High dose vitamin d side effects
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High-Dose Vitamin D Side Effects: A Comprehensive Review
Introduction to High-Dose Vitamin D Supplementation
High-dose vitamin D supplementation has gained popularity due to its potential health benefits. However, concerns about its safety, particularly regarding calcium metabolism, have prompted numerous studies to investigate possible adverse effects.
Hypercalcemia and Hypercalciuria
Increased Risk of Hypercalcemia
Several studies have reported an increased risk of hypercalcemia with high-dose vitamin D supplementation. A systematic review and meta-analysis found that long-term vitamin D supplementation significantly increased the risk of hypercalcemia (RR: 1.54; 95% CI: 1.09, 2.18). Another study observed a trend towards increased hypercalcemia in participants receiving high doses of vitamin D for one year or more. Additionally, a randomized controlled trial (RCT) reported mild hypercalcemia in 9% of participants taking 10,000 IU/day of vitamin D, compared to 3% in those taking 4,000 IU/day.
Hypercalciuria Incidence
Hypercalciuria, or elevated calcium levels in urine, is another concern. The same meta-analysis indicated an increased risk of hypercalciuria with vitamin D supplementation (RR: 1.64; 95% CI: 1.06, 2.53). In the Calgary Vitamin D Study, hypercalciuria was more common in participants taking higher doses of vitamin D (31% in the 10,000 IU/day group). However, some studies found the effect on hypercalciuria to be inconclusive.
Kidney Stones
No Significant Increase in Kidney Stone Risk
Despite concerns, most studies have not found a significant increase in kidney stone risk with high-dose vitamin D supplementation. A systematic review and meta-analysis reported no significant difference in kidney stone incidence between vitamin D and placebo groups (RR: 0.66; 95% CI: 0.41, 1.09). Similarly, the ViDA study, which involved monthly doses of 100,000 IU vitamin D3, found no significant difference in kidney stone events between the vitamin D and placebo groups.
General Adverse Events
Comparable Adverse Event Rates
Overall, high-dose vitamin D supplementation does not appear to significantly increase the rate of general adverse events. In a large RCT, the incidence of adverse events was similar between the vitamin D and placebo groups, with a hazard ratio (HR) of 1.03 (95% CI: 0.90, 1.18). Another study found no significant increase in total adverse events or kidney stones with long-term high-dose vitamin D supplementation.
Special Populations
Critically Ill Patients
In critically ill patients, a single ultra-high dose of vitamin D3 (540,000 IU) was found to correct vitamin D deficiency without causing hypercalcemia or hypercalciuria. This suggests that high-dose vitamin D can be safely administered in acute settings under medical supervision.
Children
High-dose vitamin D supplementation in children aged 0 to 6 years was not associated with an increased risk of serious adverse events, indicating that it is well-tolerated in this age group.
Conclusion
While high-dose vitamin D supplementation can increase the risk of hypercalcemia and hypercalciuria, it does not significantly raise the risk of kidney stones or general adverse events. These findings suggest that high-dose vitamin D can be safe for most populations when monitored appropriately. However, caution is advised, and further research is needed to confirm these findings and establish optimal dosing regimens.
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