Randomized comparison of the effects of the vitamin D3 adequate intake versus 100 mcg (4000 IU) per day on biochemical responses and the wellbeing of patients

Abstract

Background: For adults, vitamin D intake of 100 mcg (4000 IU)/day is physiologic and safe. The adequate intake (AI) for older adults is 15 mcg (600 IU)/day, but there has been no report focusing on use of this dose.

Methods: We compared effects of these doses on biochemical responses and sense of wellbeing in a blinded, randomized trial. In Study 1, 64 outpatients (recruited if summer 2001 25(OH)D <61 nmol/L) were given 15 or 100 mcg/day vitamin D in December 2001. Biochemical responses were followed at subsequent visits that were part of clinical care; 37 patients completed a wellbeing questionnaire in December 2001 and February 2002. Subjects for Study 2 were recruited if their 25(OH)D was <51 nmol/L in summer 2001. 66 outpatients were given vitamin D; 51 completed a wellbeing questionnaire in both December 2002 and February 2003.

Results: In Study 1, basal summer 25-hydroxyvitamin D [25(OH)D] averaged 48 +/- 9 (SD) nmol/L. Supplementation for more than 6 months produced mean 25(OH)D levels of 79 +/- 30 nmol/L for the 15 mcg/day group, and 112 +/- 41 nmol/L for the 100 mcg/day group. Both doses lowered plasma parathyroid hormone with no effect on plasma calcium. Between December and February, wellbeing score improved more for the 100-mcg/day group than for the lower-dosed group (1-tail Mann-Whitney p = 0.036). In Study 2, 25(OH)D averaged 39 +/- 9 nmol/L, and winter wellbeing scores improved with both doses of vitamin D (two-tail p < 0.001).

Conclusion: The highest AI for vitamin D brought summertime 25(OH)D to >40 nmol/L, lowered PTH, and its use was associated with improved wellbeing. The 100 mcg/day dose produced greater responses. Since it was ethically necessary to provide a meaningful dose of vitamin D to these insufficient patients, we cannot rule out a placebo wellbeing response, particularly for those on the lower dose. This work confirms the safety and efficacy of both 15 and 100 mcg/day vitamin D3 in patients who needed additional vitamin D.

Figure 1

Flowchart showing numbers of patients during the duration of these studies.

Figure 2

Biochemical responses to vitamin D₃ supplementation of endocrine outpatients during one year. Open bars indicate pre-supplementation data; boxes with intermediate shading indicate data at 2–6 months; darkest boxes, indicate data after >6 months of vitamin D. By the second visit after starting vitamin D, plasma 25(OH)D was higher in those taking 100 mcg/day than in those taking 15 mcg/day (values marked b differ significantly from the group's baseline values marked a, p < 0.001, by paired t-test). 25(OH)D values marked b differ significantly from each other, conventional Students t-test, p = 0.006). PTH values marked c differ significantly from the group's baseline value, p = 0.003; PTH values marked d differ significantly from the group's baseline value, p = 0.013.

Figure 3

Cross-sectional presentation of the effect of duration of vitamin D supplementation on quartiles of well-being scores obtained during winter 2002–2003. The boxes with solid perimeters indicate new, Study-2 patients; the boxes with dashed-line perimeter indicate patients who had been consuming their vitamin D since December the previous year (from Study 1). Shaded boxes indicate the data for February, 2002. Spearman's non-parametric correlation of well-being vs months was significant and negative with the higher dose (p = 0.002), but the correlation was not significant for the lower dose (p = 0.108). Statistical comparisons among these data are presented in Table 2.