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25-hydroxyvitamin D levels and the risk of mortality in the general population. Melamed ML, Michos ED, Post W, Astor B. Arch Intern Med. 2008 Aug 11;168(15):1629-37. PMID: 18695076 Conclusion The lowest quartile of 25(OH)D level (<17.8 ng/mL) is independently associated with all-cause mortality in the general population.

Hypovitaminosis D in British adults at age 45 y: nationwide cohort study of dietary and lifestyle predictors. Hyppönen E, Power C. Am J Clin Nutr. 2007 Mar;85(3):860-8. PMID: 17344510 Conclusion: Prevalence of hypovitaminosis D in the general population was alarmingly high during the winter and spring, which warrants action at a population level rather than at a risk group level. Data from the 1958 birth cohort suggest that, at different cutoffs for hypovitaminosis D, a substantial public health problem exists in British whites. Obese participants and those living in Scotland were at the highest risk of hypovitaminosis D. However, the prevalence in the general population was very high during the winter and spring, which suggests that, to improve the situation, action is required at a population level rather than at a risk-group level. In the United States, calls have gone out for an increase in vitamin D fortification of foods (11), and the data from the current study suggest that such action is also warranted in the United Kingdom. Vitamin D is currently available without prescription as a dietary supplement only as part of cod liver oil or multivitamin products; hence, a need clearly exists to consider increased availability of over-the-counter supplements. Hypovitaminosis D has been implicated in the development of serious conditions, including diabetes, various types of cancer, and cardiovascular diseases, in addition to its essential role in maintaining bone health (1, 2). The high rates of hypovitaminosis D reported in this study suggest that immediate action is needed to improve the vitamin D status of the British population.

Chatfield SM, Brand C, Ebeling PR, Russell DM. Vitamin D deficiency in general medical inpatients in summer and winter. Intern Med J. 2007 Jun;37(6):377-82. PMID: 17535381 [PubMed - in process]

Overview of general physiologic features and functions of vitamin D. DeLuca HF. Am J Clin Nutr. 2004 Dec;80(6 Suppl):1689S-96S. Review. PMID: 15585789

25-hydroxyvitamin D levels and the risk of mortality in the general population. Melamed ML, Michos ED, Post W, Astor B. Arch Intern Med. 2008 Aug 11;168(15):1629-37. PMID: 18695076

Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. Trivedi DP, Doll R, Khaw KT. BMJ. 2003 Mar 1;326(7387):469. PMID: 12609940 CONCLUSION: Four monthly supplementation with 100 000 IU oral vitamin D may prevent fractures without adverse effects in men and women living in the general community.

Hypovitaminosis D in medical inpatients. Thomas MK, Lloyd-Jones DM, Thadhani RI, Shaw AC, Deraska DJ, Kitch BT, Vamvakas EC, Dick IM, Prince RL, Finkelstein JS. N Engl J Med. 1998 Mar 19;338(12):777-83. PMID: 9504937 Conclusions Hypovitaminosis D is common in general medical inpatients, including those with vitamin D intakes exceeding the recommended daily amount and those without apparent risk factors for vitamin D deficiency.

Nutrients, endpoints, and the problem of proof. Heaney RP. 2008 W. O. Atwater Memorial Lecture J Nutr. 2008 Sep;138(9):1591-5. PMID: 18716155 To sum up, I think that there would be general agreement to the effect that nutrition is important, despite the fact that the still growing number of failed trials of individual nutrients might suggest that no nutrient actually made much of a difference, a conclusion that is absurd on its face and ought to have alerted us to the possibility that there was something wrong with how we were investigating the matter. To provide the proof needed to sustain revised intake recommendations, we shall have to find a design better suited to nutrients than the randomized controlled trial as currently implemented, and we need to develop a series of global indices, nutrient by nutrient, which better capture the polyvalent nature of most nutrients. Perhaps it would be useful for the ASN, in collaboration with concerned governmental entities such as the USDA, to convene a workshop to address these structural issues. Such deliberation may well be arduous and frustrating, but it is terribly important and, in my view, well worth the effort.

Vitamin D and type 2 diabetes: are we ready for a prevention trial? Scragg R. Diabetes. 2008 Oct;57(10):2565-6. PMID: 18820212 doi: 10.2337/db08-0879 Despite evidence from the current article (3) and the Finnish study (17), doubts still remain about whether low vitamin status is a cause of type 2 diabetes. Further cohort studies are required, assessing baseline vitamin D status using blood 25(OH)D to be sure that the Ely and Finnish studies are not false-positive results. Glucose clamp studies are also required because we are still not sure of the mechanism influenced by vitamin D-whether it is insulin resistance, secretion, or both. But most importantly, given that nearly three decades have passed since the first studies linking vitamin D with insulin metabolism (6,7), well-designed clinical trials of the effect of vitamin D supplementation on glycemia status and diabetes risk are urgently required to settle this question. And they need to prevent past mistakes. In particular, the vitamin D dose given in such trials needs to be high enough-above 2,000 IU per day (19)-to raise blood 25(OH)D levels above 80 nmol/l because diabetes risk is lowest at this level (9,20). If well-designed trials are carried out and confirm a protective effect from vitamin D, it could be used by the general population as a simple and cheap solution to help prevent the diabetes epidemic.

Vitamin D in preventive medicine: are we ignoring the evidence? Zittermann A. Br J Nutr. 2003 May;89(5):552-72. Review. PMID: 12720576 Vitamin D is metabolised by a hepatic 25-hydroxylase into 25-hydroxyvitamin D (25(OH)D) and by a renal 1alpha-hydroxylase into the vitamin D hormone calcitriol. Calcitriol receptors are present in more than thirty different tissues. Apart from the kidney, several tissues also possess the enzyme 1alpha-hydroxylase, which is able to use circulating 25(OH)D as a substrate. Serum levels of 25(OH)D are the best indicator to assess vitamin D deficiency, insufficiency, hypovitaminosis, adequacy, and toxicity. European children and young adults often have circulating 25(OH)D levels in the insufficiency range during wintertime. Elderly subjects have mean 25(OH)D levels in the insufficiency range throughout the year. In institutionalized subjects 25(OH)D levels are often in the deficiency range. There is now general agreement that a low vitamin D status is involved in the pathogenesis of osteoporosis. Moreover, vitamin D insufficiency can lead to a disturbed muscle function. Epidemiological data also indicate a low vitamin D status in tuberculosis, rheumatoid arthritis, multiple sclerosis, inflammatory bowel diseases, hypertension, and specific types of cancer. Some intervention trials have demonstrated that supplementation with vitamin D or its metabolites is able: (i) to reduce blood pressure in hypertensive patients; (ii) to improve blood glucose levels in diabetics; (iii) to improve symptoms of rheumatoid arthritis and multiple sclerosis. The oral dose necessary to achieve adequate serum 25(OH)D levels is probably much higher than the current recommendations of 5-15 microg/d.

Calcium and vitamin d supplementation decreases incidence of stress fractures in female navy recruits. Lappe J, Cullen D, Haynatzki G, Recker R, Ahlf R, Thompson K. J Bone Miner Res. 2008 May;23(5):741-9. PMID: 18433305 doi: 10.1359/jbmr.080102 Conclusions: Generalizing the findings to the population of 14,416 women who entered basic training at the Great Lakes during the 24 mo of recruitment, calcium and vitamin D supplementation for the entire cohort would have prevented 187 persons from fracturing. Such a decrease in SFx would be associated with a significant decrease in morbidity and financial costs.

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

Prevalence and Associations of 25-Hydroxyvitamin D Deficiency in US Children: NHANES 2001-2004. Kumar J, Muntner P, Kaskel FJ, Hailpern SM, Melamed ML. Pediatrics. 2009 Aug 3. [Epub ahead of print] PMID: 19661054 CONCLUSIONS: 25(OH)D deficiency is common in the general US pediatric population and is associated with adverse cardiovascular risks.

Vitamin D intake is inversely associated with rheumatoid arthritis: results from the Iowa Women's Health Study. Merlino LA, Curtis J, Mikuls TR, Cerhan JR, Criswell LA, Saag KG; Iowa Women's Health Study. Arthritis Rheum. 2004 Jan;50(1):72-7. PMID: 14730601 DOI: 10.1002/art.11434 CONCLUSION: Greater intake of vitamin D may be associated with a lower risk of RA in older women, although this finding is hypothesis generating.

A new study by researchers at the University of Colorado Denver and Massachusetts General Hospital (MGH) shows vitamin D plays a vital role in reducing the risk of death associated with older age. The research, just published in the Journal of the American Geriatrics Society, evaluated the association between vitamin D levels in the blood and the death rates of those 65 and older. The study found that older adults with insufficient levels of vitamin D die from heart disease at greater rates that those with adequate levels of the vitamin.

Clinical Responses to a Mega-dose of Vitamin D3 in Infants and Toddlers With Vitamin D Deficiency Rickets. Soliman AT, El-Dabbagh M, Adel A, Ali MA, Aziz Bedair EM, Elalaily RK. J Trop Pediatr. 2009 Jun 8. [Epub ahead of print] PMID: 19506025 doi:10.1093/tropej/fmp040 Conclusion: An IM injection of a mega dose of cholecalciferol is a safe and effective therapy for treatment of VDD rickets in infants and toddlers with normalization of all the biochemical parameters and healing of radiological manifestations. Measurement of serum 25(OH)D level is highly recommended in all short children with a clear need for a general vitamin D supplementation for all infants and young children in Qatar.

Current impediments to acceptance of the ultraviolet-B-vitamin D-cancer hypothesis. Grant WB, Boucher BJ. Anticancer Res. 2009 Sep;29(9):3597-604. PMID: 19667154 The ultraviolet-B (UVB)-vitamin D-cancer hypothesis was proposed in 1980. There have been numerous ecological, observational and other studies of the hypothesis. There are about 14 types of cancer for which it seems to apply: bladder, breast, colon, endometrial, esophageal, gallbladder, gastric, ovarian, pancreatic, rectal, renal and vulvar cancer and both Hodgkin's and non-Hodgkin's lymphoma. Nonetheless, the hypothesis has not yet been accepted by public health agencies. Some of the reasons for this include a distrust of ecological studies, some mistrust of observational studies, and the existence of just one positive randomized controlled trial, an analysis of a vitamin D and calcium supplementation study involving post-menopausal women in Nebraska. Paradigm shifts such as this generally take time, in part due to opposition from those content with the status quo. In this paper, results of ecological studies in the United States using summertime solar UVB as the index of vitamin D production, which is highly asymmetrical with respect to latitude, and indices for other cancer risk-modifying factors (air pollution, alcohol consumption, dietary iron and zinc, ethnic background, socioeconomic status, smoking and urban/rural residence) are discussed in terms of supporting the hypothesis. These studies were not considered while other ecological studies were examined in recent critiques of the hypothesis. While additional randomized controlled trials would, of course, be helpful, the current evidence seems to satisfy the criteria for causality as outlined by A. Bradford Hill.

The prevalence of hypovitaminosis D among US adults: data from the NHANES III. Zadshir A, Tareen N, Pan D, Norris K, Martins D. Ethn Dis. 2005 Autumn;15(4 Suppl 5):S5-97-101. PMID: 16315387 CONCLUSION: Serum levels of 25(OH) D3 are below the recommended levels for a large portion of the general adult population and in most minorities. Need exists for a critical review and probable revision of current recommendations for adult vitamin D intake to maintain adequate 25(OH) D3 levels.

Epidemiology of vitamin D insufficiency and cancer mortality. Pilz S, Tomaschitz A, Obermayer-Pietsch B, Dobnig H, Pieber TR. Anticancer Res. 2009 Sep;29(9):3699-704. Review. PMID: 19667167 In conclusion, we still need further studies to evaluate the association of vitamin D insufficiency and cancer incidence and mortality, but the multiple health benefits of vitamin D and the easy, safe and inexpensive way by which vitamin D can be supplemented should already guide current public health strategies to achieve 25(OH)D levels of at least 75 nmol/l (30 ng/ml) in the general population.

An estimated 50% to 60% of older people have suboptimal vitamin D levels, which is a problem that could affect more than bone health. Recent cross-sectional studies have also shown an association between low vitamin D levels and cardiovascular disease, hypertension, and metabolic syndrome. In a long-term prospective study from Germany, researchers assessed whether 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels were associated with all-cause and cardiovascular mortality among more than 3000 consecutive patients (mean age, 62) referred for coronary angiography.