Vitamin D and Health

that this is because vitamin D is metabolised to 25(OH)D in the liver at the same time as the dietary
triglycerides are being repackaged as very low density lipoprotein (VLDL) particles which are secreted
back into the circulation with some 25(OH)D incorporated into the VLDL; since endothelial cells have
specific receptors for lipoproteins, the uptake of LDL could deliver 25(OH)D to these cells.
6.219 Ecological studies have reported increased CVD mortality and hypertension at more Northern
latitudes and during the winter (Grimes et al., 1996; Rostand, 1997; Zittermann et al., 2005). There is
evidence suggesting that inflammatory processes are involved in the development of CVD (Van Lente,
2000) and the potential role of vitamin D in modulating inflammation has been proposed as a possible
mechanism providing linkage to CVD. PTH concentration is inversely correlated with serum 25(OH)D
concentration and epidemiological studies have demonstrated an association between elevated and
high-normal PTH concentration and increased risk of cardiovascular events and mortality (Pilz et al.,
2010; van Ballegooijen et al., 2013). PTH suppression, by vitamin D supplementation, might therefore
reduce CVD risk.
6.220 Since vitamin D has the potential to increase calcium absorption in the presence of high calcium
intakes, it is also biologically plausible that vitamin D might increase vascular calcification and as a
consequence, increase CVD risk.
6.221 IOM Report: The IOM report was unable to identify any RCTs that examined CVD as a pre-specified
primary outcome. Several trials analysed CVD as a secondary outcome but did not find a reduction in
CVD risk with vitamin D supplementation. Observational studies supported a relationship between
serum 25(OH)D concentration and presence of CVD but not risk for developing CVD. The IOM
concluded that it could not draw an inference about the efficacy of this indicator to support DRI
development.
Evidence considered since the IOM report (Tables 40-41, Annex 2)
CVD
Systematic reviews and meta-analyses
6.222 RCT data on vitamin D supplementation and CVD are derived mainly from studies designed to evaluate
effects of vitamin D supplementation on musculoskeletal outcomes and need, therefore, to be
interpreted with caution.
6.223 A systematic review of 8 randomised trials with CVD as a secondary outcome (Wang et al., 2010a)
reported no significant associations for CVD with vitamin D supplementation (supplemental daily
doses of approximately 25 µg/1000 IU; pooled RR=0.90; 95% CI, 0.77–1.05), calcium supplementation
or a combination of vitamin D plus calcium supplementation.
6.224 In contrast, a meta-analysis of 3 randomised placebo controlled trials (Bolland et al., 2011) reported
that calcium and vitamin D increased the risk of myocardial infarction (MI) (RR=1.21; 95% CI, 1.01-
1.44; p=0.04), stroke (RR=1.20; 95% CI, 1.00-1.43; p=0.05) and the composite of MI or stroke (RR=1.16;
95% CI, 1.02-1.32; p=0.02).
6.225 Another systematic review (Ford et al., 2014) of 21 RCTs (n=13,033; mean/median age ≥ 60y; ≥ 1 year
follow-up) reported that estimated HRs (95% CIs) for vitamin D compared with placebo or control for
cardiac failure, MI and stroke were not significant: 0.82 (0.58-1.15), 0.96 (0.83-1.10) and 1.07 (0.91-
1.29) respectively.
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