Vitamin D supplementation associated with dose-response increase in hypercalciuria
Older adults assigned to a high dose of daily vitamin D supplementation were more likely to develop hypercalciuria over 3 years vs. those assigned to a lower daily dose of the supplement, with the condition resolving after reducing calcium intake, according to findings from the Calgary Vitamin D study presented at the American Society for Bone and Mineral Research Annual Meeting.
The Institute of Medicine set the tolerable upper intake level for vitamin D at 4,000 IU per day, Emma O. Billington, MD, FRCPC, clinical assistant professor in the division of endocrinology and metabolism at the University of Calgary in Alberta, Canada, and colleagues wrote in an abstract. More than 3% of U.S. adults report vitamin D intakes greater than 4,000 IU per day, they added, but the safety of this practice is unknown.
“Our study also suggests hypercalciuria may occur relatively frequently in a healthy population over a 3-year period,” Billington told Endocrine Today. “The 400 IU group essentially was following the Institute of Medicine’s recommended total daily intake for vitamin D and calcium.”
Billington and colleagues conducted a 3-year, double-blind, randomized controlled trial to investigate the dose-dependent effects of vitamin D supplementation on bone density and strength; safety was a prespecified secondary outcome.
The researchers analyzed data from 373 participants aged 55 to 70 years with a serum 25-hydroxyvitamin D level between 30 nmol/L and 125 nmol/L (mean age, 62 years; 52% women). Participants were randomly assigned to 400 IU, 4,000 IU or 10,000 IU vitamin D3 daily for 3 years. Calcium supplementation was initiated if dietary calcium intake was less than 1,200 mg per day. Researchers collected fasting blood samples at baseline and 3, 6, 12, 18, 24, 30 and 36 months to assess vitamin D and calcium levels.
Hypervitaminosis D was defined as 25-(OH)D more than 450 nmol/L; hypercalcemia as serum calcium more than 2.55 mmol/L. Hypercalciuria was defined as 24-hour urine calcium more than 7.5 mmol or more than 0.1 mmol/kg body if weight was more than 75 kg, measured at baseline, 12, 24 and 36 months. Calcium intake was reduced if hypercalciuria occurred. Researchers collected any adverse events, including fractures and falls, and used Fisher’s exact tests to examine relationships between categorical variables.
At 3 months, mean serum 25-(OH)D levels were 76 nmol/L in the 400-IU group, 114 nmol/L in the 4,000-IU group and 187 nmol/L in the 10,000-IU group, according to the abstract.
Incidence of hypercalcemia varied between the vitamin D groups, ranging from 0 in the 400-IU group to 3% and 9% in the 4,000 and 10,000 IU groups, respectively (P < .001).
Hypercalciuria occurred in 87 participants, including 17% in the 400-IU group, 22% in the 4,000-IU group and 31% in the 10,000-IU group (P = .04).
Researchers did not observe any cases of hypervitaminosis D during the study. Adverse events did not differ between groups.
The researchers noted that there was a dose-response increase in hypercalcemia which resolved on repeat testing, and hypercalciuria which usually resolved with reduction in calcium intake.
"Hypercalciuria is common in the general population, and the incidence appears to increase with higher vitamin D doses,” Billington said. “We recommend that clinicians and patients consider this when weighing the risks and benefits of high-dose vitamin D supplementation."
The results follow findings from a similar randomized controlled trial published online in Clinical Endocrinology in September and reported by Endocrine Today, which suggested that upper-limit intake for vitamin D recommended by the Endocrine Society, when coadministered with calcium intake at the upper recommended level, is associated with increased odds for hypercalciuria when compared against recommendations from the Institute of Medicine. In that study, healthy, white, postmenopausal women assigned to the high-dose vitamin D group were 3.6 times more likely to develop hypercalciuria vs. those in the lower-dose group (OR = 3.6; 95% CI, 1.39-9.3). There were no between-group differences for development of hypercalcemia and no between-group differences for adverse events. – by Regina Schaffer
Daly R, et al. Poster FRI-0824. Presented at: American Society for Bone and Mineral Research Annual Meeting; Sept. 28-Oct. 1, 2018; Montreal.
Disclosure: Billington reports she has received honoraria from Amgen unrelated to this study.