Vitamin D supplementation: upper limit for safety revisited?

Vitamin D overdosing includes hypercalcemia, hypercalciuria, and mineral deposits in soft tissues. A safety upper limit of 4000 IU/day, which is consistently accepted, has been challenged, since the risk of adverse events in other systems than calcium-phosphate homeostasis may depend not only on the dose, but on the outcome, the treatment regimen, and possibly the age, sex and vitamin D status. The therapeutic window of vitamin D supplementation may be narrower than hitherto recognized. The prevention and/or correction of vitamin D deficiency/insufficiency with 800-1000 IU/daily of vitamin D or 10 mu g/day of calcifediol are safe. Because of their potential harm, larger doses given on the long term or in intermittent regimens should not be selected.