The most worrisome potential adverse effects of excessive vitamin D are hypercalcemia, bone demineralization, nephrocalcinosis, and cardiac arrhythmias. However, these conditions don't really arise until serum levels get above 150 ng/mL, Dr. Crew said, a level that would require high amounts of vitamin D supplementation over a long period.
A study done in 2004 looked at daily doses of 10,000 IU for up to 5 months, and found no evidence of toxicity (J. Steroid Biochem. Mol. Biol. 2004;89-90:575-9).
Researchers at Columbia are in the midst of a trial assessing the effect of cholecalciferol (vitamin D3) at 20,000 IU and 30,000 IU/week, in vitamin D–deficient pre- and postmenopausal women at high risk of breast cancer. The women will be treated for a full year. The study will ultimately involve 80 participants, and investigators are tracking a number of breast-specific outcomes including tissue changes on biopsy, changes in breast fibrodensity, and cancer markers in urine and serum.
The weekly doses in this study translate to roughly 2,800 IU and 4,300 IU/day, which are quite a bit higher than the IOM's new recommendation. In an interview, Dr. Crew said the doses do fall close to the IOM's new safe upper limits, but her group has no plan to change the protocol in light of the IOM report.
“For new participants that we're screening, there has been some hesitation from a few women, but others are still willing to participate,” she noted.
According to Julie Campbell, a research fellow involved in the study, 20 premenopausal and 14 postmenopausal women have completed the yearlong intervention, with no evidence of any adverse effects at either dose level. “There have been no cases of hypercalcemia so far, and only one woman has shown high urine calcium levels,” she said.
The high-dose supplementation did produce fairly rapid increases in serum levels. Among the premenopausal women, mean levels had reached the 50- to 60-ng/mL range within 3 months. The 30,000-IU/week doses resulted in a larger increase than did the 20,000-IU/week doses. But even at these high doses, none of the subjects so far have shown potentially toxic serum levels in the range of 150 ng/mL and higher.
Many of the correlations found between vitamin D level and breast cancer risk have also been observed in studies of colorectal cancer, said Dr. Roberd M. Bostick, professor of epidemiology at Emory University, Atlanta.
A dose-response trial is underway involving 272 patients with sporadic colorectal adenoma. The four-arm, placebo-controlled study will assess tissue changes and biomarkers after 6 months of vitamin D supplementation at 1,000, 2,000, and 4,000 IU/day, Dr. Bostick said at the meeting.
Although the IOM report cites the potential dangers of high-dose vitamin D, it is important to realize that “they still raised the RDA from 400 to 600 IU daily and the upper safety limit was doubled from 2,000 IU to 4,000 IU daily. This is still progress in terms of being able to raise people's serum 25-hydroxyvitamin D to sufficient levels,” Dr. Crew said in an interview.
The researchers did not report any financial conflicts.