When co-administered with calcium supplements, the safe upper level of vitamin D recommended by the Endocrine Society can result in frequent hypercalciuria, according to study results published in Clinical Endocrinology.

In this randomized, double-blind trial, researchers compared the incidence rates of hypercalciuria and hypercalcemia in female patients taking daily doses of calcium supplements and high or low levels of vitamin D. The 66 participants (average age, 61.5) in the first group were administered 1200 mg/day of calcium carbonate plus 10,000 IU/day of vitamin D3 and 66 participants in the second group received 1200 mg/day of calcium carbonate plus 400 IU/day of vitamin D3.

Over 1 year, participants were evaluated every 3 months for the development of hypercalcemia and hypercalciuria. Baseline characteristics were similar in both groups.

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Of the 47 individuals in the high-dose vitamin D group who completed the trial, 34 developed hypercalciuria at least once, 15 participants developed the condition 2 to 3 times, and 5 were hypercalciuric 4 times. Of the 45 individuals in the low vitamin D group who completed the trial, 19 developed hypercalciuria at least once, 7 developed hypercalciuria 2 to 3 times, and 2 were hypercalciuric 4 times. Via mixed effects logistic regression modeling, the researchers determined that the odds of developing hypercalciuria over time were 3.6 times greater in the high-dose vitamin D group than the low-dose vitamin D group (95% CI, 1.39-9.3).

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As for hypercalcemia, 23% of participants in the high-dose group developed the condition at least once compared with 17% in the low-dose group. There was not a significant time and group interaction term, indicating that the odds of developing hypercalcemia were no greater in the high-dose group than the low-dose group (P =.772).

The researchers noted certain limitations of their study such as its small sample size, which could hinder the ability to generalize to a broader population.

“Until further large scale studies are performed the [upper limit] for vitamin D proposed by the [Institute of Medicine] is to be preferred to that proposed by the Endocrine Society,” said the researchers, adding, “The [upper limit] for calcium intake should also be reexamined.”


Aloia JF, Katumuluwa S, Stolberg A, et al. Safety of calcium and vitamin d supplements, a randomized controlled trial [published online September 4, 2018]. Clinical Endocrinology. doi:10.1111/cen.13848

This article originally appeared on Endocrinology Advisor