Efficacy and safety of vitamin D3 intake exceeding the lowest observed adverse effect level.
BACKGROUND
The Food and Nutrition Board of the National Academy of Sciences states that 95 microg 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 microg (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.


METHODS
Healthy men and women (n = 61) aged 41 +/- 9 y (mean +/- SD) were randomly assigned to receive either 25 or 100 microg 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 (mean +/- SD). From 3 mo on, serum 25(OH)D plateaued at 68.7 +/- 16.9 nmol/L in the 25-microg/d group and at 96.4 +/- 14.6 nmol/L in the 100-microg/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 microg 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-microg/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 microg vitamin D3/d to be a safe intake.
Vieth
R
R
Mount Sinai Hospital, Toronto, Ontario, Canada. rvieth@mtsinai.on.ca
Chan
P C
PC
MacFarlane
G D
GD
D000328:Adult; D000704:Analysis of Variance; D001835:Body Weight; D002112:Calcifediol / Q000097:blood*; D002118:Calcium / Q000032:analysis* / Q000097:blood / Q000652:urine; D002762:Cholecalciferol / Q000008:administration & dosage* / Q000009:adverse effects*; D003404:Creatinine / Q000652:urine; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019055:No-Observed-Adverse-Effect Level; D011863:Radioimmunoassay; D012449:Safety; D013997:Time Factors; D016896:Treatment Outcome
D002762:Cholecalciferol; D003404:Creatinine; D002112:Calcifediol; D002118:Calcium