Vitamin D and Health

heterogeneity among trials for dose of vitamin D and achieved serum 25(OH)D concentration. Vitamin
D doses of 17.5-25 µg/d (700-1000 IU/d) reduced fall risk (pooled RR=0.81, 95% CI, 0.71-0.92) but
doses of 5-10 µg/d (200-400 IU/d) did not (pooled RR=1.10; 95% CI, 0.89-1.35). Fall risk was also
reduced with achieved serum 25(OH)D concentrations ≥ 60 nmol/L (pooled RR=0.77; 95% CI, 0.65-
0.90) but not with concentrations < 60 nmol/L (pooled RR=1.35; 95% CI, 0.98-1.84). Active forms of
vitamin D reduced fall risk by 22% (pooled RR=0.78; 95% CI, 0.64-0.94).
6.138 The IOM report highlighted a number of limitations in these meta-analyses which may have influenced
the overall results, including omission of some studies that met the inclusion/exclusion criteria and
inclusion of one study that did not meet the inclusion criteria. Another criticism related to the
inappropriate presentation and interpretation of the meta-regression analysis of the relative risk
against vitamin D dose or achieved serum 25(OH)D concentration. A reanalysis by the IOM reported a
null effect of vitamin D supplementation on falls.
Evidence considered since IOM report (Tables 28-30, Annex 2)
Systematic reviews and meta-analyses
6.139 A Cochrane review (Cameron et al., 2012) which assessed the effect of vitamin D supplementation on
fall prevention in adults aged > 65y 51 in nursing care facilities and hospitals reported a significant
reduction in rate of falls (rate ratio=0.63, 95% CI, 0.46-0.86; 5 trials; n=4603) but not risk of falling
(RR=0.98, 95% CI 0.89 to 1.09; 6 trials 52 ; n=5186). Mean baseline serum 25(OH)D concentration in the
included studies ranged from 23 to 59 nmol/L.
6.140 A second Cochrane review investigated the effect of vitamin D supplementation on fall prevention in
community dwelling adults aged ≥ 60y 53 (Gillespie et al., 2012). Overall, vitamin D did not reduce rate
of falls (RaR 54 =1.00; 95% CI, 0.90-1.11; 7 trials; n=9324) or risk of falling (RR=0.96; 95% CI, 0.89-1.03;
13 trials; n=26,747). A post hoc subgroup analysis of 4 trials that specifically recruited participants
with ‘low’ baseline serum 25(OH)D concentration 55 reported a greater reduction in rate of falls
(RaR=0.57; 95% CI, 0.37-0.89; 2 trials 56 ; n=260; baseline serum 25(OH)D concentration, 24-28 nmol/L)
and risk of falling (RR=0.70; 95% CI, 0.56-0.87; 4 trials 57 ; n=804; baseline serum 25(OH)D
concentration, 24-55 nmol/L). For trials that did not select on baseline serum 25(OH)D concentration,
vitamin D supplementation had no effect on rate of falls (RaR=1.02; 95% CI, 0.88-1.19; 3 trials;
n=3669) or risk of falling (RR=1.00; 95% CI, 0.93-1.07; 9 trials; n=25,943).
6.141 A meta-analysis (Kalyani et al., 2010) of 10 RCTs in community dwelling and institutionalised adults
≥ 60y (n=2,932) reported a significant reduction in falls with supplementation (RR=0.86; 95% CI, 0.79-
0.93), with fewer falls in the following subgroups: those aged < 80y; when calcium was coadministered,
when vitamin D 3 was used at doses > 20 µg/d (800 IU/d), supplementation > 6 months
and there was no previous history of falls or fractures. Mean baseline serum 25(OH)D concentrations
in the included studies ranged from 23 to 82 nmol/L. Meta-regression analysis showed no significant
linear association between vitamin D dose or duration and risk of falls.
51 Trials were also included if the mean age was > 65y.
52 1 trial tested a vitamin D supplement that included vitamin D plus calcium (Grieger, 2009).
53 Trials also included if mean age minus 1 standard deviation was more than 60 years.
54 Rate ratio.
55 Baseline serum 25(OH)D in the 4 trials with lower concentrations: range 23.7-28 nmol/L (Dhesi et al, 2004), mean (SD) 25.2±12.9 nmol/L (Pfeifer et
al, 2000), mean (SD) 54.5±18 nmol/L (Pfeifer et al, 2009); mean (SD) 44.8±12.7 nmol/L (Prince et al, 2008).
56 Dhesi et al (2004); Pfeifer et al (2000).
57 Dhesi et al (2004); Pfeifer et al (2000); Pfeifer et al (2009); Prince et al (2008).
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