Vitamin D Toxicity: A 16-Year Retrospective Study at an Academic Medical Center

John P. Lee, DO; Michael Tansey, MD; Jennifer G. Jetton, MD; Matthew D. Krasowski, MD, PhD


Lab Med. 2018;49(2):123-129. 

In This Article

Abstract and Introduction


Background Interest in vitamin D has increased during the past 2 decades, with a corresponding increase in laboratory testing of 25-hydroxyvitamin D [25(OH)D]. The vast majority of specimens tested display normal or deficient levels of 25(OH)D; concentrations rarely fall in the potentially toxic range.

Methods We performed a retrospective investigation of elevated 25(OH)D levels during a 16-year period at the University of Iowa Hospitals and Clinics (UIHC), a 734-bed tertiary-/quaternary-care academic medical center in the midwestern United States. Detailed medical-record review was performed for patients with serum/plasma 25(OH)D concentrations higher than 120 ng per mL.

Results A total of 127,932 serum/plasma 25(OH)D measurements were performed on 73,779 unique patients. Of these patients, 780 (1.05%) had results that exceeded 80 ng per mL and 89 patients (0.12%) had results that exceeded 120 ng per mL. Only 4 patients showed symptoms of vitamin D toxicity. Three of these cases involved inadvertent misdosing of liquid formulations.

Conclusions Symptomatic vitamin D toxicity is uncommon, and elevated levels of 25(OH)D do not strongly correlate with clinical symptoms or total serum/plasma calcium levels. Our study highlights the potential risks of the liquid formulation of vitamin D.


During the past 2 decades, interest in vitamin D has significantly increased, partly due to newly hypothesized connections of vitamin D to the immune system, cardiovascular health, and even cancer prevention.[1] Also, widespread recognition of vitamin D deficiency has prompted increased supplementation, to prevent important adverse health consequences such as osteoporosis.[2] We note that supplementation, in many cases, may be patient driven, rather than prescribed by physicians. Although evidence for the benefits of vitamin D supplementation is still emerging, the rate of its use has increased, along with a concomitant rise in vitamin D testing.[3] Despite that most test results are from patients with normal or deficient levels, the incidence of vitamin D toxicity has also risen.[4]

Vitamin D toxicity is poorly understood and not well defined in the literature.[5] Multiple commercial reference laboratories have varying cut-off values for the upper limit of normal for 25-hydroxyvitamin D [25(OH)D] levels. Further, potentially toxic levels of 25(OH)D have been shown to correlate poorly with hypercalcemia and symptomatic presentation. Vitamin D toxicity has been reported in multiple age groups and from multiple causes, including manufacturing errors, errors in milk fortification, incorrect dosing from liquid preparations, and intentional (although with no intent to harm) ingestion of megadoses of vitamin D supplements.[6–10] Among these causes, the most harmful appears to be sustained ingestion of megadoses (eg 50,000 IU) and incorrect dosing of supplements in children. We performed a medical-record review in patients with elevated 25(OH)D levels during a 16-year period at an academic medical center, in an effort to describe the causes of hypervitaminosis D and the extent to which vitamin D levels correlate with serum calcium levels and clinical symptoms.