Vitamin D and Health

and hypercalciuria can follow. Hypercalciuria is defined as urinary calcium excretion > 250 mg/d in
women and 275-300 mg/d in men.
7.15 A number of case reports of vitamin D intoxication, following high medicinal doses or excessive use of
food supplements, have been reported in the literature. In these case reports, serum 25(OH)D
concentrations of 300 to more than 1000 nmol/L were associated with intoxication. However, case
reports provide limited information for risk assessment purposes because the doses consumed, where
known, have varied in amount and duration.
7.16 Adverse effects have also been reported in intervention studies examining the effect of vitamin D
supplementation on various health outcomes. These studies provide information on population
groups as well as supplemental doses/serum 25(OH)D concentrations associated with reported
adverse effects. Trials varied in design and few administered vitamin D doses > 100 μg/d (4000 IU). In
most trials where higher daily doses were used, it was rarely for longer than a few months. Only
isolated instances of hypercalcaemia were reported in the intervention studies. Serum calcium
concentrations increased in some trials but remained within the normal range. Only two studies
(Barger-Lux et al., 1998; Heaney et al., 2003) used one or more doses ≥ 100 μg/d (4000 IU/d), in the
absence of calcium supplements, for ≥ 2 months.
7.17 Heaney et al. (2003) investigated the relationship between steady state vitamin D 3 intake and serum
25(OH)D concentration. Vitamin D 3 doses of 0, 25, 125 or 250 μg/d (0, 1000, 5000 or 10,000 IU/d)
were administered to healthy men (n=67) for 20 weeks over the winter in Omaha, US. Mean serum
25(OH)D concentration was 70 nmol/L at baseline, which increased in proportion to the dose. Limited
information was provided on changes in serum calcium concentrations but indicated that none of the
men in the top two dose groups (n=31) had concentrations above the normal reference range after
treatment. The IOM observed that vitamin D intakes of 125 μg/d (5000 IU/d) achieved serum
25(OH)D concentrations of 100-150 nmol/L (but not exceeding 150 nmol/L) after 160 days of
administration.
7.18 Barger-Lux et al. (1998) investigated the relationship between graded oral dosing with vitamin D 3 for 8
weeks and changes in serum 25(OH)D concentration in healthy young men (n=116; mean age, 28y).
Doses of 25, 250 or 1250 μg/d (1000; 10,000; or 50,000 IU/d) resulted in mean increases in serum
25(OH)D concentration of 28.6, 146.1 and 643.0 nmol/L respectively above the mean baseline
concentration (67 nmol/L). No statistically significant changes were detected in mean baseline serum
calcium concentration (2.41 mmol/L).
Kidney stones
7.19 Prolonged hypercalciuria is a risk factor for kidney stones. Although available human studies suggest
that high intakes of vitamin D alone are not associated with an increased risk of kidney stones,
combined supplementation with calcium may increase risk. An RCT of postmenopausal women
(n=36,282; mean age, 62y) (Jackson et al. (2006) reported an increased risk of kidney stones in women
given a daily calcium supplement of 1000 mg plus 10 μg (400 IU) of vitamin D for up to 7 years
compared to those who received placebo (HR=1.17; 95% CI, 1.02-1.34). However, total intakes of
vitamin D in this study were below those associated with hypercalcaemia.
Fall and fractures
7.20 An RCT (Sanders et al., 2010) of women in Australia (n=2256; age ≥ 70y) reported an increased risk of
fracture in the vitamin D 3 supplemented group (single annual dose of 12,500 μg/500,000 IU for 3-5
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