Page 131 - Vitamin D and Cancer

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of animal models of arteriosclerosis caused by hypervitaminosis D, using mega-doses
of 5,000–10,000 IU/kg/day [17, 18], equivalent to daily doses of 350,000–700,000 IU
for a 70 kg adult human; and case reports of arterial calcification and hypertension
in patients taking up to 170,000 IU of vitamin D/day [19–21]. Despite dissenting
opinion [22] and isolated reports that vitamin D could prevent myocardial calcifica-
tion in rats [23] and assist with the treatment of vascular calcification, heart failure,
and cardiac arrthymias in humans [24–27], reviews in the 1970s were convinced
about the causal role of vitamin D in atherosclerosis and coronary heart disease [15,
16, 28]. The authors of one of these reviews, although writing nearly 4 decades ago,
could be addressing contemporary concerns by stating:
The tragic “operation over-kill” of adding vitamin D to almost everything excepting cigars
may well be one of the most important pathogenic factors in human atherosclerosis. People
in the USA may well be the victims of Madison Avenue advertising tycoons, food
manufacturers, unsuspecting dietitians, and indifferent physicians who have probably all
played a role in adding excessive amounts of vitamin D to many foods [15].
Looking back at these reports raises an obvious question: Why were their opinions so
different to the results from recent cohort studies (see Sect. 6.4.2.1) which have con-
sistently reported inverse associations between vitamin D status and risk of CV dis-
ease? Two points can be made about the approach to research in the 1960s and 1970s.
Firstly, there was an overreliance on case reports in determining causation. These case
reports were limited because they often had very small numbers of selected patients,
who may not have been representative of all patients with a particular condition, and
did not include a control group to help decide whether cases had a higher-than-
expected intake of vitamin D. Secondly, there was a lack of appreciation that the
doses of vitamin D given in the animal models of arteriosclerosis were orders of
magnitude higher than those normally ingested by the general human population.
A recent review of the evidence on vitamin D and vascular calcification has con-
cluded that vitamin D exerts a biphasic effect on vascular calcification with adverse
effects occurring when body vitamin D levels are very low or very high [29].

6.2.2 Early Epidemiological Studies

6.2.2.1 Dietary Vitamin D and Cardiovascular Disease

Epidemiological studies carried out in the 1970s were influenced by the prevailing
opinion of the time that vitamin D was a cause of CV disease. Positive correlations
between vitamin D intake measured in national surveys and standardized mortality
ratios for ischemic heart disease (r = 0.58) and cerebrovascular disease (r = 0.49)
during 1964–1969 were reported in an ecological study of eight regions within
England and Wales [30]. A population-based myocardial infarction case–control
study in Tromso (Norway) reported significantly higher mean daily intake of
vitamin D in cases (males 31.28 mg, females 34.05 mg) compared to age- and
sex-matched controls (males 22.68 mg, females 20.68 mg) [31]. The limitations of