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Vitamin D response reduced if taken with Calcium – meta-analysis Oct 2015

Effect of Vitamin D or Activated Vitamin D on Circulating 1,25-Dihydroxyvitamin D Concentrations: A Systematic Review and Metaanalysis of Randomized Controlled Trials

Armin Zittermann1,*, Jana B. Ernst1, Ingvild Birschmann2 and Marcus Dittrich3,4
1 Clinic for Thoracic and Cardiovascular Surgery and
2 Institute for Laboratory and Transfusion Medicine, Heart and Diabetes Center North Rhine-Westphalia, Ruhr University Bochum, Bad Oeynhausen, Germany;
3 Department of Bioinformatics, Biocenter, University of Wuerzburg, Wuerzburg, Germany;
4 Institute of Human Genetics, University of Wuerzburg, Wuerzburg, Germany.
↵* Address correspondence to this author at: Clinic for Thoracic and Cardiovascular Surgery Heart and Diabetes Centre NRW, Georgstr. 11, D-32545 Bad Oeynhausen, Germany. Fax +49–5731-972020; e-mail azittermann at hdz-nrw.de.

BACKGROUND: Evidence is accumulating that circulating 1,25-dihydroxyvitamin D [1,25(OH)2D] concentrations are inversely related to overall mortality.

METHODS: We searched PubMed, Embase and ISI Web of Science for randomized controlled trials with a control group receiving a placebo instead of vitamin D/activated vitamin D and performed a metaanalysis to evaluate the effect of oral vitamin D/activated vitamin D on circulating 1,25(OH)2D concentrations using a random effects model.

RESULTS: We included 52 vitamin D intervention groups (4796 individuals) and 14 intervention groups with activated vitamin D (668 individuals). Vitamin D supplements increased circulating 1,25(OH)2D by 12.2 pmol/L (95% CI, 7.8–16.5 pmol/L) and 18.8 pmol/L (95% CI, 9.2–28.4 pmol/L) if only studies with a low risk of bias in study design and reporting were considered (n = 18). There was significant heterogeneity among studies (Cohran's Q P < 0.001, I2 = 91%). The incremental effect was larger in studies using vitamin D alone compared with coadministration of calcium supplements (18.6 pmol/L; 95% CI, 12.7–24.4 pmol/L vs 4.9 pmol/L; 95% CI, −0.4 to 10.2 pmol/L; P = 0.001), and if quantification was performed with RIA vs other methods (17.1 pmol/L; 95% CI, 11.1–23.1 pmol/L vs 6.9 pmol/L; 95% CI, 1.0–12.8 pmol/L; P = 0.02). Activated vitamin D increased the mean circulating 1,25(OH)2D by 20.5 pmol/L (95% CI, 8.3–32.7 pmol/L; P = 0.04). Again, there was evidence for significant heterogeneity among studies (Cochran Q = 85.4; P < 0.001; I2 = 87%), but subgroup analysis did not identify parameters significantly influencing the increment in 1,25(OH)2D concentrations.

CONCLUSIONS: Both vitamin D and activated vitamin D significantly increase circulating 1,25(OH)2D concentrations, but in vitamin D users this increase is suppressed by calcium coadministration.

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