More evidence that sunlight prevents breast cancer and other cancers—at all ages.

Those who would frighten us away from the sun continue to propagandize that sunlight causes cancer. They sometimes have the decency to say “melanoma” rather than lump all cancers together, but they are dead wrong on that front also; most major cancers, including melanoma, are dramatically reduced by regular sunlight exposure (for references, see the cancer section in my book). There have been so many papers written on the protective effects of sunlight and vitamin D on cancer, that most of the newer papers serve primarily as reinforcement for what is already known. A recent study from Ontario, Canada is a case in point.[1] The researchers determined the amount of time spent outdoors by 3,101 women with breast cancer and compared them with 3,471 women who were cancer-free. The ages of the women was also compared to the risk of cancer to determine the differences in breast-cancer risk during different periods of life. High sunlight exposure was considered to be greater than 21 hours outdoors per week; low exposure was considered to be six hours per week or less.

Among teenagers, high sunlight exposure correlated to reduced risk of breast cancer of 29% compared to those who had the lowest exposure; among those in their 20s and 30s, high sunlight exposure correlated to a reduced risk of 36%; among those in their 40s and 50s, a 26% reduced risk; and among those in their 60s and 70s, a 50% reduced risk.

Other researchers have made similar observations. One group demonstrated that girls who had the greatest exposure to sunlight during the ages of 10-19 had a 35% decreased risk of breast cancer as adults when compared to those who had the least exposure.[2]

And what about prostate cancer? It has been established that men who are in the lowest forth of sunlight exposure have three times the risk of developing prostate cancer compared to those in the highest forth.[3] And young boys who are exposed to lots of sunshine have only about one-fifth the risk of contracting prostate cancer—as adults—when compared to those who have had little sun exposure.[4]

So, are the dermatologists doing us a favor by frightening us away from the sun? You may make your own conclusions. Just remember to avoid burning if you choose to enjoy the health benefits of your solar friend.

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[1] Anderson LN, Cotterchio M, Kirsh VA, Knight JA. Ultraviolet Sunlight Exposure During Adolescence and Adulthood and Breast Cancer Risk: A Population-based Case-Control Study Among Ontario Women. Am J Epidemiol. 2011 Jun 9. [Epub ahead of print]

[2] Knight J. et al. Vitamin D and reduced risk of breast cancer: a population-based case-control study. Cancer Epidemiol Biomarkers Prev 2007;16:422-29.

[3] Moon, S. et al. Ultraviolet radiation: effects on risks of prostate and other internal cancers. Mutat Res 2005; 571:207–219.

[4] Luscombe, C. et al. Exposure to ultraviolet radiation: association with susceptibility and age at presentation with prostate cancer. Lancet 2001;358:641–42.

Could the asthma upsurge be due to sunlight and vitamin D deficiency?

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According to the Centers for Disease Control in May 2011, “about one in 12 people in the United States now has asthma—a total of 24.6 million people and an increase of 4.3 million since 2001.”[1]

Researchers in Boston have hypothesized that the decrease in sunlight exposure and resultant vitamin D deficiency is responsible for the asthma epidemic.[2] Others show the same facts: the increase in asthma has paralleled the decline in sunlight exposure, and asthma risk is 40% lower in children of women who have the highest vitamin D consumption during pregnancy.[3] Is it time to return to the sun?

Another study shows an asthma reduction of 52-67%.[4] In that study, THREE-YEAR- OLD CHILDREN WHOSE MOTHERS WERE IN THE HIGHEST QUARTILE OF VITAMIN D CONSUMPTION DURING PREGNANCY HAVE A 61% REDUCED RISK OF A “RECURRENT WHEEZE,” A SYMPTOM OF ASTHMA, WHEN COMPARED TO THOSE WHOSE MOTHERS WERE IN THE LOWEST QUARTILE. The researchers believed that inadequate D levels in the fetus leads to improper development of the lungs and immune system, and they demonstrated that each 100-IU increase in vitamin D consumption resulted in a 19% risk reduction.

A scientific experiment from Australia also demonstrated that when asthmatic mice were exposed to ultraviolet light, before being exposed to an asthma-causing allergen, asthma symptoms were reduced.[5] Considering the yearly $700-million expenditure for Australian asthma-treatment, regular sunlight exposure seems a small price to pay. Tanning beds, like the sun, put forth ultraviolet light to produce vitamin D. These researchers were really using tanning beds for mice! Finally, another recent study from Spain has shown that children exposed to the most sunlight have lower risks of asthma.[6]

Steroids are used as an asthma therapy, but in some individuals, asthma is resistant to steroids. However, when vitamin D3 is added to the steroid treatment, symptoms are greatly reduced.[7] Perhaps sufficient supplementation or sunlight exposure could eliminate steroid need completely. This is the bottom line: children and adults are meant to play outdoors or otherwise be exposed to non-burning ultraviolet B (UVB) light—the most natural way to produce vitamin D. Every child should have a natural life playing outdoors, and both children and adults should regularly have sunlight exposure. It is critical for human health. What a travesty to deprive our children of healthy, normal lives because the Powers of Darkness need to make money selling sunscreens. Be careful not to burn, and enjoy the sun!

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[1]Vital Signs: Asthma Prevalence, Disease Characteristics, and Self-Management Education --- United States, 2001--2009 MMWR, 2011; 60(17);547-552

[2]Litonjua, A. et al. Is vitamin D deficiency to blame for the asthma epidemic? J Allergy Clin Immunol 2007;120:1031-35

[3] Camargo, C. et al. Maternal intake of vitamin D during pregnancy and risk of recurrent wheeze in children at 3 y. Am J Clin Nutr 2007;85:788-95.

[4] Devereux, G. et al. Maternal vitamin D intake and early childhood wheezing. Am J Clin Nutr 2007;85:853-59

[5]Hart, P. et al. Sunlight may protect against asthma. Perth (Australia) Telethon institute for child health research. Quoted in Australian AP Oct 24, 2006.

[6] Arnedo-Pena, A et al. Sunny hours and variations in the prevalence of asthma in schoolchildren according to the International Study of Asthma and Allergies (ISAAC) Phase III in Spain. Int J Biometeorol 2011;55:423-434.

[7]Xystrakis, E. et al. Treatment of Steroid-Resistant Asthma. J Clin Invest 2006;116:146-55

Can sunlight influence fertility and sexual behavior?

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Now that I have your undivided attention, let’s look at the evidence.

Sperm quality and number is superior in men with high vitamin D levels compared with men who are deficient,[i] and other research shows that FEMALE RATS MATED TO DEFICIENT MALES HAVE 73% FEWER SUCCESSFUL PREGNANCIES THAN THOSE MATED TO VITAMIN D-SUFFICIENT MALES.[ii] The ovaries and testes of rats that lack vitamin D receptors (VDR) do not function properly,[iii] and vitamin D deficiency profoundly reduces sperm production;[iv] but that condition is reversible when vitamin D is optimized,[v]--an important fact—since human sperm also contains VDR.[vi]

Dr. Anne Clark assessed the vitamin D levels of about 800 men who were unable to produce a pregnancy in their wives.[vii] About a third had low D levels. After lifestyle changes and vitamin D supplementation, 40% of the men were able to impregnate their wives.

If vitamin D increases fertility, we would expect conception rates to be higher in summer than in winter—and, so it is. Conception rates are highest in late summer.⁵⁴ For those who are having difficulty producing a pregnancy, conception may be as simple as a sunny vacation.

And what about sexuality? There is a direct correlation between high D levels and high testosterone levels in men.[viii] Since testosterone is the “love hormone” in both sexes, libido might be increased by sunlight exposure. Also, D supplementation in testosterone-deficient men increases testosterone by 25% in one year.[ix]

This has been known for decades; in 1939, Dr. Myerson measured circulating testosterone in men and exposed their various body parts to UV.[x] AFTER FIVE DAYS OF CHEST EXPOSURE, TESTOSTERONE INCREASED 120%. WHEN GENITALS WERE EXPOSED, TESTOSTERONE INCREASED BY 200%! Considering the current cultural obsession with sex, I’m surprised that no one has followed up on Myerson’s work. The light emitted from tanning beds is the same type of light used by Dr. Myerson. I expect that many people may have a totally new concept of the much-maligned tanning bed if this information is widely promulgated.

[i] Bjerrum, Poul et al. Vitamin D is positively associated with sperm motility and increases intracellular calcium in human spermatozoa. Human Reproduction 2011;26:1307-1317.

[ii] Kwiecinski, G. et al. Vitamin D is necessary for reproductive functions of the male rat. J Nutr 1989;119:741-44.

[iii] Kinuta, K. et al. Vitamin D is an important factor in estrogen biosynthesis in both female and male gonads. Endocrinology 2000;141:1317.

[iv] Sood, S. et al. Effect of vitamin D deficiency on testicular function in the rat. Ann Nutr Metab 1992;36:203-8.

[v] Sood, S. et al. Effect of vitamin D repletion on testicular function in vitamin-D deficient rats. Ann Nutr Metab 1995;95-98

vi] Corbett, S. et al. Vitamin d receptor found in human sperm. Urology 2006;68:1345-49

[vii] Clark, Anne. Fertility Society of Australia conference in Brisbane - paper presented by D. Clark - research was part of a doctoral study by University of Sydney student Laura Thomson. News.com.au Oct 19 2008

[viii] Wehr, E et al. Association of vitamin D status with serum androgen levels in men. Clin Endocrinol (Oxf) 2010;73(2):243-8

[ix] Pilz, S. et al. Effect of vitamin D supplementation on testosterone levels in men. Horm Metab Res 2011;43(3):223-5

[x] Myerson, A. Influence of ultraviolet radiation on excretion of sex hormones in the male. Endocrinology 1939;25:7-12

Vitamin D, Sunlight and Pneumonia

A new analysis of vitamin D levels among winter pneumonia patients has produced some very interesting observations:

1. Those admitted to the Waikato, New Zealand hospital with severe vitamin D deficiency were more likely to die within a month compared to those who had normal or only slightly low levels.

2. The overall death rate was 29% for those with severe D deficiency, and only 4% for those with higher levels. This could indicate that vitamin D deficiency causes a 700% increase in the risk of death by pneumonia. Follow this link to read more about the research: http://news.xinhuanet.com/english2010/health/2011-05/13/c_13873372.htm

The authors noted that sunlight is the best source of vitamin D, and that winters in Hamilton, New Zealand area, like most temperate areas of the world, do not allow sufficient sunlight to stimulate vitamin D production. They also state that pneumonia is the single largest cause of death in children worldwide, killing about 1.6 million children under the age of five each year.

What a horror that so many countries, by means of their health departments and dermatological societies, are frightening children and their parents away from the sunlight during the seasons of the year when it is available. This ensures that vitamin D deficiency will ensue in winter. Also, at the very least, supplementation of vitamin D3 should be recommended during winter—supplementation of about 1,000 IU for every 25 pounds of bodyweight.

This is not the first time the relationship between pneumonia and sunlight has been observed. In 2003, Dr. Dowell and his colleagues showed that the disease is seasonal, with the lowest rates in summer, an increase in fall and a peak in winter.[1] This relationship exactly mimics the quantity of sunlight exposure available in different seasons. Other research has pointed out the same relationship,[2] [3]and still other studies have shown the importance of vitamin D in prevention of pneumonia and related infections to it,[4]

A popular fitness guru used to scream the slogan, “Stop the insanity!” I agree with her advice as it relates to sunlight exposure and would like to scream that it is insane for medical and governmental organizations to frighten their citizens out of the sunlight. Sunshine has become one of our most critical health needs, and those who would have us avoid it at all costs have blood on their hands.

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[1] Dowell, S. et al. Seasonal patterns of invasive pneumococcal disease. Emerg Infect Dis 2003;9:573-9.

[2] Leow L, Simpson T, Cursons R, Karalus N, Hancox RJ. Vitamin D, innate immunity and outcomes in community acquired pneumonia. Respirology. 2011;16(4):611-6

[3] White AN, Ng V, Spain CV, Johnson CC, Kinlin LM, Fisman DN. Let the sun shine in: effects of ultraviolet radiation on invasive pneumococcal disease risk in Philadelphia, Pennsylvania. BMC Infect Dis. 2009 Dec 4;9:196.

[4] Oduwole AO, Renner JK, Disu E, Ibitoye E, Emokpae E. Relationship between Vitamin D Levels and Outcome of Pneumonia in Children. West Afr J Med 2010;29(6):373-8.

Tanning beds, sunlight, vitamin D and superb bone strength. Can tanning beds produce the World’s strongest bones?

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Can tanning beds or sunlight produce sufficient vitamin D to produce superbly strong bones? The answer appears to be “yes.”

I am part of an email list of persons who are intensely interested in vitamin D research and who share articles on vitamin D and sunlight as preventive therapies for various diseases. I recently received a most interesting email from Rufus Greenbaum, who lives in the UK and who organizes vitamin D symposiums there. He had met a man who had been using a tanning bed twice weekly since 1970 and who had just completed a bone densitometer test, known as a DEXA scan. On viewing the results of the scan, his doctor told him “You have the strongest bones that I have ever seen.”

That news certainly came as no shock. Conventional tanning beds produce vast quantities of vitamin D in short periods of time,[1] and vitamin D is absolutely essential for optimal absorption of calcium in the gut.[2] [3] Without calcium absorption, vast quantities of ingested calcium will make little difference to bone strength; much of the calcium will be passed through the intestine and flushed down the toilet. It is already known that people who use tanning beds have dramatically stronger bones and higher blood-vitamin D levels than those who don’t use them.[4]

Both tanning beds and sunlight enhance the levels of vitamin D in the skin by producing UVB light, which converts cholesterol in the skin to vitamin D. In fact, ninety percent of the vitamin D produced in the US population is due to sunlight exposure.[5]

Research has shown that daily sunlight exposure in elderly women, during a period of one year, increased serum vitamin D levels by 400% and decreased the risk of hip fractures dramatically.[6] A control group, who did not receive sunlight exposure, had six fractures for each fracture experienced by the sunlight-exposed group. The message is that sunlight exposure may decrease the risk of osteoporotic fractures by 84%! Finally, and even more impressively, research from Spain showed that among women who actively sought the sunlight, the risk of fractures was only one-eleventh that of women who spent most of their lives indoors.[7] This begs the questions: Should we really avoid sunlight and tanning beds like the plague? Is such avoidance worth the risk of dying from osteoporotic fractures?

The key to safe exposure to sunlight or sunlamps is to be sure not to burn. And for those who are frightened about melanoma, please read my previous blogs on the subjects: http://drsorenson.blogspot.com/2010/07/exposing-melanoma-fraud-part-1.html

http://drsorenson.blogspot.com/2010/07/exposing-sunlightmelanoma-fraud-part-2.html

http://drsorenson.blogspot.com/2011/03/sunshine-weekends-and-vitamin-d-may.html

http://drsorenson.blogspot.com/2009/12/melanoma-midsummer-nights-dream-or.html

[1] Grant, W. Personal communication with the author, June, 2006

[2] Heaney, R. et al. Calcium Absorption Varies within the Reference Range for Serum 25-Hydroxyvitamin D. Journal of the American College of Nutrition 2003; 22: 142–146.

[3] Heaney, R. Vitamin D and calcium interactions: functional outcomes. Am J Clin Nutr 2008;88(suppl):541S–4S

[4 Tangpricha V. et al. Tanning is associated with optimal vitamin D status (serum 25-hydroxyvitamin D concentration) and higher bone mineral density. Am J Clin Nutr 2004;80:1645-49.

[5] Reichrath J. The challenge resulting from positive and negative effects of sunlight: how much solar UV exposure is appropriate to balance between risks of vitamin D deficiency and skin cancer? Prog Biophys Mol Biol 2006;92(1):9-16

[6 Sato Y, Metoki N, Iwamoto J, Satoh K. Amelioration of osteoporosis and hypovitaminosis D by sunlight exposure in stroke patients. Neurology 2003;61(3):338-42.

[7] Larrosa, M. Vitamin D deficiency and related factors in patients with osteoporotic hip fracture. Med Clin (BARC) 2008;130:6-9.

Can Sunlight and Vitamin D reduce the risk of Crohn’s Disease?

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Crohn’s Disease is a nasty autoimmune bowel disease that causes abdominal pain, inflammation and fibrous tissue buildup. It is increasing in incidence, particularly among people younger than 20,[1] a group that spends less time outdoors each passing year. Unfortunately and unnaturally, young people spend their time in indoor activities, and when venturing outdoors are advised by their parents and medical “experts” to dutifully apply sunscreen, which can reduce the production of vitamin D in the skin by up to 99%.[2]

Crohn’s is closely correlated to vitamin D deficiency, and moderate sunlight exposure coupled with winter supplementation has been recommended in the past to reduce its severity. Fifty percent of Crohn’s patients have levels of vitamin D below 20 ng/ml (very deficient) in winter and 19% in summer.[3]

Suffice it to say (without reviewing the copious research indicating that sunlight and vitamin D correlate to lower risk of many autoimmune diseases), it appears that sunlight exposure may help to reduce the risk of Crohn’s. The latest indication is a study from France, demonstrating that people living in geographic areas of lowest sunlight exposure have a substantially higher risk of Crohn’s disease.[4] This disease is just one of more than 100 that correlate closely to deficiency of sunlight and vitamin D, yet we continue to see warnings by dermatologists to avoid the sun. When will they ever learn?

Non-burning sunlight exposure is a boon to mankind, and it does not cause melanoma. Read my book for more information or see my earlier blogs on the subject of melanoma and sunlight.

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[1] Chouraki V, et al "The changing pattern of Crohn's disease incidence according to age in northern France: a constant increase in the 0-19 years age group (1988-2005)" DDW 2009; Abstract 114.

[2] Matsuoka, L. et al. sunscreens suppress cutaneous vitamin D3 synthesis. Journal of Clinical Endocrinology & Metabolism 1987; 64:1165-68

[3] Gilman, J. et al. Determinants of vitamin D status in adult Crohn’s disease patients, with particular emphasis on supplemental vitamin D use. Eur J Clin Nutr. 2006;60(7):889-96

[4] Nerich, V. et al. Low exposure to sunlight is a risk factor for Crohn's disease. Aliment Pharmacol Ther 2011;33(8):940-945.

Sunshine weekends and vitamin D may save you from melanoma

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Sunlight, and plenty of it, may be the best method for reducing the risk of melanoma. An impressive piece of research on melanoma and sunlight appeared recently in the European Journal of Cancer.[1] Dr. Julia Newton Bishop and colleagues (thirteen scientists in all) researched sunlight exposure habits and compared those habits to the risk of melanoma in an English population. Among other notable findings was a considerable reduction in melanoma risk among those who received the highest summer sunlight exposure on weekends. Compared to those with the least exposure to sunlight on weekends, those who received 4-5 hours of sunlight during the weekends had a reduced risk of melanoma of 28%, and those who received more than 5 hours had a reduced risk of melanoma of 33%.

In general, the English have very light complexions—complexions that are known to be more susceptible to melanoma, a fact that makes the research even more interesting. One can only conclude from this information that regular sunlight exposure protects against melanoma. In reality, this result should come as no surprise; at least 16 studies have shown indoor workers are much more likely to contract melanoma than outdoor workers.[2] Other research points out that melanomas occur much more frequently on areas of the body that receive little or no exposure to sunlight.[3]

Finally, it is quite obvious that outdoor living has decreased dramatically since 1935. Based on materials furnished by the Department of Labor Statistics, I calculated that sunlight exposure has decreased by at least 83%..[4] Yet, the Melanoma International Foundation has stated, “Melanoma is epidemic: rising faster than any other cancer and projected to affect one person in 50 by 2010, currently it affects 1 in 75 . In 1935, only one in 1500 was struck by the disease.” In other words, as sunlight exposure has dropped profoundly, melanoma risk has increased by 3,000%! Based on those facts, the idea—that sunlight exposure is the cause of melanoma—is counterintuitive at best, and ludicrous at worst.

It is likely that vitamin D production in the skin, in response to sunlight, is a major player in reducing the risk of melanoma. Enzymes in melanoma cells form active vitamin D[5], which in turn can lead to melanoma cell death,[6] and in lab experiments, active vitamin D can destroy melanoma cells.[7] In fact, vitamin D works in many ways to reduce cancer. Here are just a few:

1. Vitamin D promotes apoptosis (normal cell death) so that cancer cells die normally.[8]

2. Vitamin D inhibits proliferation (out-of-control growth) of cancer cells.[9]

3. Vitamin D inhibits angiogenesis in cancerous tissue. Angiogenesis is the formation of blood vessels. It is a process that provides blood and nutrients to newly formed tissue. If angiogenesis in cancer cells can be stopped, the cells die. Vitamin D acts a selective angiogenesis inhibitor—it retards the growth of new, undesirable “feeder” blood vessels into cancer cells.[10]

4. Vitamin D inhibits metastasis (the spreading of cancer cells from the initial location of the disease to another location).[11]

The key to safe sunlight exposure is to avoid burning and to gradually develop a tan. Caution is always in order. To prevent melanoma, we need not to avoid the sunlight but safely embrace it!

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[1] Newton-Bishop, J et. al. Relationship between sun exposure and melanoma risk for tumours in different body sites in a large case-control study in a temperate climate. European Journal of Cancer 2011; 4 7; 7 3 2 –7 4 1.

[2] Lee J. Melanoma and exposure to sunlight. Epidemiol Rev 1982;4:110–36.

Vågero D, Ringbäck G, Kiviranta H. Melanoma and other tumors of the skin among office, other indoor and outdoor workers in Sweden 1961–1979 Brit J Cancer 1986;53:507–12.

Kennedy C, Bajdik CD, Willemze R, De Gruijl FR, Bouwes Bavinck JN; Leiden Skin Cancer Study. The influence of painful sunburns and lifetime sun exposure on the risk of actinic keratoses, seborrheic warts, melanocytic nevi, atypical nevi, and skin cancer. Invest Dermatol 2003;120:1087–93.

Garland FC, White MR, Garland CF, Shaw E, Gorham ED. Occupational sunlight exposure and melanoma in the USA Navy. Arch Environ Health 1990; 45:261-67.

Kaskel P, Sander S, Kron M, Kind P, Peter RU, Krähn G. Outdoor activities in childhood: a protective factor for cutaneous melanoma? Results of a case-control study in 271 matched pairs. Br J Dermatol 2001;145:602-09.

Garsaud P, Boisseau-Garsaud AM, Ossondo M, Azaloux H, Escanmant P, Le Mab G. Epidemiology of cutaneous melanoma in the French West Indies (Martinique). Am J Epidemiol 1998;147:66-8.

Le Marchand l, Saltzman S, Hankin JH, Wilkens LR, Franke SJM, Kolonel N. Sun exposure, diet and melanoma in Hawaii Caucasians. Am J Epidemiol 2006;164:232-45.

Armstong K, Kricker A. The epidemiology of UV induced skin cancer. J Photochem Biol 2001;63:8-18

Crombie IK. Distribution of malignant melanoma on the body surface. Br J Cancer 1981;43:842-9.

Crombie IK. Variation of melanoma incidence with latitude in North America and Europe. Br J Cancer 1979;40:774-81.

Weinstock MA, Colditz,BA, Willett WC, Stampfer MJ. Bronstein, BR, Speizer FE. Nonfamilial cutaneous melanoma incidence in women associated with sun exposure before 20 years of age. Pediatrics 1989;84:199-204.

Tucker MA, Goldstein AM. Melanoma etiology: where are we? Oncogene 20f03;22:3042-52.

Berwick M, Armstrong BK, Ben-Porat L, Fine J, Kricker A, Eberle C. Sun exposure and mortality from melanoma. J Nat Cancer Inst 2005;97:95-199.

Veierød MB, Weiderpass E, Thörn M, Hansson J, Lund E, Armstrong B. A prospective study of pigmentation, sun exposure, and risk of cutaneous malignant melanoma in women. J Natl Cancer Inst 2003;95:1530-8.

Oliveria SA, Saraiya M, Geller AC, Heneghan MK, Jorgensen C. Sun exposure and risk of melanoma. Arch Dis Child 2006;91:131-8.

Elwood JM, Gallagher RP, Hill GB, Pearson JCG. Cutaneous melanoma in relation to intermittent and constant sun exposure—the western Canada melanoma study. Int J Cancer 2006;35:427-33

[3] Garland FC, White MR, Garland CF, Shaw E, Gorham ED. Occupational sunlight exposure and melanoma in the USA Navy. Arch Environ Health 1990; 45:261-67.

Rivers, J. Is there more than one road to melanoma? Lancet 2004;363:728-30.

Crombie, I. Racial differences in melanoma incidence. Br J Cancer 1979;40:185-93.

[4] Ian D. Wyatt and Daniel E. Hecker. Occupational changes in the 20th century. Monthly Labor Review, March 2006 pp 35-57: Office of Occupational Statistics and Employment Projections, Bureau of Labor Statistics.

[5] Chida K, Hashiba H, Fukushima M, Suda T, Kuroki T. Inhibition of tumor promotion in mouse skin by 1 alpha, 25-dihydroxyvitamin D3. J Cancer Res 1985;45:5426–30.

[6] Evans SR, Houghton AM, Schumaker L, Brenner RV, Buras RR, Davoodi F, et al. Vitamin D receptor and growth inhibition by 1, 25-dihydroxyvitamin D3 in human malignant melanoma cell lines. J Surg Res 1996;61:127–33.

[7] Seifert M, Diesel B, Meese E, Tilgen W, Reichrath J. Expression of 25-hydroxyvitamin D-1alpha-hydroxylase in malignant melanoma: implications for growth control via local synthesis of 1,25(OH)D and detection of multiple

splice variants. Exp Dermatol 2005;14:153–4.

[8] Diaz, G. et al. Apoptosis is induced by the active metabolite of vitamin D3 and its analogue EB1089 in colorectal adenoma and carcinoma cells: possible implications for prevention and therapy. Cancer Res 2000;60:2304-12.

Swamy, N. et al. Inhibition of proliferation and induction of apoptosis by 25-hydroxyvitamin D3-3beta-(2)-Bromoacetate, a nontoxic and vitamin D receptor-alkylating analog of 25-hydroxyvitamin D3 in prostate cancer cells. Clin Cancer Res. 2004;10:8018-27.

Miller, E. et l. Calcium, vitamin D, and apoptosis in the rectal epithelium. Cancer Epidemiology Biomarkers & Prevention 2005;14: 525-28.

[9] Swamy, N. et al. Inhibition of proliferation and induction of apoptosis by 25-hydroxyvitamin D3-3beta-(2)-Bromoacetate, a nontoxic and vitamin D receptor-alkylating analog of 25-hydroxyvitamin D3 in prostate cancer cells. Clin Cancer Res. 2004;10:8018-27.

[10] Mantell, D. et al. 1,25-Dihydroxyvitamin D3 inhibits angiogenesis in vitro and in vivo. Circulation Research. 2000;87:214.

[11] Nakagawa K. et al. 1alpha,25-Dihydroxyvitamin D(3) is a preventive factor in the metastasis of lung cancer. Carcinogenesis 2005;26:429-40.

El Abdaimi, K. et al. The vitamin D analogue EB 1089 prevents skeletal metastasis and prolongs survival time in nude mice transplanted with human breast cancer cells. Cancer Research 2000;60:4412-4418.

Lokeshwar B. et al. Inhibition of prostate cancer metastasis in vivo: a comparison of 1,23-dihydroxyvitamin D (calcitriol) and EB1089. Cancer Epidemiol Biomarkers Rev. 1999;8:241-48.