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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.

Dietary recommendations for vitamin D: a critical need for functional end points to establish an estimated average requirement. Whiting SJ, Calvo MS. J Nutr. 2005 Feb;135(2):304-9. Review. PMID: 15671232 In summary, vitamin D has emerged as a critical nutrient for which there is a compelling health need to establish adequate dietary guidelines in North America and worldwide given the increasing evidence of vitamin D deficiency and insufficient links to risk of chronic disease. We strongly argue that now there are enough data to consider setting an estimated average requirement for vitamin D and to recognize the crucial need for more research to determine the role of vitamin D in noncalciotropic functions and prevention of chronic diseases

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.

Pharmacokinetics of a single, large dose of cholecalciferol. Ilahi M, Armas LA, Heaney RP. Am J Clin Nutr. 2008 Mar;87(3):688-91. PMID: 1832660 Conclusions: Cholecalciferol (100 000 IU) is a safe, effective, and simple way to increase calcidiol concentrations. The dosing interval should be ≤2 mo to ensure continuous serum calcidiol concentrations above baseline. Our study highlights that 100 000 IU cholecalciferol is a safe, efficient, and cost-effective means to increase calcidiol concentrations in the elderly. From this study we can safely recommend 100 000 IU cholecalciferol dosed every 2 mo in persons with moderate baseline calcidiol concentrations. However, in those persons with baseline calcidiol concentrations < 20 ng/mL, even this large dose will not adequately raise their calcidiol concentrations.

The role of vitamin D in cancer prevention. Garland CF, Garland FC, Gorham ED, Lipkin M, Newmark H, Mohr SB, Holick MF. Am J Public Health. 2006 Feb;96(2):252-61. Epub 2005 Dec 27. Review. PMID: 16380576 DOI: 10.2105/AJPH.2004.045260 Vitamin D status differs by latitude and race, with residents of the northeastern United States and individuals with more skin pigmentation being at increased risk of deficiency. A PubMed database search yielded 63 observational studies of vitamin D status in relation to cancer risk, including 30 of colon, 13 of breast, 26 of prostate, and 7 of ovarian cancer, and several that assessed the association of vitamin D receptor genotype with cancer risk. The majority of studies found a protective relationship between sufficient vitamin D status and lower risk of cancer. The evidence suggests that efforts to improve vitamin D status, for example by vitamin D supplementation, could reduce cancer incidence and mortality at low cost, with few or no adverse effects

Serum 25-hydroxyvitamin D status of vegetarians, partial vegetarians, and nonvegetarians: the Adventist Health Study-2. Chan J, Jaceldo-Siegl K, Fraser GE. Am J Clin Nutr. 2009 May;89(5):1686S-1692S. Epub 2009 Apr 1. PMID: 19339396 Conclusions: s25(OH)D concentrations were not associated with vegetarian status. Other factors, such as vitamin D supplementation, degree of skin pigmentation, and amount and intensity of sun exposure have greater influence on s25(OH)D than does diet.

The role of vitamin D in cancer prevention. Garland CF, Garland FC, Gorham ED, Lipkin M, Newmark H, Mohr SB, Holick MF. Am J Public Health. 2006 Feb;96(2):252-61. Epub 2005 Dec 27. Review. PMID: 16380576 DOI: 10.2105/AJPH.2004.045260 Vitamin D status differs by latitude and race, with residents of the northeastern United States and individuals with more skin pigmentation being at increased risk of deficiency. A PubMed database search yielded 63 observational studies of vitamin D status in relation to cancer risk, including 30 of colon, 13 of breast, 26 of prostate, and 7 of ovarian cancer, and several that assessed the association of vitamin D receptor genotype with cancer risk. The majority of studies found a protective relationship between sufficient vitamin D status and lower risk of cancer. The evidence suggests that efforts to improve vitamin D status, for example by vitamin D supplementation, could reduce cancer incidence and mortality at low cost, with few or no adverse effects.

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.

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.

A longitudinal study of serum 25-hydroxyvitamin D and intact parathyroid hormone levels indicate the importance of vitamin D and calcium homeostasis regulation in multiple sclerosis. Soilu-Hänninen M, Laaksonen M, Laitinen I, Erälinna JP, Lilius EM, Mononen I. J Neurol Neurosurg Psychiatry. 2008 Feb;79(2):152-7. Epub 2007 Jun 19. PMID: 17578859 doi:10.1136/jnnp.2006.105320 Conclusions: The endocrine circuitry regulating serum calcium may be altered in MS. There is an inverse relationship between serum vitamin D level and MS clinical activity. The role of vitamin D in MS must be explored further.

Using these functional indicators, several studies have more accurately defined vitamin D deficiency as circulating levels of 25(OH)D ≤ 80 nmol or 32 µg/L. Recent studies reveal that current dietary recommendations for adults are not sufficient to maintain circulating 25(OH)D levels at or above this level, especially in pregnancy and lactation. Circulating 25-hydroxyvitamin D levels indicative of vitamin D sufficiency: implications for establishing a new effective dietary intake recommendation for vitamin D. Hollis BW. J Nutr. 2005 Feb;135(2):317-22. Review. PMID: 15671234 [

Evidence-based decision making on micronutrients and chronic disease: long-term randomized controlled trials are not enough. Ames BN, McCann JC, Stampfer MJ, Willett WC. Am J Clin Nutr. 2007 Aug;86(2):522-3; author reply 523-4. PMID: 17684228

Vitamin D status affects serum parathyroid hormone concentrations during winter in female adolescents: associations with forearm bone mineral density. Outila TA, Kärkkäinen MU, Lamberg-Allardt CJ. Am J Clin Nutr. 2001 Aug;74(2):206-10. PMID: 11470722 Conclusion: A large percentage of adolescent females have low vitamin D status during the winter in Finland, which seems to have negative effects on bone health.

Pharmacokinetics of vitamin D toxicity. Jones G. Am J Clin Nutr. 2008 Aug;88(2):582S-586S. Review. PMID: 18689406

Does nutritional intake differ between children with autism spectrum disorders and children with typical development? Herndon AC, Diguiseppi C, Johnson SL, Leiferman J, Reynolds A. J Autism Dev Disord. 2009 Feb;39(2):212-22. Epub 2008 Jul 4. PMID: 18600441 DOI: 10.1007/s10803-008-0606-2

Pittas AG, Lau J, Hu FB, Dawson-Hughes B. The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis. J Clin Endocrinol Metab. 2007 Jun;92(6):2017-29. Epub 2007 Mar 27. Review. PMID: 17389701 [PubMed - indexed for MEDL

M. F. McCarty and K. I. Block Toward a core nutraceutical program for cancer management. Integr Cancer Ther, June 1, 2006; 5(2): 150 - 171.

Reinehr T, de Sousa G, Alexy U, Kersting M, Andler W. Vitamin D status and parathyroid hormone in obese children before and after weight loss. Eur J Endocrinol. 2007 Aug;157(2):225-32. PMID: 17656603 [PubMed - in process]

Vieth R, Chan PC, MacFarlane GD. Efficacy and safety of vitamin D3 intake exceeding the lowest observedadverse effect level. Am J Clin Nutr. 2001 Feb;73(2):288-94. PMID: 11157326

Vitamin D in pregnancy and lactation: maternal, fetal, and neonatal outcomes from human and animal studies. Kovacs CS. Am J Clin Nutr. 2008 Aug;88(2):520S-528S. Review. PMID: 18689394 Dosing recommendations for women during pregnancy and lactation might be best directed toward ensuring that the neonate is vitamin D-sufficient and that this sufficiency is maintained during infancy and beyond. A dose of vitamin D that provides 25(OH)D sufficiency in the mother during pregnancy should provide normal cord blood concentrations of 25(OH)D. Research has shown that during lactation, supplements administered directly to the infant can easily achieve vitamin D sufficiency; the mother needs much higher doses (100 µg or 4000 IU per day) to achieve adult-normal 25(OH)D concentrations in her exclusively breastfed infant. In addition, the relation (if any) of vitamin D insufficiency in the fetus or neonate to long-term nonskeletal outcomes such as type 1 diabetes and other chronic diseases needs to be investigated.