Prevalence of hypercalcemia related to hypervitaminosis D in clinical practice

Clin Nutr. 2016 Dec;35(6):1354-1358. doi: 10.1016/j.clnu.2016.02.017. Epub 2016 Mar 8.


Background & aims: Recent interest in vitamin D has led to a substantial increase in the use of vitamin D supplements. Vitamin D intoxication may be a concern as hypervitaminosis D can result in irreversible calcification of soft tissues so that it is important to detect early markers of vitamin D intoxication. Our aim was to assess the simultaneous presence of biochemical markers of vitamin D toxicity (i.e. hypervitaminosis D, hypercalcemia) and determine the concentrations of 25-OH-vitamin D at which the risk of hypercalcemia, and thus toxicity, might begin.

Methods: We evaluated retrospectively a 6-year period during which 25.567 samples were assessed for 25-OH-vitamin D status by UHPLC. Hypervitaminosis D was defined at serum 25-OH-vitamin D >160 nmol/L. Serum and urine calcium, phosphorus and iPTH were also recorded, if available. Medical history revision was performed in subjects displaying simultaneously hypervitaminosis D and hypercalcemia.

Results: Overall, hypervitaminosis D was found in 475 samples (1.86%) of which 51 displayed hypercalcemia (11.1%). A total of 382 samples were identified as the first record of hypervitaminosis D and 39 presented hypercalcemia (10.2%), most of them at 25-OH-vitamin D levels between 161 and 375 nmol/L. Only in 15 subjects, hypercalcemia could be directly attributed to vitamin D and serum 25-OH-vitamin D ranged between 164 and 1139 nmol/l. In no case, serum calcium achieved concentrations considered as critical values (>13 mg/dl).

Conclusion: Hypercalcemia due to vitamin D represented <4% of the total hypervitaminosis D detected and <0.1% of the tests performed. However, a highly variable response was observed and most subjects presented hypercalcemia at serum concentrations of 25-OH-vitamin D < 375 nmol/L.

Keywords: Clinical practice; Hipervitaminosis D; Hypercalcemia; Vitamin D status; Vitamin D toxicity.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Calcium / blood
  • Chromatography, High Pressure Liquid
  • Female
  • Humans
  • Hypercalcemia / blood
  • Hypercalcemia / epidemiology*
  • Male
  • Middle Aged
  • Reference Values
  • Retrospective Studies
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood
  • Vitamin D / toxicity*


  • Biomarkers
  • Vitamin D
  • 25-hydroxyvitamin D
  • Calcium