. ^ a b Treffel P, Gabard B (May 1996). "Skin penetration and sun protection factor of ultra-violet filters from two vehicles". Pharm. Res. 13 (5): 770–4. doi:10.1023/A:1016012019483. PMID 8860435. 
  26. ^ a b c d Hanson KM, Gratton E, Bardeen CJ (October 2006). "Sunscreen enhancement of UV-induced reactive oxygen species in the skin". Free Radic. Biol. Med. 41 (8): 1205–12. doi:10.1016/j.freeradbiomed.2006.06.011. PMID 17015167. 
  27. ^ a b Mosley CN, Wang L, Gilley S, Wang S, Yu H (June 2007). "Light-induced cytotoxicity and genotoxicity of a sunscreen agent, 2-phenylbenzimidazole in Salmonella typhimurium TA 102 and HaCaT keratinocytes". Int J Environ Res Public Health 4 (2): 126–31. doi:10.3390/ijerph2007040006. PMID 17617675. 
  28. ^ Churg A, Gilks B, Dai J (November 1999). "Induction of fibrogenic mediators by fine and ultrafine titanium dioxide in rat tracheal explants". Am. J. Physiol. 277 (5 Pt 1): L975–82. PMID 10564183. 
  29. ^ [1]
  30. ^ National Toxicology Program. (2012). NTP technical report on the photocarcinogenesis study of retinoic acid and retinyl palmitate [CAS Nos. 302-79-4 (All-trans-retinoic acid) and 79-81-2 (All-trans-retinyl palmitate)] in SKH-1 mice (Simulated solar light and topical application study). Available at http://ntp.niehs.nih.gov/ntp/htdocs/LT_rpts/TR568_508.pdf. Accessed September 19, 2013.
  31. ^ Xu, C.; Green, Adele; Parisi, Alfio; Parsons, Peter G (2001). "Photosensitization of the Sunscreen Octyl p-Dimethylaminobenzoate b UVA in Human Melanocytes but not in Keratinocytes". Photochemistry and Photobiology 73 (6): 600–604. doi:10.1562/0031-8655(2001)073<0600:POTSOP>2.0.CO;2. PMID 11421064. 
  32. ^ Knowland, John; McKenzie, Edward A.; McHugh, Peter J.; Cridland, Nigel A. (1993). "Sunlight-induced mutagenicity of a common sunscreen ingredient". FEBS Letters 324 (3): 309–313. doi:10.1016/0014-5793(93)80141-G. PMID 8405372. 
  33. ^ Damiani E, Greci L, Parsons R, Knowland J (April 1999). "Nitroxide radicals protect DNA from damage when illuminated in vitro in the presence of dibenzoylmethane and a common sunscreen ingredient". Free Radic. Biol. Med. 26 (7–8): 809–16. doi:10.1016/S0891-5849(98)00292-5. PMID 10232823. 
  34. ^ Long SD, Little JB (July 1984). "Sunscreen agents induce DNA repair activity in mouse embryo fibroblasts". J. Environ. Pathol. Toxicol. Oncol. 5 (4–5): 193–200. PMID 6520725. 
  35. ^ Taylor CR, Stern RS, Leyden JJ, Gilchrest BA (January 1990). "Photoaging/photodamage and photoprotection". J. Am. Acad. Dermatol. 22 (1): 1–15. doi:10.1016/0190-9622(90)70001-X. PMID 2405022. 
  36. ^ a b Stevenson, C.; Davies, R. J. H. (1999). "Photosensitization of guanine-specific DNA damage by 2-phenylbenzimidazole and the sunscreen agent 2-phenylbenzimidazole-5-sulfonic acid". Chem. Res. Toxicol. 12 (1): 38–45. doi:10.1021/tx980158l. PMID 9894016. 
  37. ^ Inbaraj, J. J.; Bilski, P.; Chignell, C. F. (2002). "Photophysical and photochemical studies of 2-phenylbenzimidazole and UVB sunscreen 2-phenylbenzimidazole-5-sulfonic acid". Photochem. Photobiol. 75 (2): 107–116. doi:10.1562/0031-8655(2002)075<0107:PAPSOP>2.0.CO;2. PMID 11883597. 
  38. ^ Elisabetta Damiani, Werner Baschong, Lucedio Greci (2007). "UV-Filter combinations under UV-A exposure: Concomitant quantification of over-all spectral stability and molecular integrity". Journal of Photochemistry and Photobiology B: Biology 87 (2): 95–104. doi:10.1016/j.jphotobiol.2007.03.003. PMID 17428672. 
  39. ^ a b Damiani E. Carloni P. Biondi C. Greci L. (2000). "Increased oxidative modification of albumin when illuminated in vitro in the presence of a common sunscreen ingredient: protection by nitroxide radicals – fractionated studies". Free Radical Biology and Medicine 28 (2): 193–201. doi:10.1016/S0891-5849(99)00221-X. PMID 11281286. 
  40. ^ J.M. Allen, C.J. Gosset, A.K. Allen (1996). "Photochemical formation of singlet molecular oxygen in illuminated aqueous solutions of several commercially available sunscreen ingredients". Chem. Res. Toxicol. 9 (3): 605–609. doi:10.1021/tx950197m. PMID 8728505. 
  41. ^ "Nanoparticles Used in Common Household Items Cause Genetic Damage in Mice". 17 November 2009. Retrieved 17 November 2009. 
  42. ^ McCutcheon, J 2014, Is Sunscreen Safe? |url=http://eluxemagazine.com/magazine/is-sunscreen-safe/#sthash.zkXfso6J.dpuf/
  43. ^ Athanasia Varvaresou (2006). "Percutaneous absorption of organic sunscreens". Journal of Cosmetic Dermatology 5 (1): 53–57. doi:10.1111/j.1473-2165.2006.00223.x. PMID 17173572. 
  44. ^ Sheree E Cross; Ruoying Jiang; Heather A E Benson; Michael S Roberts (2001). "Can Increasing the Viscosity of Formulations be used to Reduce the Human Skin Penetration of the Sunscreen Oxybenzone?". Journal of Investigative Dermatology 117 (1): 147–150. doi:10.1046/j.1523-1747.2001.01398.x. PMID 11442762. 
  45. ^ E.Chatelain; B.Gabarda; C.Surber (2003). "Skin Penetration and Sun Protection Factor of Five UV Filters: Effect of the Vehicle" (PDF). Skin Pharmacol Appl Skin Physiol 16 (1): 28–35. doi:10.1159/000068291. PMID 12566826. 
  46. ^ Kerry Hanson skin penetration
  47. ^ R Jiang; M S Roberts; D M Collins; H A E Benson (October 1999). "Absorption of sunscreens across human skin: an evaluation of commercial products for children and adults". Br J Clin Pharmacol. 48 (4): 635–7. doi:10.1046/j.1365-2125.1999.00056.x. PMC 2014387. PMID 10583038. 
  48. ^ http://www.fda.gov/ohrms/dockets/dailys/00/Sep00/090600/c000573_10_Attachment_F.pdf
  49. ^ N. J. Lowe, Physician's guide to sunscreen, Kap. 8, 1991.
  50. ^ Wolf P, Donawho CK, Kripke ML (January 1994). "Effect of sunscreens on UV radiation-induced enhancement of melanoma growth in mice". J. Natl. Cancer Inst. 86 (2): 99–105. doi:10.1093/jnci/86.2.99. PMID 8271307. 
  51. ^ Wulf HC, Poulsen T, Brodthagen H, Hou-Jensen K (August 1982). "Sunscreens for delay of ultraviolet induction of skin tumors". J. Am. Acad. Dermatol. 7 (2): 194–202. doi:10.1016/S0190-9622(82)70108-2. PMID 6982289. 
  52. ^ Reeve VE; Greenoak GE; Gallagher CH; Canfield PJ; Wilkinson FJ (December 1985). "Effect of immunosuppressive agents and sunscreens on UV carcinogenesis in the hairless mouse". Aust J Exp Biol Med Sci 63 (6): 655–65. doi:10.1038/icb.1985.69. PMID 3879583. 
  53. ^ Flindt-Hansen, HP; Thune P, Larsen, TE (1990). "The inhibiting effect of PABA on photocarcinogenesis". Arch Dermatol Res 282 (1): 38–41. doi:10.1007/BF00505643. PMID 2317082. 
  54. ^ Ulrich, C; Degen, A; Patel, MJ; Stockfleth, E (2008). "Sunscreens in organ transplant patients". Nephrol Dial Transplant 23 (6): 1805–1808. doi:10.1093/ndt/gfn292. PMID 18492979. 
  55. ^ Ulrich, C; Hackethal, M; Ulrich, M; Forschner, T; Sterry, W; Stockfleth, E (2008). Prevention of UV-induced infectious and malignant skin diseases in organ transplant patients by regular use of a liposomal sun screen. Berlin. 
  56. ^ Green AC, Williams GM, Logan V, Strutton GM (January 2011). "Reduced melanoma after regular sunscreen use: randomized trial follow-up". J. Clin. Oncol. 29 (3): 257–63. doi:10.1200/JCO.2010.28.7078. PMID 21135266. 

    "For the First Time, Sunscreen Shown to Reduce Melanoma", Nick Mulcahy, Medscape Medical News, January 25, 2011

  57. ^ Gimotty PA, Glanz K (January 2011). "Sunscreen and melanoma: what is the evidence?". J. Clin. Oncol. 29 (3): 249–50. doi:10.1200/JCO.2010.31.7529. PMID 21135278. 
  58. ^ Goldenhersh MA, Koslowsky M (June 2011). "Increased melanoma after regular sunscreen use?". J. Clin. Oncol. 29 (18): e557–8; author reply e859. doi:10.1200/JCO.2011.35.5727. PMID 21537031. 
  59. ^ Lawsuit Filed Against Sunscreen Makers
  60. ^ Sunscreen Scare or Media Hype?, 29 June 2010
  61. ^ FDA proposed changes)(page 49079).
  62. ^ Lautenschlager, Stephan; Wulf, Hans Christian; Pittelkow, Mark R. (2007). "photoprotection". Lancet 370 (9586): 528–37. doi:10.1016/S0140-6736(07)60638-2. PMID 17693182. 
  63. ^ Holick MF (December 2004). "Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease". Am. J. Clin. Nutr. 80 (6 Suppl): 1678S–88S. PMID 15585788. 
  64. ^ Sayre, Robert M.; John C. Dowdy (2007). "Darkness at Noon: Sunscreens and Vitamin D3". Photochemistry and Photobiology 83 (2): 459–63. doi:10.1562/2006-06-29-RC-956. PMID 17115796. 
  65. ^ Nowson C, Margerison C (2002). "Vitamin D intake and vitamin D status of Australians". Med J Aust 177 (3): 149–52. PMID 12149085. 
  66. ^ Grant WB (2002). "An estimate of premature cancer mortality in the U.S. due to inadequate doses of solar ultraviolet-B radiation". Cancer 94 (6): 1867–75. doi:10.1002/cncr.10427. PMID 11920550.