Vitamin D toxicity is rare. It is caused by supplementing with high doses of vitamin D rather than sunlight. The threshold for vitamin D toxicity has not been established; however, according to some research:
* 100μg/day (4k IU), have been show to not cause toxic levels. ages 9–71
* 240 μg/day (10k IU), over 5 months have been show not to cause toxicity.
* 1250μg/day (50k IU) over several months can increase serum 25-hydroxyvitamin D levels to 150ng/mL.
Those with certain medical conditions, such as primary hyperparathyroidism, are far more sensitive to vitamin D and develop hypercalcemia in response to any increase in vitamin D nutrition, while maternal hypercalcemia during pregnancy may increase fetal sensitivity to effects of vitamin D and lead to a syndrome of intellectual disability and facial deformities.
Idiopathic infantile hypercalcemia is caused by a mutation of the CYP24A1 gene, leading to a reduction in the degradation of vitamin D. Infants who have such a mutation have an increased sensitivity to vitamin D and in case of additional intake a risk of hypercalcaemia. The disorder can continue into adulthood.
A review published in 2015 noted that adverse effects have been reported only at 25(OH)D serum concentrations above 200nmol/L.
Published cases of toxicity involving hypercalcemia in which the vitamin D dose and the 25-hydroxy-vitamin D levels are known all involve an intake of ≥40,000IU (1,000μg) per day.
Those who are pregnant or breastfeeding should consult a doctor before taking a vitamin D supplement. The FDA advised manufacturers of liquid vitamin D supplements that droppers accompanying these products should be clearly and accurately marked for 400 international units (1IU is the biological equivalent of 25ng cholecalciferol/ergocalciferol). In addition, for products intended for infants, the FDA recommends the dropper hold no more than 400IU. For infants (birth to 12 months), the tolerable upper limit (maximum amount that can be tolerated without harm) is set at 25μg/day (1,000IU). One thousand micrograms per day in infants has produced toxicity within one month. After being commissioned by the Canadian and American governments, the Institute of Medicine (IOM) , has increased the tolerable upper limit (UL) to 2,500IU per day for ages 1–3 years, 3,000IU per day for ages 4–8 years and 4,000IU per day for ages 9–71+ years (including pregnant or lactating women).
Calcitriol itself is auto-regulated in a negative feedback cycle, and is also affected by parathyroid hormone, fibroblast growth factor 23, cytokines, calcium, and phosphate.
A study published in 2017 assessed the prevalence of high daily intake levels of supplemental vitamin D among adults ages 20+ in the United States, based on publicly available NHANES data from 1999 through 2014. Its data shows the following:
* Over 18% of the population exceeds the NIH daily recommended allowance (RDA) of 600–800 IU, by taking over 1000 IU, which suggests intentional supplement intake.
* Over 3% of the population exceeds the NIH daily tolerable upper intake level (UL) of 4000 IU, above which level the risk of toxic effects increases.
* The percentage of the population taking over 1000 IU/day, as well as the percentage taking over 4000 IU/day, have both increased since 1999, according to trend analysis.