Page 145 - Vitamin D and Cancer

132 R. Scragg

2008 of results from three cohort studies showing that blood levels of 25OHD
predict risk of CV disease and total mortality in the general population (see
Sect. 6.4.2). These findings are strengthened further by a meta-analysis showing
that vitamin D reduces total mortality [157] and results from cohort studies of
dialysis patients showing that active vitamin D reduces total mortality and CV
disease (see Sect. 6.4.1). This rush of publications stands in stark contrast with
the dearth of large-scale epidemiological studies published during the previous
half-century.
When this recent evidence is looked at in its totality, it meets many of the criteria
for causation proposed originally for epidemiological studies by Bradford-Hill
[200]. These include the temporality requirement of evidence from cohort studies
that exposure (low vitamin D status) precedes the onset of the disease, evidence of
reversibility from clinical trials that vitamin D supplementation reduces total mor-
tality (most probably through preventing CV disease), consistency of evidence as
shown by the agreement in the findings from cohorts studies in the general popula-
tion and dialysis patients, and evidence of a moderately strong association with a
doubling in the risk of CV disease between highest and lowest quantiles of 25OHD.
Lastly, evidence of biological plausibility has come from recent animal and clinical
studies identifying a number of mechanisms to explain the possible link between
vitamin D and CV disease. These include effects of vitamin D on immune and
inflammatory processes, endothelial function, the rennin–angiotensin system,
MMPs and insulin resistance.
The evidence from recent cohort studies is now so compelling that large-scale
clinical trials are required to determine, once and for all, whether vitamin D
supplementation prevents CV disease, both in the general population and in patient
populations [133–135, 137, 157]. As the great British epidemiologist Sir Richard
Doll, who changed his view from opposing to supporting the beneficial effects of
vitamin D and sun exposure before he died, said “This isn’t difficult science. We
should have answers” [201]. Neither is it expensive science since vitamin D is very
cheap compared with most other treatments for CV disease. If clinical trials were
to confirm that vitamin D prevents CV disease, the potential benefits would be
substantial.

References

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2. Friedman WF (1967) Vitamin D as a cause of the supravalvular aortic stenosis syndrome.
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3. Taussig HB (1966) Possible injury to the cardiovascular system from vitamin D. Ann Intern
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4. Stare FJ et al (1966) Congenital supravalvular aortic stenosis, idiopathic hypercalcemia, and
vitamin D. Nutr Rev 24:311–313
5. Seelig MS (1969) Vitamin D and cardiovascular, renal, and brain damage in infancy and
childhood. Ann N Y Acad Sci 147:539–582