Comprehensive Safety Monitoring of 12-Month Daily 7000-IU Vitamin D 3 Supplementation in Human Immunodeficiency Virus–Infected Children and Young Adults

Abstract

Background: There is uncertainty whether long-term daily dosing with vitamin D₃ (cholecalciferol) supplementation (vitD₃) above the 4000-IU/d dietary reference intake upper tolerable limit in children and adults is safe. As part of a randomized placebo-controlled trial, we determined if supplementation with 7000-IU/d vitD₃ for 12 months in human immunodeficiency virus (HIV)–Infected subjects was safe and/or associated with metabolic outcomes. Material and Methods: A total of 58 HIV-infected subjects—aged 9–24.9 years and stratified by mode of HIV acquisition (perinatal or behavioral)—were recruited, randomized to 7000-IU/d vitD₃ or placebo, and followed at 3, 6, and 12 months with physical examinations, blood and urine sampling for measures of 25(OH)D (serum 25-hydroxyvitamin D), metabolic status, safety measures, and HIV immune status. Safety was defined by a low incidence (<5%) of the study-defined serious adverse events—that is, elevated serum calcium plus 25(OH)D >160 ng/mL—and no changes in hematologic, liver, renal, metabolic, lipid, or inflammatory status. Results: Randomization groups did not differ in demographic characteristics, vitamin D status, or HIV disease status at baseline. Over the 12 months, serum 25(OH)D increased with supplementation. No subject experienced a serious adverse safety event; none had 25(OH)D >80 ng/mL at any time. There were no clinically significant changes in hematologic, liver, renal, metabolic, lipid, or inflammatory status. Conclusions: Safety of daily 7000-IU vitD₃ supplementation in children and young adults with HIV was comprehensively monitored over 12 months. High-dose daily vitD₃ supplementation was efficacious in improving vitamin D status, and there were no safety events.