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The association of solar ultraviolet B (UVB) with reducing risk of cancer: multifactorial ecologic analysis of geographic variation in age-adjusted cancer mortality rates. Grant WB, Garland CF. Anticancer Res. 2006 Jul-Aug;26(4A):2687-99. PMID: 16886679 CONCLUSION: These results provide additional support for the hypothesis that solar UVB, through photosynthesis of vitamin D, is inversely-associated with cancer mortality rates, and that various other cancer risk-modifying factors do not detract from this link. It is thought that sun avoidance practices after 1980, along with improved cancer treatment, led to reduced associations in the latter period. The results regarding solar UVB should be studied further with additional observational and intervention studies of vitamin D indices and cancer incidence, mortality and survival rates.

Comment: Although lower risk associated with vitamin D exposure was shown most consistently for ER+/PR+ tumors, the result might simply reflect that this tumor subtype was the most common. Nonetheless, these findings support vitamin D's beneficial effects on breast cancer risk, regardless of hormone-receptor status. Sun exposure and dietary intake (Table 1) are key sources of vitamin D.

Vitamin D from dietary intake and sunlight exposure and the risk of hormone-receptor-defined breast cancer. Blackmore KM, Lesosky M, Barnett H, Raboud JM, Vieth R, Knight JA. Am J Epidemiol. 2008 Oct 15;168(8):915-24. Epub 2008 Aug 27. PMID: 18756015 doi:10.1093/aje/kwn198 This study suggests that vitamin D is associated with a reduced risk of breast cancer regardless of ER/PR status of the tumor. Future studies with a larger number of receptor-negative and mixed tumors are required.

Use of cod liver oil during the first year of life is associated with lower risk of childhood-onset type 1 diabetes: a large, population-based, case-control study. Stene LC, Joner G; Norwegian Childhood Diabetes Study Group. Am J Clin Nutr. 2003 Dec;78(6):1128-34. PMID: 14668274 Conclusion: Cod liver oil may reduce the risk of type 1 diabetes, perhaps through the antiinflammatory effects of long-chain n-3 fatty acids.

Serum 25-hydroxyvitamin D and colon cancer: eight-year prospective study. Garland CF, Comstock GW, Garland FC, Helsing KJ, Shaw EK, Gorham ED. Lancet. 1989 Nov 18;2(8673):1176-8. PMID: 2572900 Blood samples taken in 1974 in Washington County, Maryland, from 25 620 volunteers were used to investigate the relation of serum 25-hydroxyvitamin D (25-OHD) with subsequent risk of getting colon cancer. 34 cases of colon cancer diagnosed between August, 1975, and January, 1983, were matched to 67 controls by age, race, sex, and month blood was taken. Risk of colon cancer was reduced by 75% in the third quintile (27-32 ng/ml) and by 80% in the fourth quintile (33-41 ng/ml) of serum 25-OHD. Risk of getting colon cancer decreased three-fold in people with a serum 25-OHD concentration of 20 ng/ml or more. The results are consistent with a protective effect of serum 25-OHD on colon cancer.

Review article: vitamin D acquisition and breast cancer risk. Pérez-López FR, Chedraui P, Haya J. Reprod Sci. 2009 Jan;16(1):7-19. Review. PMID: 19144887 DOI: 10.1177/1933719108327595 Conclusions: Although there are controversial results, it seems plausible that sufficient endogenous vitamin D levels may have a protective function on mammary cells, reducing breast cancer risk.

Serum levels of vitamin D metabolites and breast cancer risk in the prostate, lung, colorectal, and ovarian cancer screening trial. Freedman DM, Chang SC, Falk RT, Purdue MP, Huang WY, McCarty CA, Hollis BW, Graubard BI, Berg CD, Ziegler RG. Cancer Epidemiol Biomarkers Prev. 2008 Apr;17(4):889-94. Epub 2008 Apr 1. PMID: 18381472 doi: 10.1158/1055-9965.EPI-07-2594 In this prospective study of postmenopausal women, we did not observe an inverse association between circulating 25(OH)D or 1,25(OH)2D and breast cancer risk, although we cannot exclude an association in younger women or with long-term or earlier exposure

Plasma 25-hydroxyvitamin D levels and risk of incident hypertension among young women. Forman JP, Curhan GC, Taylor EN. Hypertension. 2008 Nov;52(5):828-32. Epub 2008 Oct 6. PMID: 18838623 doi: 10.1161/HYPERTENSIONAHA.108.117630 Women in the lowest compared with highest quartile of plasma 25(OH)D had an adjusted odds ratio for incident hypertension of 1.66 (95% CI: 1.11 to 2.48; P for trend=0.01). Compared with women with sufficient levels, those with vitamin D deficiency (<30 ng/mL; 65.7% of the study population) had a multivariable odds ratio of 1.47 (95% CI: 1.10 to 1.97). Plasma 25(OH)D levels are inversely and independently associated with the risk of developing hypertension.

Evidence from clinical trials shows, with a wide margin of confidence, that a prolonged intake of 10,000IU/d of vitamin D3 poses no risk of adverse effects for adults, even if this is added to a rather high physiologic background level of vitamin D. Vitamin D and cancer mini-symposium: the risk of additional vitamin D. Vieth R.\nAnn Epidemiol. 2009 Jul;19(7):441-5. Epub 2009 Apr 11. PMID: 19364661 doi:10.1016/j.annepidem.2009.01.009

Meta-analysis: longitudinal studies of serum vitamin D and colorectal cancer risk. Yin L, Grandi N, Raum E, Haug U, Arndt V, Brenner H. Aliment Pharmacol Ther. 2009 Jul 1;30(2):113-25. Epub 2009 Apr 15. PMID: 19392870 DOI: 10.1111/j.1365-2036.2009.04022.x Conclusions Our results support suggestions that serum 25(OH)D is inversely related to CRC risk.

A prospective nested case-control study of vitamin D status and pancreatic cancer risk in male smokers. Stolzenberg-Solomon RZ, Vieth R, Azad A, Pietinen P, Taylor PR, Virtamo J, Albanes D. Cancer Res. 2006 Oct 15;66(20):10213-9. PMID: 17047087 doi: 10.1158/0008-5472.CAN-06-1876 Contrary to expectations, subjects with higher prediagnostic vitamin D status had an increased pancreatic cancer risk compared with those with lower status. Our findings need to be replicated in other populations and caution is warranted in their interpretation and implication. Our results are intriguing and may provide clues that further the understanding of the etiology of this highly fatal cancer.

Vitamin D and cancer mini-symposium: the risk of additional vitamin D. Vieth R. Ann Epidemiol. 2009 Jul;19(7):441-5. Epub 2009 Apr 11. Review. PMID: 19364661 Conclusion The results of well-conducted trials of vitamin D lead to the conclusion that the current U.S. National Academy of Sciences-Institute of Medicine upper limit for vitamin D intake of 2000IU per day 1, 37 is excessively conservative. That intake would raise serum 25(OH)D by an average of about 50 nmol/L (20 ng/mL), well within the safe range of serum 25(OH)D concentrations that extends to 500 nmol/L (200 ng/mL). Intake of 4,000IU per day would raise serum 25(OH)D by an average of about 100 nmol/L (40 ng/mL). Even prolonged physiologic-replacement intake of 10,000IU per day of vitamin D3 would pose no known risk of adverse effects in virtually all adults.

Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP. Am J Clin Nutr. 2007 Jun;85(6):1586-91. Erratum in: Am J Clin Nutr. 2008 Mar;87(3):794. PMID: 17556697 Conclusions: Improving calcium and vitamin D nutritional status substantially reduces all-cancer risk in postmenopausal women.

Vitamin D supplementation during the first year of life and risk of schizophrenia: a Finnish birth cohort study. McGrath J, Saari K, Hakko H, Jokelainen J, Jones P, Järvelin MR, Chant D, Isohanni M. Schizophr Res. 2004 Apr 1;67(2-3):237-45. PMID: 14984883 Conclusion: Vitamin D supplementation during the first year of life is associated with a reduced risk of schizophrenia in males. Preventing hypovitaminosis D during early life may reduce the incidence of schizophrenia.

Vitamin D, aging, and cancer. Tuohimaa P. Nutr Rev. 2008 Oct;66(10 Suppl 2):S147-52. Review. PMID: 18844842 DOI: 10.1111/j.1753-4887.2008.00095.x Deficiency of the prohormone calcidiol (25OH vitamin D3) seems to be associated with several aging-related chronic diseases including cancer. Our results suggest that calcidiol is mainly responsible for differentiation homeostasis, whereas calcitriol might be more involved in calcium homeostasis. Therefore, an imbalance of calcidiol rather than calcitriol is a risk factor for cancer and chronic diseases. Calcidiol insufficiency, as well as insufficient solar exposure, is associated with increased risk of several solid cancers. Both a vitamin D3 deficiency and a high concentration of calcidiol may increase cancer risk. Similarly, aging phenomena show a U-shaped association with vitamin D bioactivity. Therefore, the chronic diseases and cancers related to aging might be prevented by an optimal concentration of serum calcidiol, which remains to be determined.

Serum vitamin D and risk of prostate cancer in a case-control analysis nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). Travis RC, Crowe FL, Allen NE, Appleby PN, Roddam AW, Tjønneland A, Olsen A, Linseisen J, Kaaks R, Boeing H, Kröger J, Trichopoulou A, Dilis V, Trichopoulos D, Vineis P, Palli D, Tumino R, Sieri S, Bueno-de-Mesquita HB, van Duijnhoven FJ, Chirlaque MD, Barricarte A, Larrañaga N, González CA, Argüelles MV, Sánchez MJ, Stattin P, Hallmans G, Khaw KT, Bingham S, Rinaldi S, Slimani N, Jenab M, Riboli E, Key TJ. Am J Epidemiol. 2009 May 15;169(10):1223-32. Epub 2009 Apr 9. PMID: 19359375 In summary, the results of this large nested case-control study provide no evidence in support of a protective effect of circulating concentrations of vitamin D on the risk of prostate cancer.

Relationship between low ultraviolet B irradiance and higher breast cancer risk in 107 countries. Mohr SB, Garland CF, Gorham ED, Grant WB, Garland FC. Breast J. 2008 May-Jun;14(3):255-60. Epub 2008 Apr 17. PMID: 18422861 DOI: 10.1111/j.1524-4741.2008.00571.x There was a protective effect of UVB irradiance on risk of breast cancer that was independent of fertility rate, proportion of the population overweight, alcohol intake, animal energy intake, and other covariates.

Vitamin D and cardiovascular disease risk. Michos ED, Melamed ML. Curr Opin Clin Nutr Metab Care. 2008 Jan;11(1):7-12. Review. PMID: 18090651 doi: 10.1097/MCO.0b013e3282f2f4dd Summary: Vitamin D deficiency is easy to screen for and easy to treat with supplementation. Further larger observational studies and randomized clinical trials are, however, needed to determine whether vitamin D supplementation could have any potential benefit in reducing future cardiovascular disease events and mortality risk.

ncident invasive breast cancer, geographic location of residence, and reported average time spent outside. Millen AE, Pettinger M, Freudenheim JL, Langer RD, Rosenberg CA, Mossavar-Rahmani Y, Duffy CM, Lane DS, McTiernan A, Kuller LH, Lopez AM, Wactawski-Wende J. Cancer Epidemiol Biomarkers Prev. 2009 Feb;18(2):495-507. Epub 2009 Feb 3. PMID: 19190147 doi: 10.1158/1055-9965.EPI-08-0652 In conclusion, region of residence and geographic solar irradiance are not consistently related to risk of breast cancer and may not be sufficient proxy measures for sunlight/vitamin D exposure. The observed association between time spent outside and breast cancer risk support the hypothesis that vitamin D may protect against breast cancer.

Vitamin D Status and the Risk of Cardiovascular Disease Death. Kilkkinen A, Knekt P, Aro A, Rissanen H, Marniemi J, Heliövaara M, Impivaara O, Reunanen A. Am J Epidemiol. 2009 Sep 17. [Epub ahead of print] PMID: 19762371 doi:10.1093/aje/kwp227 A low vitamin D level may be associated with higher risk of a fatal CVD event, particularly cerebrovascular death. These findings need to be replicated in other populations. To demonstrate a causal link between vitamin D and CVD, randomized controlled trials are required.