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Efficacy and safety of vitamin D₃ intake exceeding the lowest observed adverse effect level^1,2,3

¹ From the Department of Pathology and Laboratory Medicine, the University of Toronto and Mount Sinai Hospital, Toronto, Canada, and DiaSorin Inc, Stillwater, MN.

Background: The Food and Nutrition Board of the National Academy of Sciences states that 95 µg vitamin D/d is the lowest observed adverse effect level (LOAEL).

Objective: Our objective was to assess the efficacy and safety of prolonged vitamin D₃ intakes of 25 and 100 µg (1000 and 4000 IU)/d. Efficacy was based on the lowest serum 25-hydroxyvitamin D [25(OH)D] concentration achieved by subjects taking vitamin D₃; potential toxicity was monitored by measuring serum calcium concentrations and by calculating urinary calcium-creatinine ratios.

Design: Healthy men and women (n = 61) aged 41 ± 9 y ( ± SD) were randomly assigned to receive either 25 or 100 µg vitamin D₃/d for 2–5 mo, starting between January and February. Serum 25(OH)D was measured by radioimmunoassay.

Results: Baseline serum 25(OH)D was 40.7 ± 15.4 nmol/L ( ± SD). From 3 mo on, serum 25(OH)D plateaued at 68.7 ± 16.9 nmol/L in the 25-µg/d group and at 96.4 ± 14.6 nmol/L in the 100-µg/d group. Summertime serum 25(OH)D concentrations in 25 comparable subjects not taking vitamin D₃ were 46.7 ± 17.8 nmol/L. The minimum and maximum plateau serum 25(OH)D concentrations in subjects taking 25 and 100 µg vitamin D₃/d were 40 and 100 nmol/L and 69 and 125 nmol/L, respectively. Serum calcium and urinary calcium excretion did not change significantly at either dosage during the study.

Conclusions: The 100-µg/d dosage of vitamin D₃ effectively increased 25(OH)D to high-normal concentrations in practically all adults and serum 25(OH)D remained within the physiologic range; therefore, we consider 100 µg vitamin D₃/d to be a safe intake.

Key Words: Cholecalciferol • calcidiol • vitamin D₃ • hypercalciuria • toxicity • lowest observed adverse effect level • LOAEL • efficacy

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