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Serum vitamin D concentration and prostate cancer risk: a nested case-control study. Ahn J, Peters U, Albanes D, Purdue MP, Abnet CC, Chatterjee N, Horst RL, Hollis BW, Huang WY, Shikany JM, Hayes RB; Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Project Team. J Natl Cancer Inst. 2008 Jun 4;100(11):796-804. Epub 2008 May 27. PMID: 18505967 doi:10.1093/jnci/djn152 CONCLUSION: The findings of this large prospective study do not support the hypothesis that vitamin D is associated with decreased risk of prostate cancer; indeed, higher circulating 25(OH)D concentrations may be associated with increased risk of aggressive disease. In summary, results from this large prospective study of men who underwent standardized prostate cancer screening in the context of a screening trial do not support the hypothesis that higher serum vitamin D status is associated with decreased risk of prostate cancer. The study showed no association of vitamin D level with nonaggressive disease; however, it raises the possibility that higher vitamin D level may be associated with increased risks for aggressive disease, although a clear monotonic dose-response relationship was lacking. Along with recent reports of adverse associations for higher vitamin D status and risk of pancreatic (32) and esophageal (33,34) cancer, caution should be taken in recommending high doses of vitamin D or sunlight exposure to the general public for prostate cancer prevention. Future analyses are warranted to confirm these results and to further clarify the effects of vitamin D on aggressive prostate cancer.

Improved cholecalciferol nutrition in rats is noncalcemic, suppresses parathyroid hormone and increases responsiveness to 1, 25-dihydroxycholecalciferol. Vieth R, Milojevic S, Peltekova V. J Nutr. 2000 Mar;130(3):578-84. PMID: 10702588 We conclude suppression of 1,25(OH)(2)D and PTH, and higher renal VDR mRNA and 24-hydroxylase did not involve higher free 1,25(OH)(2)D concentration or a first pass effect at the gut. Thus, 25(OH)D or a metabolite other than 1,25(OH)(2)D is a physiological, transcriptionally and biochemically active, noncalcemic vitamin D metabolite. When viewed from a perspective that starts with higher vitamin D nutrition, the results indicate that low vitamin D nutrition may bring about a form of resistance to 1,25(OH)2D. This situation would explain why, in humans, nutritional rickets and osteomalacia are commonly associated with normal or increased levels of 1,25(OH)2D (Chesney et al. 1981Citation , Eastwood et al. 1979Citation , Garabedian et al. 1983Citation ,Rasmussen et al. 1980Citation )-these are not like the low hormone levels associated with any other endocrine-deficiency disorder. A connection between lower vitamin D nutrition and vitamin D resistance helps to explain why the supposedly inactive compound 25(OH)D is more relevant in diagnosing nutritional rickets than is the active hormone 1,25(OH)2D. If the features of improved vitamin D nutrition shown here were demonstrated for any newly synthesized compound, the compound would be classified as a noncalcemic 1,25(OH)2D analogue (Brown et al. 1989Citation , Finch et al. 1999Citation , Goff et al. 1993Citation , Koshizuka et al. 1999Citation ). Thus, we contend that 25(OH)D or a metabolite of it other than 1,25(OH)2D exists as a physiological and biologically-active noncalcemic vitamin D metabolite whose effects require further examination, particularly in relationship to studies involving the synthetic analogs of 1,25(OH)2D.

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 Higher vitamin D concentrations were associated with a 3-fold increased risk for pancreatic cancer (highest versus lowest quintile, >65.5 versus <32.0 nmol/L: OR, 2.92; 95% CI, 1.56-5.48, Ptrend = 0.001) that remained after excluding cases diagnosed early during follow-up. 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. In conclusion, contrary to expectation, subjects with higher 25(OH)D concentrations were at greater risk for pancreatic cancer compared with those with lower concentrations in our prospective study with long-term follow-up. Caution is warranted in the interpretation and implication of our findings, however, as vitamin D inadequacy is an important public health problem and adequate status is desirable to prevent bone and other diseases (5). Our results, however, are intriguing and may provide clues that further the understanding of the etiology of this highly fatal cancer.

Prospective study of serum 25(OH)-vitamin D concentration and risk of oesophageal and gastric cancers. Chen W, Dawsey SM, Qiao YL, Mark SD, Dong ZW, Taylor PR, Zhao P, Abnet CC. Br J Cancer. 2007 Jul 2;97(1):123-8. Epub 2007 Jun 5. PMID: 17551495 We prospectively examined the relation between pretrial serum vitamin D status and risk of oesophageal and gastric cancers among subjects who developed cancer over 5.25 years of follow-up, including 545 oesophageal squamous cell carcinomas (ESCC), 353 gastric cardia adenocarcinomas, 81 gastric noncardia adenocarcinomas, and an age- and sex-stratified random sample of 1105 subjects. We found no associations for gastric cardia or noncardia adenocarcinoma. Among subjects with low vitamin D status, higher serum 25(OH)D concentrations were associated with significantly increased risk of ESCC in men, but not in women. Further refinements of the analysis did not suggest any factors, which could explain this unexpected result. In conclusion, we found a direct association between higher serum 25(OH)D concentration and increased risk of ESCC in men but not women in a large population-based prospective cohort study from rural China. We found no association with risk of gastric cardia or noncardia adenocarcinoma in either sex. Greater than 50% of our cohort had an inadequate serum 25(OH)D concentration, yet higher concentrations were associated with increased risk of ESCC compared to lower concentrations.

Serum 25(OH)-vitamin D concentration and risk of esophageal squamous dysplasia. Abnet CC, Chen W, Dawsey SM, Wei WQ, Roth MJ, Liu B, Lu N, Taylor PR, Qiao YL. Cancer Epidemiol Biomarkers Prev. 2007 Sep;16(9):1889-93. PMID: 17855710 doi: 10.1158/1055-9965.EPI-07-0461 Background: Squamous dysplasia is the precursor lesion for esophageal squamous cell carcinoma, and nutritional factors play an important role in the etiology of this cancer. Previous studies using a variety of measures for vitamin D exposure have reached different conclusions about the association between vitamin D and the risk of developing esophageal cancer. Conclusions: Higher serum 25(OH)D concentrations were associated with significantly increased risk of squamous dysplasia. No obvious source of measured or unmeasured confounding explains this finding. In conclusion, we found that a higher serum 25(OH)D concentration was associated with an increased risk of esophageal squamous dysplasia, the precursor lesion for ESCC. This finding concurs with our previous prospective study which found that higher vitamin D status was associated with increased risk of incident ESCC in this same population. These unexpected findings suggest that further studies of the association of vitamin D and digestive tract cancers are needed before the effect of vitamin D in different populations can be elucidated.

Optimal serum 25-hydroxyvitamin D levels for multiple health outcomes. Bischoff-Ferrari HA. Adv Exp Med Biol. 2008;624:55-71. Review. PMID: 18348447 DOI: 10.1007/978-0-387-77574-6_5 Recent evidence suggests that higher vitamin D intakes beyond current recommendations may be associated with better health outcomes. In this chapter, evidence is summarized from different studies that evaluate threshold levels for serum 25(OH)D levels in relation to bone mineral density (BMD), lower extremity function, dental health, risk of falls, admission to nursing home, fractures, cancer prevention and incident hypertension. For all endpoints, the most advantageous serum levels for 25(OH)D appeared to be at least 75 nmol/l (30 ng/ml) and for cancer prevention, desirable 25(OH)D levels are between 90-120 nmol/l (36-48 ng/ml). An intake of no less than 1000IU (25 meg) of vitamin D3 (cholecalciferol) per day for all adults may bring at least 50% of the population up to 75 nmol/l. Thus, higher doses of vitamin D are needed to bring most individuals into the desired range. While estimates suggest that 2000 IU vitamin D3 per day may successfully and safely achieve this goal, the implications of 2000 IU or higher doses for the total adult population need to be addressed in future studies.

"This website is about Vitamin D and MS Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS), with an uncertain cause. Colleen Hayes and Donald Achaeson have suggested that insufficient sunlight exposure and chronic viral infections might be unrelated environmental risk factors for MS. These risk factors may act synergistically to enable the pathogenic autoimmune response. The prevalence of MS is highest where environmental supplies of vitamin D are lowest. Sunshine enables the production of vitamin D3 (VD3) in the skin. Epidemiological studies have shown that higher vitamin D blood levels are associated with lower risk, less relapses and a slower progression of multiple sclerosis. Higher vitamin D levels can be achieved in part by increased oral intake of VD3. Optimal health requires serum 25 hydroxyvitamin D levels higher than 20 ng/ml (50 nmol/L) P Lips, 40 ng/ml (100 nmol/L) P Heaney or at least 40 ng/ml (100 nmol/L) R Vieth. "

Higher levels of 25-hydroxyvitamin D are associated with a lower incidence of multiple sclerosis only in women. Kragt J, van Amerongen B, Killestein J, Dijkstra C, Uitdehaag B, Polman Ch, Lips P. Mult Scler. 2009 Jan;15(1):9-15. Epub 2008 Aug 13. PMID: 18701572 DOI: 10.1177/1352458508095920 CONCLUSIONS: Our data suggest that higher circulating levels of 25(OH)D are associated with a lower incidence of MS and MS-related disability in women. This may imply clues to the pathogenesis of the sex difference in risk and to the nature of the environmental factors involved in MS.

"In a prospective study involving 6,937 men and women, higher levels of vitamin D were associated with a significantly lower risk of lung cancer in women and younger participants. During a maximum follow-up of 24 years, 122 cases of lung cancer were identified. After adjusting for potential confounders, higher serum 25-hydroxyvitamin D levels were associated with reduced risk of lung cancer risk in women (84% reduced risk) and younger participants (66% reduced risk). No association was observed between vitamin D status and lung cancer risk in men and older participants. "

Statins and vitamin D. Aloia JF, Li-Ng M, Pollack S. Am J Cardiol. 2007 Oct 15;100(8):1329. Epub 2007 Jul 5. No abstract available. PMID: 17920383 A total of 208 women were randomized to receive vitamin D3 (n=104) or placebo (n=104). 51 women were on statins. At baseline, the subjects on statins had a significantly higher 25-OHD level than the subjects who were not on statins (51.2 ± 20.1 nmol/L versus 43.2 ± 18.0 nmol/L respectively, p=0.008). This was also true when averaging 25-OHD levels across the 3-year study period and looking at active and placebo patients separately. 185 subjects had follow-up 25-OHD levels drawn every 6 months during the study. Higher levels were seen in the statin use subgroup whether they were on placebo or active vitamin D (Figure 1Figure 1). There was no interaction seen between vitamin D use and statin use, i.e. the impacts are additive (p=0.5502). This significant difference is comparable to the increase in 25-OHD levels seen in Pérez-Castrillón's study (41 ± 19 versus 47 ± 19 nmol/L, p=0.003) [1]. Although Pérez-Castrillón et al found a statistically significant relation between total cholesterol and 25-OHD (r=0.277, p=0.002), we did not find a significant relation between total cholesterol and 25-OHD in our study population.

How much vitamin D3 do the elderly need? Viljakainen HT, Palssa A, Kärkkäinen M, Jakobsen J, Lamberg-Allardt C. J Am Coll Nutr. 2006 Oct;25(5):429-35. PMID: 17031013 Conclusions: A clear dose response was noted in S-25-OHD to different doses of vitamin D3. The recommended dietary intake of 15 µg is adequate to maintain the S-25-OHD concentration around 40-55 nmol/L during winter, but if the optimal S-25-OHD is higher than that even higher vitamin D intakes are needed. Interestingly, subjects with lower vitamin D status at baseline responded more efficiently to supplementation than those with more adequate status

SSeason of diagnosis is a prognostic factor in Hodgkin's lymphoma: a possible role of sun-induced vitamin D. Porojnicu AC, Robsahm TE, Ree AH, Moan J. Br J Cancer. 2005 Sep 5;93(5):571-4. PMID: 16136030 doi:10.1038/sj.bjc.6602722 Epidemiological data for this period indicate that season of diagnosis is a strong prognostic factor for Hodgkin's lymphoma, with approximately 20% lower case fatality for patients diagnosed during autumn vs winter diagnosis (RR = 0.783, 95% CI,-0.62 to 0.99; P = 0.041). Notably, the improved autumnal survival rate was higher than 60% (RR = 0.364, 95% CI, -0.15 to 0.87; P = 0.025) for patients younger than 30 years. This finding may be related to higher endogenous levels of vitamin D in autumn, with a favourable influence on the conventional therapy. In conclusion, we have found that the prognosis of Hodgkin's lymphoma is significantly correlated with the season of diagnosis, particularly for patients younger than 30 years. This seasonal effect is presumably due to the vitamin D3 synthesis in skin during sun exposure. The present findings should encourage further investigations of the possible adjuvant role of vitamin D derivatives in cancer therapy

Serum 25-hydroxyvitamin D levels and the prevalence of peripheral arterial disease: results from NHANES 2001 to 2004. Melamed ML, Muntner P, Michos ED, Uribarri J, Weber C, Sharma J, Raggi P. Arterioscler Thromb Vasc Biol. 2008 Jun;28(6):1179-85. Epub 2008 Apr 16. PMID: 18417640 doi: 10.1161/ATVBAHA.108.165886 Conclusions- Low serum 25(OH)D levels are associated with a higher prevalence of PAD. Several mechanisms have been invoked in the literature to support a potential antiatherosclerotic activity of vitamin D. Prospective cohort and mechanistic studies should be designed to confirm this association. Vitamin D is an inhibitor of the renin-angiotensin system and has antiinflammatory and anticoagulant properties. Among 4839 NHANES 2001 to 2004 participants, low 25(OH)D levels were associated with a higher prevalence of PAD, after multivariate adjustment. To confirm this association, longitudinal cohort and mechanistic studies are needed.

Broe KE, Chen TC, Weinberg J, Bischoff-Ferrari HA, Holick MF, Kiel DP. \nA higher dose of vitamin d reduces the risk of falls in nursing home residents: a randomized, multiple-dose study.\nJ Am Geriatr Soc. 2007 Feb;55(2):234-9.\nPMID: 17302660 [PubMed -

"Under year round UV exposure conditions (low latitudes, broken line, "High UV") there is no association between 25(OH)D and either prostate or pancreatic cancer. At high latitudes (Solid line, "Low UV") there is a positive association between blood levels of 25(OH)D and these cancers. The average year round levels of 25(OH)D actually tend to be higher in northern latitudes, higher than those where there is year-round solar UVB. Vieth explains that we know almost nothing about the enzymes controlling tissue 1,25(OH)2D levels and much of his discussion is extrapolated from renal enzyme activity."

Benefits of Vitamin D Supplementation Joel M. Kauffman, Ph.D. Journal of American Physicians and Surgeons Volume 14 Number 2 - Summer 2009 Clinical trials show that vitamin D supplementation at higher levels than previously recommended is beneficial for many conditions. It decreases the frequency of falls and fractures, helps prevent cardiovascular disease, and reduces symptoms of colds or influenza. Benefits are also seen in diabetes mellitus, multiple sclerosis, Crohn disease, pain, depression, and possibly autism. Sunlight does not cause an overdose of vitamin D production, and toxicity from supplementation is rare. Dose recommendations are increasing, but appear to be lagging the favorable trial results. A number of common drugs deplete vitamin D levels, and others may limit its biosynthesis from sunlight. People with adequate levels from sun exposure will not benefit from supplementation. While dietary intake is helpful, supplementation is better able to raise serum 25-hydroxyvitamin D , the major circulating metabolite, to the level now thought adequate, 30-50 ng/mL. Where there is inadequate daily sun exposure, oral doses of 1,000-2,000 IU/d are now considered routine, with much higher doses (up to 50,000 IU) for rapid repletion now considered safe.

"We are aware of substantial scientific evidence supporting the role of vitamin D in prevention of cancer. It has been reasonably established that adequate serum vitamin D metabolite levels are associated with substantially lower incidence rates of several types of cancer, including those of the breast, colon, and ovary, and other sites. We have concluded that the vitamin D status of most individuals in North America will need to be greatly improved for substantial reduction in incidence of cancer. Epidemiological studies have shown that higher vitamin D levels are also associated with lower risk of Type I diabetes in children and of multiple sclerosis. Several studies have found that markers of higher vitamin D levels are associated with lower incidence and severity of influenza and several other infectious diseases."

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.

"DALLAS, Jan. 8 - The same vitamin D deficiency that can result in weak bones now has been associated with an increased risk of cardiovascular disease, Framingham Heart Study researchers report in Circulation: Journal of the American Heart Association. "Vitamin D deficiency is associated with increased cardiovascular risk, above and beyond established cardiovascular risk factors," said Thomas J. Wang, M.D., assistant professor of medicine at Harvard Medical School in Boston, Mass. "The higher risk associated with vitamin D deficiency was particularly evident among individuals with high blood pressure." In a study of 1,739 offspring from Framingham Heart Study participants (average age 59, all Caucasian), researchers found that those with blood levels of vitamin D below15 nanograms per milliliter (ng/mL) had twice the risk of a cardiovascular event such as a heart attack, heart failure or stroke in the next five years compared to those with higher levels of vitamin D."

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. Tuohimaa P, Tenkanen L, Ahonen M, Lumme S, Jellum E, Hallmans G, Stattin P, Harvei S, Hakulinen T, Luostarinen T, Dillner J, Lehtinen M, Hakama M. Int J Cancer. 2004 Jan 1;108(1):104-8. PMID: 14618623 DOI: 10.1002/ijc.11375