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120 R. Scragg
In summary, the results from these three studies clearly called for a reevaluation of
the hypothesis that vitamin D was a cause of coronary heart disease. Their overall con-
clusion was that vitamin D levels in patients with coronary heart disease were either the
same as, or lower than, in healthy controls. The major limitation of these studies is their
small sample sizes, which is a likely reason for their insufficient statistical power to
observe consistent significant reductions in serum 25OHD levels among heart disease
cases, as reported in subsequent larger epidemiological studies (see below).
6.2.2.3 25-Hydroxyvitamin D and Serum Cholesterol
These three early case–control studies of serum 25OHD and coronary heart disease
also provided important information about the association between vitamin D status
and serum cholesterol. Animal studies in the 1950s and 1960s had shown previ-
ously that the combination of high dietary intake of vitamin D and cholesterol could
produce raised blood cholesterol levels and atherosclerotic lesions [38, 39]. An
experimental study in humans found that daily vitamin D doses of 50,000 or
1,000 IU for 21 days significantly increased serum cholesterol levels, although the
study can be criticized because of the lack of a control group [40]. Analyses of
baseline cross-sectional data from the Tromso Heart Study reported a significant
positive association (p = 0.0013) between dietary vitamin D intake and serum
cholesterol in men aged 20–50 years [41].
However, after the advent of assays for 25OHD, the Danish and Norwegian stud-
ies found no association between serum 25OHD and serum cholesterol [36, 37].
This result has been confirmed by subsequent epidemiological studies [42–45].
Thus, the overall evidence to date suggests that any association between vitamin D
and CV disease does not involve serum cholesterol.
6.3 1980s to 1990s: Vitamin D May Protect Against
Cardiovascular Disease
6.3.1 Hypothesis
The early studies showing that more than 80% of vitamin D comes from sun
exposure [33, 34] emphasized the importance of solar ultraviolet (UV) radiation
in determining vitamin D status, and provided a possible link between vitamin
D and some of the descriptive epidemiological variations in CV disease rates.
UV-B irradiation (wavelengths 280–320 nm), acting on the skin, converts the precursor
7-dehydrocholesterol into vitamin D , which comprises most of the vitamin D in
3
humans [46]. The intensity of UV radiation on the surface of the earth varies
with season being highest in summer and lowest in winter, decreases with
increasing latitude from the equator, and increases with altitude by up to 18%
per 1,000 m [47].