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Vieth R. \nCritique of the considerations for establishing the tolerable upper intake level for vitamin D: critical need for revision upwards.\nJ Nutr. 2006 Apr;136(4):1117-22.\nPMID: 16549491 [PubMed - indexed for MEDLINE]

Measuring 25-hydroxyvitamin D in a clinical environment: challenges and needs. Hollis BW. Am J Clin Nutr. 2008 Aug;88(2):507S-510S. Review. PMID: 18689391 In this article, I provide an overview of the techniques available for measuring 25(OH)D, compare these techniques with one another, and assess their clinical utility. I also briefly discuss the stability of 25(OH)D in biological media and present an overview of the Vitamin D External Quality Assessment Scheme.

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Vitamin D and diabetes: improvement of glycemic control with vitamin D3 repletion. Schwalfenberg G. Can Fam Physician. 2008 Jun;54(6):864-6. PMID: 18556494 Conclusion These cases support information that is already known about VTD and its effect on the islet cell. As discussed above, this might be true only for vitamin D3 and not vitamin D2, although vitamin D2 has been shown to improve bone health. Vitamin D insufficiency or deficiency is common, and repletion might improve glycemic control early in type 2 diabetes. Diabetes is one of the fastest growing chronic diseases worldwide. Vitamin D3 is inexpensive and readily available. Well-designed clinical studies are required to ascertain if improving 25(OH)D levels from an insufficiency or deficiency to sufficiency improves glycemic control in diabetes. These studies need to be properly designed: a randomized controlled trial with VTD deficiency or insufficiency identified in diabetic patients of various ethnic

Annual intramuscular injection of a megadose of cholecalciferol for treatment of vitamin D deficiency: efficacy and safety data. Diamond TH, Ho KW, Rohl PG, Meerkin M. Med J Aust. 2005 Jul 4;183(1):10-2. PMID: 15992330 Conclusions: Once-yearly intramuscular cholecalciferol injection (600 000 IU) is effective therapy for vitamin D deficiency. While this therapy appears to be safe, the potential for developing hypercalciuria needs to be examined in a large randomised controlled trial.

Prevalence of Vitamin D inadequacy among postmenopausal North American women receiving osteoporosis therapy. Holick MF, Siris ES, Binkley N, Beard MK, Khan A, Katzer JT, Petruschke RA, Chen E, de Papp AE. J Clin Endocrinol Metab. 2005 Jun;90(6):3215-24. Epub 2005 Mar 29. PMID: 15797954 doi:10.1210/jc.2004-2364 Conclusions: More than half of North American women receiving therapy to treat or prevent osteoporosis have vitamin D inadequacy, underscoring the need for improved physician and public education regarding optimization of vitamin D status in this population.

Age-related changes in the 25-hydroxyvitamin D versus parathyroid hormone relationship suggest a different reason why older adults require more vitamin D. Vieth R, Ladak Y, Walfish PG. J Clin Endocrinol Metab. 2003 Jan;88(1):185-91. PMID: 12519850 This study shows that all age groups exhibit a high prevalence of 25(OH)D insufficiency and secondary hyperparathyroidism. Older adults are just as efficient in maintaining 25(OH)D, but they need more vitamin D to produce the higher 25(OH)D concentrations required to overcome the hyperparathyroidism associated with their diminishing renal function

Supplementation with cholecalciferol does not improve glycaemic control in diabetic subjects with normal serum 25-hydroxyvitamin D levels. Jorde R, Figenschau Y. Eur J Nutr. 2009 Apr 16. [Epub ahead of print] PMID: 19370371 10.1007/s00394-009-0020-3 Conclusions We were not able to demonstrate that vitamin D supplementation had a significant effect on glucose metabolism in subjects with type 2 diabetes but without vitamin D deficiency. Further studies are needed in larger groups of subjects with type 2 diabetes or impaired glucose tolerance, who also exhibit low serum 25-hydroxyvitamin D levels.

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.

Aging decreases the capacity of human skin to produce vitamin D3. MacLaughlin J, Holick MF. J Clin Invest. 1985 Oct;76(4):1536-8. PMID: 2997282 doi:10.1172/JCI112134 An evaluation of surgically obtained skin (age range, 8-92 yr) revealed that there is an age-dependent decrease in the epidermal concentrations of provitamin D3 (7-dehydrocholesterol). To ascertain that aging indeed decreased the capacity of human skin to produce vitamin D3, some of the skin samples were exposed to ultraviolet radiation and the content of previtamin D3 was determined in the epidermis and dermis. The epidermis in the young and older subjects was the major site for the formation of previtamin D3, accounting for greater than 80% of the total previtamin D3 that was produced in the skin. A comparison of the amount of previtamin D3 produced in the skin from the 8- and 18-yr-old subjects with the amount produced in the skin from the 77- and 82-yr-old subjects revealed that aging can decrease by greater than twofold the capacity of the skin to produce previtamin D3. Recognition of this difference may be extremely important for the elderly, who infrequently expose a small area of skin to sunlight and who depend on this exposure for their vitamin D nutritional needs.

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.

Vitamin D deficiency: a worldwide problem with health consequences. Holick MF, Chen TC. Am J Clin Nutr. 2008 Apr;87(4):1080S-6S. Review. PMID: 18400738 A reevaluation needs to take place of what the adequate intakes of vitamin D should be for children and adults. The literature over the past decade suggests that the Institute of Medicine recommendations in 1997 (83) are inadequate, and some experts including us suggest that both children and adults should take ≥800-1000 IU vitamin D/d from dietary and supplemental sources (4, 9, 77) when sunlight is unable to provide it. This recommendation, however, has not yet been embraced either by official government or pediatric organizations in the United States, Canada, or Europe for either children or adults.

Vitamin D status: measurement, interpretation, and clinical application. Holick MF. Ann Epidemiol. 2009 Feb;19(2):73-8. Epub 2008 Mar 10. Review. PMID: 18329892 Conclusion The only way to determine whether a person is vitamin D deficient or sufficient is to measure their circulating level of 25(OH)D. There are a variety of assays used to measure 25(OH)D. The radioimmunoassays and competitive protein binding assays for 25(OH)D are useful in detecting vitamin D deficiency and sufficiency. However, these assays are fraught with technical difficulties, especially if they are not run routinely (Fig. 4) (33). Several reference laboratories have now switched to LC-MS ,which measures both 25(OH)D2 and 25(OH)D3 quantitatively. The total 25(OH)D, i.e., 25(OH)D2 plus 25(OH)D3, is what physicians need to be aware of for their patients. A level >30 ng/mL is

An evaluation of the vitamin D3 content in fish: Is the vitamin D content adequate to satisfy the dietary requirement for vitamin D? Lu Z, Chen TC, Zhang A, Persons KS, Kohn N, Berkowitz R, Martinello S, Holick MF. J Steroid Biochem Mol Biol. 2007 Mar;103(3-5):642-4. Epub 2007 Jan 30. PMID: 17267210 doi: 10.1016/j.jsbmb.2006.12.010 Surprisingly, farmed salmon had approximately 25% of the vitamin D content as wild salmon had. The vitamin D content in fish varied widely even within species. These data suggest that the tables that list the vitamin D content are out-of-date and need to be re-evaluated. Little is known about the effect of cooking on the vitamin D content in fish. When farm salmon was baked, almost all of the vitamin D content, i.e. 240 IU of vitamin D3 was recovered from 3.5 oz. of salmon. The initial concentration in the uncooked salmon was 245 IU of vitamin D3. However, when the salmon was fried in vegetable oil, approximately 50% (123 IU of vitamin D3 was recovered.) We also evaluated the vitamin D content in mackerel which is traditionally considered to be an excellent source of vitamin D3 because of its oily content. However, in the one sample that we tested, we only observed 24 IU of vitamin D3 in 3.5 oz.

Serum 25-hydroxyvitamin D3 concentrations and carotid artery intima-media thickness among type 2 diabetic patients. Targher G, Bertolini L, Padovani R, Zenari L, Scala L, Cigolini M, Arcaro G. Clin Endocrinol (Oxf). 2006 Nov;65(5):593-7. PMID: 17054459 DOI: 10.1111/j.1365-2265.2006.02633.x CONCLUSIONS: Hypovitaminosis D is highly prevalent in type 2 diabetic adults and is strongly and independently associated with increased carotid IMT. Further investigation into whether vitamin D may play a role in the prevention of atherosclerosis appears to be warranted. In conclusion, our results show that type 2 diabetic adults have significant reductions in serum 25(OH)D concentrations (vs matched controls) that predict preclinical atherosclerosis, independent of classical risk factors, renal function tests, inflammatory markers, use of medications and presence of the metabolic syndrome. These findings suggest the need for ongoing evaluation of the possible protective role of vitamin D3 supplementation in the development of atherosclerosis.

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

Comment: The strengths of this randomized study include its high level of adherence and its use of a vitamin D dose sufficient to cause a biologically meaningful increase in serum levels. The adult daily value for vitamin D is 400 IU, but many U.S. women are vitamin-D-deficient (N Engl J Med 2007; 357:266). The Institute of Medicine considers doses up to 2000 IU to be without significant risk for adverse health effects. In addition to consuming dietary sources of vitamin D (see Table 1), most women will need supplements to achieve adequate intake. Multivitamins usually contain 400 IU of vitamin D.

Vitamin D and its role in skeletal muscle. Ceglia L. Curr Opin Clin Nutr Metab Care. 2009 Sep 18. [Epub ahead of print] PMID: 19770647 SUMMARY: Further studies are needed to fully characterize the underlying mechanisms of vitamin D action in human muscle tissue, to understand how these actions translate into changes in muscle cell morphology and improvements in physical performance, and to define the 25-hydroxyvitamin D level at which to achieve these beneficial effects in muscle.

Vitamin D treatment in multiple sclerosis. Myhr KM. J Neurol Sci. 2009 Jun 22. [Epub ahead of print] PMID: 19549608 doi:10.1016/j.jns.2009.05.002 Epidemiological evidence combined with clinical and laboratory analyses, and experimental animal models, suggest a possible influence of vitamin D on MS susceptibility as well as clinical disease activity. Supplement with vitamin D may reduce the risk of developing MS. An intervention may also reduce the risk of conversion from a first clinical event suggestive of MS to clinical definite MS, as well as reduce the relapse rate among patients with relapsing remitting MS. More studies are, however, needed to determine optimal dose and serum level for vitamin D, as well as target populations and optimal timing for intervention.