Hypercalcemia, hypercalciuria, and kidney stones in long-term studies of vitamin D supplementation: a systematic review and meta-analysis.
Am J Clin Nutr. 2016 Sep 7. pii: ajcn134981
Malihi Z1, Wu Z1, Stewart AW1, Lawes CM1, Scragg R 2 r.scragg@auckland.ac.nz.
1School of Population Health, University of Auckland, Auckland, New Zealand.
2School of Population Health, University of Auckland, Auckland, New Zealand
BACKGROUND:Vitamin D supplementation is increasingly being used in higher doses in randomized controlled trials (RCTs). However, adverse events from very large annual doses of vitamin D have been shown in 2 RCTs, whereas in a third RCT, low-dose vitamin D, with calcium supplements, was shown to increase kidney stone risk.
OBJECTIVE:We analyzed the side effects related to calcium metabolism in RCTs, specifically hypercalcemia, hypercalciuria, and kidney stones, in participants who were given vitamin D supplements for =24 wk compared with in subjects in the placebo arm.
DESIGN:The following 3 main online databases were searched: Ovid Medline (PubMed), EMBASE, and the Cochrane Library. Software was used for the meta-analysis.
RESULTS:A total of 48 studies with 19,833 participants were identified, which reported =1 of the following side effects: hypercalcemia, hypercalciuria, or kidney stones. Of these studies, kidney stones were reported in only 9 trials with a tendency for fewer subjects reporting stones in the vitamin D arm than in the placebo arm (RR: 0.66, 95% CI: 0.41, 1.09; P = 0.10). In 37 studies, hypercalcemia was shown with increased risk shown for the vitamin D group (RR: 1.54; 95% CI: 1.09, 2.18; P = 0.01). Similar increased risk of hypercalciuria was shown in 14 studies for the vitamin D group (RR: 1.64; 95% CI: 1.06, 2.53; P = 0.03). In subgroup analyses, it was shown that the effect of vitamin D supplementation on risk of hypercalcemia, hypercalciuria, or kidney stones was not modified by baseline 25-hydroxyvitamin D, vitamin D dose and duration, or calcium co-supplementation.
CONCLUSIONS:Long-term vitamin D supplementation resulted in increased risks of hypercalcemia and hypercalciuria, which were not dose related. However, vitamin D supplementation did not increase risk of kidney stones. Additional large RCTs of long-term vitamin D supplementation are required to confirm these findings.
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