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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.

Serum 25-hydroxyvitamin D concentration and subsequent risk of type 2 diabetes. Mattila C, Knekt P, Männistö S, Rissanen H, Laaksonen MA, Montonen J, Reunanen A. Diabetes Care. 2007 Oct;30(10):2569-70. Epub 2007 Jul 12. PMID: 17626891 doi: 10.2337/dc07-0292 We found a significant inverse association between serum 25OHD and risk of type 2 diabetes in the simple model. However, the association was attenuated in the multivariate analysis, adjusting for potential risk factors of type 2 diabetes. To our knowledge, this is the first cohort study investigating the association between serum 25OHD and incidence of type 2 diabetes. Our results are in line with those from the Nurses' Health Study (5), where an inverse association was observed for the intake of vitamin D supplements. We could not differentiate whether the results depended on the effect of vitamin D deficiency on β-cell function or on insulin resistance. In summary, the results are in line with the hypothesis that a high serum 25OHD concentration may reduce the risk of type 2 diabetes. Further research is needed to confirm the association and to distinguish between the independent role of vitamin D and the role of healthy dietary and lifestyle patterns in reducing the risk of type 2 diabetes.

Summary of evidence-based review on vitamin D efficacy and safety in relation to bone health. Cranney A, Weiler HA, O'Donnell S, Puil L. Am J Clin Nutr. 2008 Aug;88(2):513S-519S. Review. PMID: 18689393 We found inconsistent evidence of an association between serum 25-hydroxyvitamin D [25(OH)D] concentration and bone mineral content in infants and fair evidence of an association with bone mineral content or density in older children and older adults. The evidence of an association between serum 25(OH)D concentration and some clinical outcomes (fractures, performance measures) in postmenopausal women and older men was inconsistent, and the evidence of an association with falls was fair. We found good evidence of a positive effect of consuming vitamin D-fortified foods on 25(OH)D concentrations. The evidence for a benefit of vitamin D on falls and fractures varied. We found fair evidence that adults tolerated vitamin D at doses above current dietary reference intake levels, but we had no data on the association between long-term harms and higher doses of vitamin D.

Differences in vitamin D status between countries in young adults and the elderly. McKenna MJ. Am J Med. 1992 Jul;93(1):69-77. PMID: 1385673 PURPOSE: To compare vitamin D status between countries in young adults and in the elderly. MATERIALS AND METHODS: Reports on vitamin D status (as assessed by serum 25-hydroxyvitamin D) from 1971 to 1990 were reviewed. Studies were grouped according to geographic regions: North America (including Canada and the United States); Scandinavia (including Denmark, Finland, Norway, and Sweden); and Central and Western Europe (including Belgium, France, Germany, Ireland, The Netherlands, Switzerland, and the United Kingdom). RESULTS: Vitamin D status varies with the season in young adults and in the elderly, and is lower during the winter in Europe than in both North America and Scandinavia. Oral vitamin D intake is lower in Europe than in both North America and Scandinavia. Hypovitaminosis D and related abnormalities in bone chemistry are most common in elderly residents in Europe but are reported in all elderly populations. CONCLUSIONS: The vitamin D status in young adults and the elderly varies widely with the country of residence. Adequate exposure to summer sunlight is the essential means to ample supply, but oral intake augmented by both fortification and supplementation is necessary to maintain baseline stores. All countries should adopt a fortification policy. It seems likely that the elderly would benefit additionally from a daily supplement of 10 micrograms of vitamin D.

Use of vitamin D in clinical practice. Cannell JJ, Hollis BW. Altern Med Rev. 2008 Mar;13(1):6-20. PMID: 18377099 The recent discovery--from a meta-analysis of 18 randomized controlled trials--that supplemental cholecalciferol (vitamin D) significantly reduces all-cause mortality emphasizes the medical, ethical, and legal implications of promptly diagnosing and adequately treating vitamin D deficiency. Not only are such deficiencies common, and probably the rule, vitamin D deficiency is implicated in most of the diseases of civilization. Vitamin D's final metabolic product is a potent, pleiotropic, repair and maintenance, seco-steroid hormone that targets more than 200 human genes in a wide variety of tissues, meaning it has as many mechanisms of action as genes it targets. One of the most important genes vitamin D up-regulates is for cathelicidin, a naturally occurring broad-spectrum antibiotic. Natural vitamin D levels, those found in humans living in a sun-rich environment, are between 40-70 ng per ml, levels obtained by few modern humans. Assessing serum 25-hydroxy-vitamin D (25(OH)D) is the only way to make the diagnosis and to assure treatment is adequate and safe. Three treatment modalities exist for vitamin D deficiency: sunlight, artificial ultraviolet B (UVB) radiation, and vitamin D3 supplementation. Treatment of vitamin D deficiency in otherwise healthy patients with 2,000-7,000 IU vitamin D per day should be sufficient to maintain year-round 25(OH)D levels between 40-70 ng per mL. In those with serious illnesses associated with vitamin D deficiency, such as cancer, heart disease, multiple sclerosis, diabetes, autism, and a host of other illnesses, doses should be sufficient to maintain year-round 25(OH)D levels between 55 -70 ng per mL. Vitamin D-deficient patients with serious illness should not only be supplemented more aggressively than the well, they should have more frequent monitoring of serum 25(OH)D and serum calcium. Vitamin D should always be

Vitamin D and breast cancer. Bertone-Johnson ER. Ann Epidemiol. 2009 Jul;19(7):462-7. Epub 2009 Feb 20. Review. PMID: 19230714 Though the relationship between vitamin D and breast cancer remains unclear, a growing body of evidence suggests that vitamin D may modestly reduce risk. A large number of in vitro studies indicate that vitamin D can inhibit cell proliferation and promote apoptosis and cell differentiation in breast tumor tissue. Results from analytic studies of sunlight exposure and dietary intake have been inconsistent but together generally support a modestly protective role of vitamin D, at least in some population subgroups. Studies using blood vitamin D metabolites to assess vitamin D status may be less prone to misclassification than those of diet and sunlight exposure. Overall, the two prospective and four case-control studies of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D tend to support a protective effect in older women. The relationship between common vitamin D receptor polymorphisms and risk remains unclear. Many questions about this relationship clearly remain, including the utility of assessing vitamin D through diet and sunlight exposure, the relationship between plasma metabolites, and the potential modifying effects of age, menopausal status and tumor characteristics. Given that vitamin D status is modifiable, additional prospective studies are necessary to determine if vitamin D may have important potential for breast cancer prevention.

Effects of Atorvastatin on vitamin D levels in patients with acute ischemic heart disease. Pérez-Castrillón JL, Vega G, Abad L, Sanz A, Chaves J, Hernandez G, Dueñas A. Am J Cardiol. 2007 Apr 1;99(7):903-5. Epub 2007 Feb 8. PMID: 17398180 In conclusion, atorvastatin increases vitamin D levels. This increase could explain some of the beneficial effects of atorvastatin at the cardiovascular level that are unrelated to cholesterol levels. The mechanism by which atorvastatin increases vitamin D levels is related to inhibition of 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase. Cholesterol is synthesized from 7-dehydrocholesterol, which is also a precursor of vitamin D3. For this reason, we initially observed a statistically significant relation between total cholesterol and vitamin D. HMG-CoA enzyme reductase is key to the synthesis of cholesterol, whereas ultraviolet radiation causes the formation of 25-hydroxyvitamin D. Inhibition of the enzyme may increase levels of 7-dehydrocholesterol and increase the synthesis of 25-hydroxycholecalciferol, thereby increasing vitamin D levels,10 although we observed no relation between lower cholesterol and increased vitamin D. In addition, 25-hydroxyvitamin D has been shown to inhibit HMG-CoA enzyme reductase activity in in vitro studies.11 A greater concentration of vitamin D could increase enzymatic inhibition, acting in synergy with the statin in decreasing total cholesterol.

Prospective study of serum vitamin D and cancer mortality in the United States. Freedman DM, Looker AC, Chang SC, Graubard BI. J Natl Cancer Inst. 2007 Nov 7;99(21):1594-602. Epub 2007 Oct 30. PMID: 17971526 doi:10.1093/jnci/djm204 CONCLUSIONS: Our results do not support an association between 25(OH)D and total cancer mortality, although there was an inverse relationship between 25(OH)D levels and colorectal cancer mortality.

PLYMOUTH medical researchers have discovered a link between lack of the 'sunshine vitamin' and the onset of dementia.\n\nTeams from the city's Peninsula Medical School and the universities of Cambridge and Michigan have for the first time found a relationship between lower Vitamin D levels and cognitive impairment in older people.\n\nThe results of their large-scale study are to be published in the Journal of Geriatric Psychology and Neurology.

"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."

Vitamin D and mood disorders among women: an integrative review. Murphy PK, Wagner CL. J Midwifery Womens Health. 2008 Sep-Oct;53(5):440-6. Review. PMID: 18761297 Four of six studies reviewed imparted significant results, with all four showing an association between low 25(OH)D levels and higher incidences of four mood disorders: premenstrual syndrome, seasonal affective disorder, non-specified mood disorder, and major depressive disorder. This review indicates a possible biochemical mechanism occurring between vitamin D and mood disorders affecting women, warranting further studies of these variables using rigorous methodologies.

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-hydroxyvitamin D levels in vitamin D-insufficient hip fracture patients after supplementation with ergocalciferol and cholecalciferol. Glendenning P, Chew GT, Seymour HM, Gillett MJ, Goldswain PR, Inderjeeth CA, Vasikaran SD, Taranto M, Musk AA, Fraser WD. Bone. 2009 Nov;45(5):870-5. Epub 2009 Jul 23. PMID: 19631774 doi:10.1016/j.bone.2009.07.015 Cholecalciferol supplementation resulted in a 31% greater increase in total HPLC-measured 25OHD (p=0.010) and 52% greater rise in RIA-measured 25OHD (p0.05). In vitamin D-insufficient hip fracture patients, supplementation with cholecalciferol 1000 IU/day for three months was more effective in increasing serum 25OHD than an equivalent dose of ergocalciferol. However, the lack of difference in PTH lowering between calciferol treatments raises questions about the biological importance of this observation.

Vitamin D-Related Changes in Physical Performance: A Systematic Review. Annweiler C, Schott AM, Berrut G, Fantino B, Beauchet O. J Nutr Health Aging. 2009;13(10):893-898. PMID: 19924350 Conclusions: The findings show that the association between vitamin D and physical performance remains controversial. Observational studies and clinical trials yielded divergent results, which highlights the complex and to date still poorly understood association between serum vitamin D concentration or vitamin D supplementation and physical performance.

Association between serum 25(OH)D concentrations and bone stress fractures in Finnish young men. Ruohola JP, Laaksi I, Ylikomi T, Haataja R, Mattila VM, Sahi T, Tuohimaa P, Pihlajamäki H. J Bone Miner Res. 2006 Sep;21(9):1483-8. doi: 10.1359/jbmr.060607 Conclusions: A lower level of serum 25(OH)D concentration may be a generally predisposing element for bone stress fractures. Considering the obvious need of additional vitamin D in prevention of stress fractures, the effects of vitamin D fortification of foods and supplementation will be subjects of interest for future research PMID: 16939407

Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. Ginde AA, Mansbach JM, Camargo CA Jr. Arch Intern Med. 2009 Feb 23;169(4):384-90. PMID: 19237723 Conclusions Serum 25(OH)D levels are inversely associated with recent URTI. This association may be stronger in those with respiratory tract diseases. Randomized controlled trials are warranted to explore the effects of vitamin D supplementation on RTI.

Association between plasma 25-hydroxyvitamin D and breast cancer risk. Crew KD, Gammon MD, Steck SE, Hershman DL, Cremers S, Dworakowski E, Shane E, Terry MB, Desai M, Teitelbaum SL, Neugut AI, Santella RM. Cancer Prev Res (Phila Pa). 2009 Jun;2(6):598-604. Epub 2009 May 26. PMID: 19470790 In summary, these results add to a growing body of evidence that adequate vitamin D stores may prevent breast cancer development. Whereas circulating 25-OHD levels of >32 ng/mL are associated with normal bone mineral metabolism, our data suggest that the optimal level for breast cancer prevention is ≥40 ng/mL. Well-designed clinical trials are urgently needed to determine whether vitamin D supplementation is effective for breast cancer chemoprevention.

Relationship between serum 25-hydroxyvitamin d and pulmonary function in the third national health and nutrition examination survey. Black PN, Scragg R. Chest. 2005 Dec;128(6):3792-8. PMID: 16354847

Association between serum 25(OH)D and death from prostate cancer. Tretli S, Hernes E, Berg JP, Hestvik UE, Robsahm TE. Br J Cancer. 2009 Feb 10;100(3):450-4. Epub 2009 Jan 20. PMID: 19156140 doi:10.1038/sj.bjc.6604865 The serum level of 25(OH)D may be involved in disease progression and is a potential marker of prognosis in patients with prostate cancer.

Association between serum 25-hydroxyvitamin D and depressive symptoms in Japanese: analysis by survey season A Nanri, T Mizoue, Y Matsushita, K Poudel-Tandukar, M Sato, M Ohta, N Mishima European Journal of Clinical Nutrition (19 August 2009) doi:10.1038/ejcn.2009.96 Short Communication