Monthly high-dose vitamin D supplementation does not increase kidney stone risk or serum calcium: results from a randomized controlled trial.

Population-based, double-blind, placebo-controlled randomized trial in adults aged 50-84 years living in Auckland, New Zealand. The vitamin D arm had a mean age of 65.9 ± 8.3 years, 40.9% women, and was predominantly European/other (83.2%).

Monthly oral vitamin D3 100,000 IU was given as identical-looking soft-gel capsules containing sunflower oil, with 2 capsules in the first month and then 1 capsule monthly thereafter. Capsules were mailed monthly until June 2013 and every 4 months from July 2013; the comparator was identical placebo capsules.

Monthly 100,000 IU vitamin D3 did not increase kidney stone events or hypercalcemia compared with placebo over a median follow-up of 3.3 years. Kidney stone events occurred in 76 vitamin D participants versus 82 placebo participants, with HR 0.90 (95% CI: 0.66, 1.23; P = 0.51). Hospitalizations for urolithiasis were also not increased (7 vitamin D vs 11 placebo; HR 0.62, 95% CI: 0.24, 1.26; P = 0.30). In the annual blood-test subsample, there was no hypercalcemia in the vitamin D arm, and mean serum calcium rose from 2.28 at baseline to 2.36 at year 3 with no significant time-by-treatment effect (β = 0.005; SE = 0.003; P = 0.14).

Hypercalcemia assessment was limited to an annual blood-test subsample, and calcium-related events were rare. The low number of urolithiasis events reduces precision, especially for subgroup analyses by baseline 25(OH)D status. Findings are most directly applicable to community-dwelling adults aged 50-84 years in Auckland, New Zealand.