By William B. Grant, Ph.D.
SUNARC

With all of the publicity that UV radiation (UVR) is an important cause of skin cancer, premature skin aging and cataract formation, one might think that avoidance of UVR would be the best policy. Not so fast. If protection against UVR were the most important thing, all humans would have very dark skin, since the melanin in dark skin protects against skin cancer and premature skin aging.

Skin pigmentation becomes paler the closer one’s ancestors lived to the polar-regions, evidently to balance cutaneous production of vitamin D with protection against free radicals and DNA damage from UVR [Jablonski and Chaplin, 2000]. In addition, even a cursory look at the geographic variation in cancer mortality rates in the United States [Devesa et al., 1999] indicates that some environmental factor has to explain why mortality rates for a number of internal cancers are approximately twice as high in northeastern, highly-urbanized states than in southwestern, more rural states.

Diet and smoking are, of course, important risk factors for many types of cancer [Doll and Peto, 1981]. But in order for diet to explain the geographic variation in cancer rates, Americans would need to be eating drastically different diets by region. However, anyone who has travelled throughout the United States knows that the food choices do not vary much anywhere in the contiguous 48 states.

The Risk of Cancer Lessens With More Sun Exposure

The key to understanding this geographic pattern was provided by Cedric and Frank Garland in 1980 [Garland and Garland, 1980]. They reasoned that sunlight, through the production of vitamin D, reduced the risk of colon cancer in the sunny areas compared to that in the darker areas. They performed an ecologic study of annual solar irradiance versus colon cancer mortality rates and found a strong inverse correlation, i.e. the more sunlight, the less cancer. (An ecologic study treats entire populations defined geographically as entities, with values for disease outcome and environmental or dietary factors averaged for each entity.)

Their paper received little notice at first, perhaps because UVR was commonly associated with skin cancer, perhaps because the ecologic approach was falling out of favor [Doll and Peto, 1981]. Undaunted, they extended their work through the use of stored serum 25-hydroxyvitamin D (25(OH)D)--the common form of circulating vitamin D--values for another purpose along with a determination of colorectal cancer incidence among the serum donors, finding a significant inverse correlation between 25(OH)D and colorectal cancer rates [Garland et al., 1985]. The list of cancers for which ultraviolet B (UVB) (290-315 nm) and vitamin D is protective was extended through a variety of observational epidemiologic studies by the end of the 1990s to include breast, ovarian and prostate cancer and non-Hodgkin’s lymphoma [Grant, 2002b].

How Vitamin D Reduces the Risk of Cancer

The mechanisms by which vitamin D reduces the risk of cancer are fairly well understood. They include enhancing calcium absorption (in the case of colorectal cancer) [Lamprecht and Lipkin, 2003], inducing cell differentiation, increasing cancer cell apoptosis or death, reducing metastasis and proliferation, and reducing angiogenesis [van den Bemd and Chang, 2002]. In addition, 25(OH)D downregulates parathyroid hormone (PTH) [Chapuy et al., 1987]. Since IGF-I stimulates tumor growth and high quantities are a consequence of the standard American diet [Grant, 2002a; 2004], vitamin D can be considered one partial antidote to the American diet.

When I decided to investigate the role of UVB and vitamin D in reducing the risk of cancer, after I convinced myself that dietary factors could not explain the geographic variation of cancer mortality rates in the United States, I posed two questions to address:

• For how many cancers is UVB/vitamin D protective?
• How many Americans die prematurely each year due to inadequate levels of vitamin D?
  

I started with the maps of cancer mortality rates in the Atlas of Cancer Mortality [Devesa et al., 1999] and found the UVB irradiance/dose map for the United States for July 1992 made using data obtained by NASA’s Total Ozone Mapping Spectrometer (TOMS) to use as a proxy for vitamin D production. In this study, I determined that UVB was inversely correlated with mortality rates for 12 types of cancer, including five types of cancer already identified plus an additional seven, and estimated that 17, 000 to 23,000 Americans died prematurely each year due to insufficient vitamin D [Grant, 2002b].

While the study was generally accepted, critics pointed out that I had ignored a number of factors that affect the risk of cancer and which could, perhaps, explain much of the variation in mortality rates. To respond to these critics, I extended the analysis by including a number of cancer risk factors for which I could find state-averaged values.

These factors included lung cancer mortality rates (an index for the adverse health effects of smoking), fraction of the population considered of Hispanic heritage (Hispanics are counted as white Americans in the Atlas), alcohol consumption rates, degree of urbanization, and fraction of the population living below the poverty level.

Sun Exposure (UVB) Protects Against 16 Types of Cancer

The new study links UVB as protective to a total of 16 types of cancer, primarily epithelial (pertaining to the surface) cancers of the digestive and reproductive systems [Grant, submitted]. Six types of cancer (breast, colon, endometrial, esophageal, ovarian, and non-Hodgkin’s lymphoma) were inversely correlated to solar UVB radiation and rural residence in combination. This result strongly suggests that living in an urban environment is associated with reduced UVB exposure compared to living in a rural environment.

Another 10 types of cancer including bladder, gallbladder, gastric, pancreatic, prostate, rectal and renal were inversely correlated with UVB but not urban residence. Ten types of cancer were significantly correlated with smoking, six types with alcohol, and seven types with Hispanic heritage. Poverty status was inversely correlated with seven types of cancer. Since the results for alcohol, Hispanic heritage, and smoking for white Americans agree well with the literature [Trapido et al., 1995; Thun et al., 2002], they provide a high level of confidence in the approach and its results for UVB radiation.

Over 40,000 Americans Die Annually From Cancer Caused by Vitamin D Deficiency

From this analysis, it was estimated that 45,000 Americans die from cancer annually related to inadequate levels of vitamin D: half from UVB doses based on location, and half based on living in an urban environment with reduced solar radiation exposure.

Papers continue to appear supporting the UVB/vitamin D-cancer connection. The latest is from Norway, showing that the detection of breast, colon, and prostate cancer has a seasonal cycle correlated with vitamin D production by sunlight [Robsahm et al., 2004]. This paper is important since it shows that vitamin D effectively fights cancer even in the later stages.

How Much Vitamin D is Required to Prevent Cancer?

The amount of ingested vitamin D and/or UVB exposure required for optimal protection against cancer is still being determined. Each person responds differently to UVB exposure and oral intake of vitamin D depending on such factors as skin pigmentation, body mass index (vitamin D is fat soluble), age, condition of digestive tract, other dietary factors, etc.

Dietary vitamin D is insufficient alone to significantly reduce the risk of most cancers since the ingested amounts, up to 200 to 400 I.U. per day, are too low [Grant and Garland, in press]. Evidently, 600 to 1000 I.U per day are required to reduce the risk of vitamin-D-sensitive cancers, except possibly prostate cancer, for which population-average values of serum 25(OH)D are associated with the minimum risk [Tuohimaa et al., 2004; Grant, in press].

The current understanding is that serum 25(OH)D levels should be in the 30 to 40 ng/ml (75-100 nmol/L) range for cancer prevention and optimal health. The only way to determine one’s 25(OH)D levels is through blood tests, which can be ordered through a physician or nutritionist. It should be noted that the UVB dose required to generate these levels is much less than would ordinarily be considered a risk factor for skin cancer, etc.

The time required in the sun is probably 15 to 30 minutes per day with at least hands and face exposed in the mid-latitudes during summer [Reid et al., 1986], but depends on a number of personal factors. The optimal time for solar UVB production of vitamin D may be around the middle of the day when the ratio of UVB to UVA (315-400 nm) is highest and the required exposure times are shortest.

However, this works only when the sun is elevated high enough--for the four to five darkest months of the year it is impossible to produce any vitamin D from sunlight in Boston [Webb et al., 1988]. When solar UVB is not available, one has to rely on stored vitamin D (weeks to months), artificial UVB, dietary supplements, many types of fish, or fortified foods, which now include milk and orange juice.

How Can You Protect Yourself From Inadequate Vitamin D Levels?

While the scientific results to date increasingly support the hypothesis that UVB and vitamin D reduce the risk of many types of cancer as well as many other types of disease including musculoskeletal diseases, autoimmune diseases and hypertension, it will likely be some time before the health system embraces this hypothesis and acts to recommend higher values of 25(OH)D, which would require increased UVB exposure (natural and artificial) and dietary supplements.

However, the informed individual who carefully studies the literature can very likely reduce his or her risk of cancer and a number of other diseases by careful exposure to UVB, being particularly careful to avoid any sunburning, and adequate intake of vitamin D.

More information on the protective role of UVB against breast and colorectal cancer, other cancers, and other diseases can be found at my Web site, www.sunarc.org.

William B. Grant has a Ph.D. in physics from U.C. Berkeley and has worked at the level of senior research scientist in the fields of optical and laser remote sensing of the atmosphere and atmospheric sciences at SRI International, the Jet Propulsion Laboratory, and the NASA Langley Research Center. He is the author or coauthor of over 60 articles in peer-reviewed journals, has edited two books of reprints, and contributed half a dozen chapters to other books.

He published the first paper linking diet to Alzheimer's disease and identifying the major dietary components that are risk and risk reduction factors. He has also studied the links between dietary sugars and heart disease and obesity, diet and breast, colon and prostate cancer, and UVB/vitamin D and cancer and autoimmune diseases. He recently retired from NASA and founded Sunlight, Nutrition and Health Research Center (SUNARC), where he will continue and extend his health research and educational efforts.

References:

1. Chapuy MC, Chapuy P, Meunier PJ. Calcium and vitamin D supplements: effects on calcium metabolism in elderly people. Am J Clin Nutr. 1987;46:324-8.

2. Devesa SS, Grauman DJ, Blot WJ, Pennello GA, Hoover RN, Fraumeni JF Jr., Atlas of Cancer Mortality in the United States, 1950-1994. NIH Publication No. 99-4564, 1999. website (accessed March 3, 2004).

3. Doll R, Peto R. The causes of cancer: quantitative estimates of avoidable risks of cancer in the United States today. J Natl Cancer Inst. 1981;66:1191-308.

4. Garland CF, Garland FC. Do sunlight and vitamin D reduce the likelihood of colon cancer? Int J Epidemiol. 1980;9:227-31.

5. Garland C, Shekelle RB, Barrett-Connor E, Criqui MH, Rossof AH, Paul O. Dietary vitamin D and calcium and risk of colorectal cancer: a 19-year prospective study in men. Lancet. 1985;1:307-9.

6. Grant WB. An estimate of premature cancer mortality in the United States due to inadequate doses of solar ultraviolet-B radiation, Cancer, 2002b;94:1867-75.

7. Grant WB. A multicountry ecologic study of risk and risk reduction factors for prostate cancer mortality. Eur Urol. 2004;45:371-9.

8. Grant WB. Geographic variation of prostate cancer mortality rates in the U.S.A.; implications for prostate cancer risk related to vitamin D; Int. J. Cancer, in press.

9. Grant WB, Garland CF. A critical review of studies on vitamin D in relation to colorectal cancer. Nutrition Cancer, in press.

10. Herman JR, Krotkov N, Celarier E, Larko E, Labow G. Distribution of UV radiation at the Earth's surface from TOMS-measured UV-backscattered radiances. J Geophys Res-Atmos. 1999;104:12,059-12,076. website (accessed February 25, 2004).

11. Jablonski NG, Chaplin G. The evolution of human skin coloration. J Hum Evol. 2000;39:57-106.

12. Lamprecht SA, Lipkin M. Chemoprevention of colon cancer by calcium, vitamin D and folate: molecular mechanisms. Nat Rev Cancer. 2003;3:601-14.

13. Reid IR, Gallagher DJ, Bosworth J. Prophylaxis against vitamin D deficiency in the elderly by regular sunlight exposure. Age Ageing. 1986;15:35-40.

14. Robsahm TE, Tretli S, Dahlback A, Moan J. Vitamin D(3) from sunlight may improve the prognosis of breast-, colon- and prostate cancer (Norway). Cancer Causes Control. 2004;15:149-58.

15. Thun MJ, Henley SJ, Calle EE. Tobacco use and cancer: an epidemiologic perspective for geneticists. Oncogene 2002;21:7307-25.

16. Tuohimaa P, Tenkanen L, Ahonen M, et al. Both high and low levels of blood vitamin D are associated with a higher prostate cancer risk: a longitudinal, nested case-control study in the Nordic countries. Int J Cancer. 2004;108:104-8.

17. van den Bemd GJ, Chang GT. Vitamin D and vitamin D analogs in cancer treatment. Curr Drug Targets. 2002;3:85-94.

18. Webb AR, Kline L, Holick MF. Influence of season and latitude on the cutaneous synthesis of vitamin D3: exposure to winter sunlight in Boston and Edmonton will not promote vitamin D3 synthesis in human skin. J Clin Endocrinol Metab. 1988;67:373-8.

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