Page 135 - Vitamin D and Cancer

122 R. Scragg

when given in physiological doses. This was stimulated by the identification of a
receptor to 1,25-dihydroxyvitamin D (1,25(OH) D), firstly in cultured rat heart
2
identified in 1983 [70, 71], and subsequently confirmed by others [72], which was
found to be located in the nucleus [73]. Together with the additional finding of a
vitamin-D-dependent calcium-binding protein in myocardial tissue in 1982 [74],
these studies supported a role for 1,25(OH) D in regulating CV function.
2
Further studies were carried out with the aim of elucidating the possible CV
mechanisms involved with vitamin D. When rats reared deficient in vitamin D were
compared to those given 30 IU of vitamin D /day (equivalent to about 8,500 IU/day
3
for 70 kg human adult), the vitamin-D-deficient rats had increased cardiac contrac-
tion [75], and myocardial hypertrophy due to myocardial collagen deposition and
myocyte hyperplasia and hypertrophy [76–79]. These effects were independent of
changes in serum calcium, suggesting a direct effect of vitamin D, since myocardial
accumulation of calcium after very high vitamin D doses could be blocked by
calcium channel blockers [80, 81]; and in contrast with the earlier studies showing
adverse effects from excessive vitamin D which were secondary to increases in
serum calcium (Sect. 6.2.1). However, the health implications of these studies were
unclear as the increased cardiac contractility in vitamin D deficiency could be
interpreted as beneficial, while the myocardial hypertrophy could be detrimental.
Evidence was also accumulating of a role for vitamin D in regulating blood
pressure. A receptor to 1,25(OH) D was described in smooth muscle tissue [82],
2
and also in endothelial cells with early evidence of autocrine synthesis of
1,25(OH) D that was a function of 25OHD substrate concentration [83]. Alterations
2
in vitamin D metabolism were observed in spontaneously hypertensive rats which
were shown to have decreased plasma levels of 1,25(OH) D [84]; while injection
2
of the same metabolite in normotensive rats resulted in a delayed increase in blood
pressure consistent with a genomic mechanism [85].

6.3.3 Human Studies

6.3.3.1 Blood Pressure

A key stimulus for research on vitamin D and hypertension were the studies in the
early 1980s showing elevated parathyroid hormone (PTH) levels in hypertension
cases [86, 87], which was speculated as being a possible response to increased
urinary calcium loss, along with research showing inverse associations between
blood levels of both 1,25(OH) D and PTH with renin in hypertension patients [88].
2
Given the well-documented inverse association between PTH and vitamin D status,
these studies suggested that low vitamin D levels might be a risk factor for hyper-
tension. A US cross-sectional study reported an inverse association between dietary
vitamin and systolic blood pressure [89]. However, results from studies of the asso-
ciation between blood levels of 25OHD and blood pressure were inconclusive. An
early Polish study found that plasma levels of 25OHD were lower in hypertension