Page 142 - Vitamin D and Cancer

6 Vitamin D: Cardiovascular Function and Disease 129

been further reduced by poor compliance as only 59% of participants took ³ 80% of
the study medication. Lastly, the control group was able to continue taking vitamin
D supplements, resulting in contamination.
Further evidence from randomized trials suggesting a beneficial effect of
vitamin D against CV disease comes from a recent meta-analysis of vitamin D
supplementation and all-cause mortality [157]. The results of this meta-analysis are
relevant since CV disease is the main cause of mortality in developed countries. It
summarized 18 randomized clinical trials published from 1992 to 2006, which
included data from the Women’s Health Initiative trial [158], 15 studies in Europe,
and two studies from Australia and New Zealand. The meta-analysis found that
vitamin D supplementation produces a 7% relative reduction in all-cause mortality
[157]. Most of the prevented deaths in the treated group are likely to have been
from CV and infectious diseases, since the weighted mean follow-up period was
5.7 years, too short to detect any benefit in preventing cancer deaths [159]. These
findings are consistent with the cohort studies of dialysis patients (described above)
which have reported lower all-cause mortality in patients prescribed active vitamin
D [122, 124–129, 131, 132].
A 7% relative reduction in all-cause mortality may seem small. However, the
weighted vitamin D dose of 528 IU/day for all studies combined is likely to have
only increased blood 25OHD levels by 10–15 nmol/L [155]. As mentioned above,
this daily vitamin D dose is much lower than that currently recommended to main-
tain serum 25OHD at optimum levels [156]. Thus, the potential beneficial effect of
vitamin D supplementation on all-cause mortality may be higher than 7% if larger
vitamin D doses (>2,000 IU/day) are given which increase blood 25OHD levels up
to 100 nmol/L [160].

6.4.4 Cardiovascular Pathophysiology

Since the start of the millennium, numerous publications from research on animal
models and from patients with CV disease have greatly increased understanding of
the mechanisms involved in the possible protective effect of vitamin D against CV
disease. These mechanisms, reviewed below, involve beneficial changes in inflam-
matory processes, endothelial function, matrix metalloproteinases (MMPs), and the
renin–angiotensin system (Fig. 6.2).

6.4.4.1 Inflammatory Factors

Until the 1990s, the dominant view held that the major risk factors of CV disease
were cigarette smoking, hypercholesterolemia, and hypertension (the latter two
caused by dietary saturated fats and physical inactivity), which exerted their effects
over many years of exposure [161]. There was no place in this chronic disease
model for inflammation, despite evidence from many countries showing winter