Hypercalcemia, hypercalciuria, and kidney stones in long-term studies of vitamin D supplementation: a systematic review and meta-analysis
Malihi Z, Wu Z, Stewart AW, Lawes CM, Scragg R
Published in American Journal of Clinical Nutrition
Methodology
Systematic review and meta-analysis searching Ovid Medline, EMBASE and the Cochrane Library for randomised controlled trials giving vitamin D for 24 weeks or longer and reporting hypercalcaemia, hypercalciuria or kidney stones versus placebo, with subgroup analyses by baseline vitamin D status, dose, duration and calcium co-supplementation.
Key Findings
This systematic review and meta-analysis pooled 48 randomised trials with 19,833 participants given vitamin D for at least 24 weeks. Vitamin D significantly increased the risk of high blood calcium (risk ratio 1.54, 95% CI 1.09 to 2.18, p = 0.01, 37 studies) and of high urinary calcium (RR 1.64, 95% CI 1.06 to 2.53, p = 0.03, 14 studies). Kidney stones, reported in only nine trials, were if anything less common with vitamin D (RR 0.66, 95% CI 0.41 to 1.09, p = 0.10). Subgroup analyses found these risks were not modified by baseline 25-hydroxyvitamin D, dose, duration or calcium co-supplementation.
Conclusions
Long-term vitamin D supplementation raised the risk of hypercalcemia and hypercalciuria but did not increase kidney stone risk.
Limitations
Adverse events were inconsistently reported across trials, with kidney stones captured in only nine of 48 studies, and the absence of a dose relationship is hard to reconcile with the biology; the authors call for additional large long-term trials.
Supplements Studied
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.
Related Health Concerns
Study Details
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This information is for educational purposes only. Always consult a healthcare professional before starting any supplement regimen.