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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.

25-hydroxyvitamin D levels inversely associate with risk for developing coronary artery calcification. de Boer IH, Kestenbaum B, Shoben AB, Michos ED, Sarnak MJ, Siscovick DS. J Am Soc Nephrol. 2009 Aug;20(8):1805-12. Epub 2009 May 14. PMID: 19443637 doi: 10.1681/ASN.2008111157 "In conclusion, lower 25-hydroxyvitamin D concentrations associate with increased risk for incident CAC. Accelerated development of atherosclerosis may underlie, in part, the increased cardiovascular risk associated with vitamin D deficiency."

Vitamin D status and the risk of lung cancer: a cohort study in Finland. Kilkkinen A, Knekt P, Heliövaara M, Rissanen H, Marniemi J, Hakulinen T, Aromaa A. Cancer Epidemiol Biomarkers Prev. 2008 Nov;17(11):3274-8. PMID: 18990771v In conclusion, although there was no overall association between vitamin D and lung cancer risk, women and young participants with a higher level of vitamin D were observed to have a lower lung cancer risk. Although experimental data support the suppressing effect of vitamin D on the development of lung cancer, large epidemiologic studies from different populations with repeated measurements of vitamin D are warranted to confirm this finding. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3274-8)

Diagnosis and treatment of vitamin D deficiency. Cannell JJ, Hollis BW, Zasloff M, Heaney RP. Expert Opin Pharmacother. 2008 Jan;9(1):107-18. PMID: 18076342 The recent discovery - in a randomised, controlled trial - that daily ingestion of 1100 IU of colecalciferol (vitamin D) over a 4-year period dramatically reduced the incidence of non-skin cancers makes it difficult to overstate the potential medical, social and economic implications of treating vitamin D deficiency. Not only are such deficiencies common, probably the rule, vitamin D deficiency stands implicated in a host of diseases other than cancer. The metabolic product of vitamin D is a potent, pleiotropic, repair and maintenance, secosteroid hormone that targets > 200 human genes in a wide variety of tissues, meaning it has as many mechanisms of action as genes it targets. A common misconception is that government agencies designed present intake recommendations to prevent or treat vitamin D deficiency. They did not. Instead, they are guidelines to prevent particular metabolic bone diseases. Official recommendations were never designed and are not effective in preventing or treating vitamin D deficiency and in no way limit the freedom of the physician - or responsibility - to do so. At this time, assessing serum 25-hydroxy-vitamin D is the only way to make the diagnosis and to assure that treatment is adequate and safe. The authors believe that treatment should be sufficient to maintain levels found in humans living naturally in a sun-rich environment, that is, > 40 ng/ml, year around. Three treatment modalities exist: sunlight, artificial ultraviolet B radiation or supplementation. All treatment modalities have their potential risks and benefits. Benefits of all treatment modalities outweigh potential risks and greatly outweigh the risk of no treatment. As a prolonged 'vitamin D winter', centred on the winter solstice, occurs at many temperate latitudes, ≤ 5000 IU (125 μg) of vitamin D/d

Vitamin D and calcium insufficiency-related chronic diseases: molecular and cellular pathophysiology. Peterlik M, Cross HS. Eur J Clin Nutr. 2009 Dec;63(12):1377-86. Epub 2009 Sep 2. PMID: 19724293 doi:10.1038/ejcn.2009.105 A compromised vitamin D status, characterized by low 25-hydroxyvitamin D (25-(OH)D) serum levels, and a nutritional calcium deficit are widely encountered in European and North American countries, independent of age or gender. Both conditions are linked to the pathogenesis of many degenerative, malignant, inflammatory and metabolic diseases. Studies on tissue-specific expression and activity of vitamin D metabolizing enzymes, 25-(OH)D-1alpha-hydroxylase and 25-(OH)D-24-hydroxylase, and of the extracellular calcium-sensing receptor (CaR) have led to the understanding of how, in non-renal tissues and cellular systems, locally produced 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) and extracellular Ca2+ act jointly as key regulators of cellular proliferation, differentiation and function. Impairment of cooperative signalling from the 1,25-(OH)2D3-activated vitamin D receptor (VDR) and from the CaR in vitamin D and calcium insufficiency causes cellular dysfunction in many organs and biological systems, and, therefore, increases the risk of diseases, particularly of osteoporosis, colorectal and breast cancer, inflammatory bowel disease, insulin-dependent diabetes mellitus type I, metabolic syndrome, diabetes mellitus type II, hypertension and cardiovascular disease. Understanding the underlying molecular and cellular processes provides a rationale for advocating adequate intake of vitamin D and calcium in all populations, thereby preventing many chronic diseases worldwide.

Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Hyppönen E, Läärä E, Reunanen A, Järvelin MR, Virtanen SM. Lancet. 2001 Nov 3;358(9292):1500-3. PMID: 11705562 doi:10.1016/S0140-6736(01)06580-1 INTERPRETATION: Dietary vitamin D supplementation is associated with reduced risk of type 1 diabetes. Ensuring adequate vitamin D supplementation for infants could help to reverse the increasing trend in the incidence of type 1 diabetes.

An ecologic study of dietary and solar ultraviolet-B links to breast carcinoma mortality rates. Grant WB. Cancer. 2002 Jan 1;94(1):272-81. PMID: 11815987 CONCLUSIONS It is hypothesized that animal products are associated with risk for breast carcinoma because they are associated with greater amounts of insulin-like growth factor-1and lifetime doses of estrogen. Vegetable products contain several risk reduction components including antioxidants and phytoestrogens. The association with latitude is very likely because of solar UV-B radiation and vitamin D. Alcohol modulates estrogen's effects on breasts. Fish intake is associated with risk reduction through vitamin D and n-3 oils. These results are consistent with those of many case-control and cohort studies but should be assessed in well designed cohort studies.

25-hydroxyvitamin D and risk of myocardial infarction in men: a prospective study. Giovannucci E, Liu Y, Hollis BW, Rimm EB. Arch Intern Med. 2008 Jun 9;168(11):1174-80. PMID: 18541825 Conclusion Low levels of 25(OH)D are associated with higher risk of myocardial infarction in a graded manner, even after controlling for factors known to be associated with coronary artery disease.

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.

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 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.