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Low vitamin D status, high bone turnover, and bone fractures in centenarians. Passeri G, Pini G, Troiano L, Vescovini R, Sansoni P, Passeri M, Gueresi P, Delsignore R, Pedrazzoni M, Franceschi C. J Clin Endocrinol Metab. 2003 Nov;88(11):5109-15. PMID: 14602735 We conclude that the extreme decades of life are characterized by a pathophysiological sequence of events linking vitamin D deficiency, low serum calcium, and secondary hyperparathyroidism with an increase in bone resorption and severe osteopenia. These data offer a rationale for the possible prevention of elevated bone turnover, bone loss, and consequently the reduction of osteoporotic fractures and fracture-induced disability in the oldest olds through the supplementation with calcium and vitamin D.

"Thursday, 17 December 2009 This blog is in response to Dr Briffa's post here. as I keep having problems commenting on his blogs. While 44ng/ml is sufficient to not only maximize uptake of calcium (>32ng/ml) and ensure maximum bone mineral density (>42ng/ml), pregnant and nursing mothers should be aware that in order to maximize the amount of vitamin D3 in human breast milk 6400iu/daily was found to be necessary to raise (>58ng/ml) at latitude 32. This is detailed in the Taylor, Wagner and Hollis paper. Vitamin D supplementation during lactation to support infant and mother. Although 4000iu/daily met the mothers daily needs in full it left babies being born with lower 25(OH)D status than required for optimum calcium absorption They also found DAILY use of supplements was required by pregnant and nursing mothers to ensure an even daily Vitamin D3 supply to the foetus & baby. It makes virtually no measurable difference for everyone else if you supplement daily or weekly. While Dr Briffa will not be lactating he may be interested seeing in the Grassrootshealth chart showing disease incidence by 25(OH)D status. this may encourage him to go just another 10ng/ml higher and a bit nearer to the natural level at which human breast milk flows replete with D3."

Barger-Lux MJ, Heaney RP. Effects of above average summer sun exposure on serum 25-hydroxyvitamin D and calcium absorption.J Clin Endocrinol Metab. 2002 Nov;87(11):4952-6.PMID: 12414856 [PubMed - indexed for MEDLINE]

25-Hydroxyvitamin D and functional outcomes in adolescents. Lamberg-Allardt CJ, Viljakainen HT. Am J Clin Nutr. 2008 Aug;88(2):534S-536S. Review. PMID: 18689396 CONCLUSIONS Cross-sectional studies have shown a relation among serum 25(OH)D concentration, serum PTH concentration, and BMD in adolescents. Long-term randomized controlled intervention studies have shown that vitamin D3 supplementation has a positive effect on BMD in adolescence; some of these studies found an effect with doses as small as 5 µg (200 IU) to 10 µg (400 IU) per day, or without supplemental calcium.

The second committee meeting was held August 4-5, 2009 in Washington, DC and included an Information-Gathering Workshop on August 4, 2009. The agenda for this workshop is below, along with the PowerPoint presentations that were used by the speakers during the workshop. Please note, online presentations from this meeting are subject to copyright protection. Permission from the speaker is required prior to any copying, reproducing, or rebroadcasting any portion of the speaker's presentations. Additional copyright and legal policies of The National Academies can be read in the National Academies Legal Statement.

Vitamin D intake is low and hypovitaminosis D common in healthy 9- to 15-year-old Finnish girls. Lehtonen-Veromaa M, Möttönen T, Irjala K, Kärkkäinen M, Lamberg-Allardt C, Hakola P, Viikari J. Eur J Clin Nutr. 1999 Sep;53(9):746-51. PMID: 10509773 CONCLUSION: Hypovitaminosis D is fairly common in growing Finnish girls in the wintertime, and three months of vitamin D supplementation with 10 microg/d was insufficient in preventing hypovitaminosis D. The daily dietary vitamin D intake was insufficient (< 5 microg/d) in the majority of participants, while the calcium intake was usually sufficient.

Parathyroid hormone, but not vitamin D, is associated with the metabolic syndrome in morbidly obese women and men: a cross-sectional study. Hjelmesaeth J, Hofsø D, Aasheim ET, Jenssen T, Moan J, Hager H, Røislien J, Bollerslev J. Cardiovasc Diabetol. 2009 Feb 3;8:7. PMID: 19187564 doi:10.1186/1475-2840-8-7 CONCLUSION: The PTH level, but not the vitamin D level, is an independent predictor of MS in treatment seeking morbidly obese Caucasian women and men. Randomized controlled clinical trials, including different therapeutic strategies to lower PTH, e.g. calcium/vitamin D supplementation and weight reduction, are necessary to explore any cause-and-effect relationship.

Strong correlations have been noted between cardiovascular diseases and low bone density / osteoporosis-connections so strong that the presence of one is considered a likely predictor of the other. This relationship has led to the hypothesis that these conditions share core pathophysiological mechanisms. Recent advances in our understanding of the complimentary roles played by vitamin D3 and vitamin K2 in vascular and bone health provide support for this hypothesis, along with insight into key metabolic dysfunctions underlying cardiovascular disease and osteoporosis. Part II, The Vitamin K Connection to Cardiovascular Health, reviews the ways in which vitamin K regulates calcium utlization, preventing vascular and soft tissue calcification while complimenting the bone-building actions of vitamin D, and also discusses vitamin K safety and dosage issues, and the necessity of providing vitamin K and vitamin A along with vitamin D to preclude adverse effects associated with hypervitaminosis D.

A multicountry ecologic study of risk and risk reduction factors for prostate cancer mortality. Grant WB. Eur Urol. 2004 Mar;45(3):271-9. PMID: 15036670 CONCLUSIONS: These results are consistent with insulin-like growth factor-I (IGF-I), being an important risk factor for prostate cancer, with alcohol and calcium being less important risk factors, and with allium family vegetables, and, to a lesser extent, vitamin D being important risk reduction factors. These results should provide guidance for additional studies on dietary and environmental links to prostate cancer.

Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis. Avenell A, Gillespie WJ, Gillespie LD, O'Connell D. Cochrane Database Syst Rev. 2009 Apr 15;(2):CD000227. Review. PMID: 19370554 DOI: 10.1002/14651858.CD000227.pub3 AUTHORS' CONCLUSIONS: Frail older people confined to institutions may sustain fewer hip fractures if given vitamin D with calcium. Vitamin D alone is unlikely to prevent fracture. Overall there is a small but significant increase in gastrointestinal symptoms and renal disease associated with vitamin D or its analogues. Calcitriol is associated with an increased incidence of hypercalcaemia.

This article discusses our experience at the one-day Institute of Medicine workshop on vitamin D and calcium. Both of us had an opportunity to make comments before the committee. Here are Paul's comments and slides and here are Amy's comments and slides. Note that our 2009 paper in Autoimmunity Reviews[1] discusses some of the science we allude to in further detail.

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.

Not enough vitamin D: health consequences for Canadians. Schwalfenberg G. Can Fam Physician. 2007 May;53(5):841-54. Review PMID: 17872747 Conclusion Low levels of VTD are considered a major public health problem in Canada, especially during the winter. Those with risk factors should be screened for low 25(OH)D levels and repletion therapy instituted if needed. Researchers have estimated that the oral dose of vitamin D3 to attain and maintain 25(OH)D levels >80 nmol/L is 2200 IU/d if baseline levels are 20 to 40 nmol/L, 1800 IU/d if levels are 40 to 60 nmol/L, and 1160 IU/d if levels are between 60 and 80 nmol/L.64 We need to ensure that patients have healthy blood levels of 25(OH)D to prevent levels of parathyroid hormone from rising and to maximize absorption of calcium, magnesium, and phosphate. Positive effects on bone are marginal at best unless patients consume at least 800 IU/d of VTD. The emerging and exciting role of the VTD receptor and the actions of VTD in maintaining health in other cell types have become more apparent during the last decade.

Upper levels of vitamin D intake were set at 50 microg/d (2000 IU/d) for all ages. Some individuals would require higher levels than these to achieve serum 25-hydroxyvitamin D concentrations for optimal calcium absorption. So much new information on vitamin D and health has been collected since the requirements were set in 1997 that this nutrient is likely the most in need of revised requirements. Vitamin D requirements: current and future. Weaver CM, Fleet JC. Am J Clin Nutr. 2004 Dec;80(6 Suppl):1735S-9S. Review. Erratum in: Am J Clin Nutr. 2005 Mar;81(3):729. PMID: 15585797

Low serum 25-hydroxyvitamin D concentrations and secondary hyperparathyroidism in middle-aged white strict vegetarians. Lamberg-Allardt C, Kärkkäinen M, Seppänen R, Biström H. Am J Clin Nutr. 1993 Nov;58(5):684-9. PMID: 8237875 In conclusion, white strict vegetarians are at risk of vitamin D deficiency, at least in the winter, primarily because of a low dietary vitamin D intake, despite a normal sunlight exposure in summer. Low serum 25(OH)D concentrations are accompanied by high S-iPTH concentrations, which also are affected by a low calcium intake. The effect of these changes on bone health remains to be evaluated.

Healthy elderly French women living at home have secondary hyperparathyroidism and high bone turnover in winter. EPIDOS Study Group. Chapuy MC, Schott AM, Garnero P, Hans D, Delmas PD, Meunier PJ. J Clin Endocrinol Metab. 1996 Mar;81(3):1129-33. PMID: 8772587 These results show that vitamin D status of a French aged population in good health and living at home depends mainly on lifestyle. Like institutionalized women, old women living at home exhibit clear evidence of senile hyperparathyroidism in the winter, secondary in part to a reduced 25OHD level and associated with biological signs of increased bone turnover. The maintenance of PTH within the normal range for healthy adults by vitamin D and calcium treatment might constitute an approach for the prevention of bone loss in the entire

Vitamin D and living in northern latitudes--an endemic risk area for vitamin D deficiency. Huotari A, Herzig KH. Int J Circumpolar Health. 2008 Jun;67(2-3):164-78. Review. PMID: 18767337 CONCLUSIONS: Vitamin D plays a fundamental role in calcium and phosphate homeostasis. A deficiency of vitamin D has been attributed to several diseases. Since its production in the skin depends on exposure to UVB-radiation via the sunlight, the level of vitamin D is of crucial importance for the health of inhabitants who live in the Nordic latitudes where there is diminished exposure to sunlight during the winter season. Therefore, fortification or supplementation of vitamin D is necessary for most of the people living in the northern latitudes during the winter season to maintain adequate levels of circulating 25(OH)D3 to maintain optimal body function and prevent diseases.

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

Suominen MH, Hosia Randell HM, Muurinen S, Peiponen A, Routasalo P, Soini H, Suur Uski I, Pitkala KH.