Vitamin D and Health

Summary - CVD and hypertension
6.237 Intervention studies have generally considered CVD risk as a secondary outcome; these studies, therefore, need
to be interpreted with caution.
6.238 Out of 3 systematic reviews assessing the effect of vitamin D supplementation on CVD outcomes, 2 reported no
significant effect and 1 reported an increased CVD risk with vitamin D plus calcium.
6.239 Prospective cohort studies, overall, report inverse associations between serum 25(OH)D concentration and CVD
risk. Increased risk in these studies was reported at serum 25(OH)D concentrations ranging between
< 25 nmol/L and 60 nmol/L.
6.240 Meta-analyses of intervention studies on vitamin D supplementation and hypertension are inconsistent. A large
systematic review and meta-analysis (46 trials) of placebo-controlled RCTs reported no effect of vitamin D
supplementation on systolic or diastolic blood pressure.
6.241 Observational studies (cohort and cross-sectional) report an inverse association between serum 25(OH)D
concentration and hypertension.
All-cause mortality
6.242 An effect of vitamin D on mortality risk has been observed in numerous observational studies that
have reported associations between low serum 25(OH)D concentration and increased risk of several
chronic diseases (including CVD and cancer).
6.243 IOM Report: The IOM only considered all-cause mortality in the context of adverse effects of excess
vitamin D. It concluded that the data were suggestive of a U-shaped relationship between serum
25(OH)D concentration and all-cause mortality with an increase in risk at concentrations < 30 and
> 75 nmol/L.
Evidence since IOM report (Tables 44-45, Annex 2)
Systematic reviews and meta-analyses
6.244 A Cochrane systematic review and meta-analysis (Bjelakovic et al., 2014) included 56 randomised trials
of any form of vitamin D (n=95,286; mean treatment duration, 4.4 years); 34 trials used vitamin D in
combination with calcium in the intervention group. Participants in most of the trials were women
aged over 70y (a population at greater risk of mortality) and many of the trials were small, with less
than 10 deaths. Overall, treatment with any type of vitamin D decreased mortality (RR=0.97; 95% CI,
0.94-0.99; p=0.02). In analyses of vitamin D given without calcium, vitamin D 3 vs placebo or no
intervention (13 trials; n=12,609) had no statistically significant effect on mortality (RR=0.92; 95% CI,
0.85-1.00; p=0.06); vitamin D 2 administered alone (8 trials; n=17,079) also had no statistically
significant effect on mortality (RR=1.03; 95% CI, 0.96-1.12).
6.245 A meta-analysis of observational prospective studies (Schottker et al., 2014) which combined
individual participant data from 8 cohorts in the USA and Europe (n=26,018; age, 50-79y) estimated a
pooled hazard ratio of 0.64 (95% CI, 0.55-0.74) for the highest versus the lowest fifth of serum
25(OH)D concentration. Cut-offs for serum 25(OH)D quintile concentrations varied by cohort ranging
from < 16 to < 42 nmol/L in the lowest quintile and from ≥ 44 to ≥ 86 nmol/L in the highest.
6.246 Another meta-analysis of observational cohort studies (Chowdhury et al., 2014) summarised results
from 27 cohorts (n=780,990). The pooled hazard ratio was 0.74 (95% CI, 0.67-0.82) for the highest
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