Is High Dose Vitamin D Harmful?
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ORIGINAL RESEARCH
Is High Dose Vitamin D Harmful? Kerrie M. Sanders • Geoffrey C. Nicholson Peter R. Ebeling
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Received: 7 February 2012 / Accepted: 15 November 2012 / Published online: 19 December 2012 Ó Springer Science+Business Media New York 2012
Abstract With the potential to minimize the risk of many chronic diseases and the apparent biochemical safety of ingesting doses of oral vitamin D several-fold higher than the current recommended intakes, recent research has focussed on supplementing individuals with intermittent, high-dose vitamin D. However, two recent randomized controlled trials (RCTs) both using annual high-dose vitamin D reported an increase, rather than a decrease, in the primary outcome of fractures. This review summarises the results from studies that have used intermittent, high doses of vitamin D, with particular attention to those finding evidence of adverse effects. Results from observational, population-based studies with evidence of a U- or J-shaped curve are also presented as these findings suggest an increased risk in those with the highest serum 25D levels. Speculative mechanisms are discussed and biochemical results from studies using high-dose vitamin D are also presented. Emerging evidence from both observational studies and RCTs suggests there should be a degree of caution about recommending high serum 25D concentrations for the entire population. Furthermore, benefit of the higher doses commonly used in clinical practice on falls risk reduction needs to be demonstrated. The safety of loading doses of vitamin D should be demonstrated before
The authors have stated that they have no conflict of interest. K. M. Sanders (&) G. C. Nicholson P. R. Ebeling Department of Medicine, Western Health, NorthWest Academic Centre, University of Melbourne, PO Box 294, St Albans, VIC 3021, Australia e-mail: [email protected] G. C. Nicholson Rural Clinical School, School of Medicine, University of Queensland, Toowoomba, QLD, Australia
these regimens become recommended as routine clinical practice. The current dilemma of defining vitamin D insufficiency and identifying safe and efficacious repletion regimens needs to be resolved. Keywords Steroid hormones Vitamin D Osteoporosis Fractures Age Aging
The need for vitamin D supplementation has evolved because it is widely recognized that a significant proportion of many populations has inadequate vitamin D status [1]. Serum 25-hydroxyvitamin D (25[OH]D) levels of 25 nmol/L or less are considered ‘‘deficient,’’ while the definition of ‘‘insufficiency’’ varies, with some experts regarding less than 50 nmol/L as the cut-off [2] and others considering less than 75 nmol/L as ‘‘insufficient’’ [3–5]. ‘‘Insufficient’’ in this review refers to 25(OH)D levels in the range 25–50 nmol/L, ‘‘intermittent’’ dosing refers to at least 1-week dosing intervals, and ‘‘high dose’’ refers to an intermittent bolus dose of at least 20,000 IU or a daily dose of 4,000 IU. Although the risk of many chronic disorders may be reduced by an upward shift in th
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