Iron is the second most abundant metal in the Earth’s crust. Despite being present in trace amounts, it is an essential trace element for the human body, although it can also be toxic due to oxidative stress generation by the Fenton reaction, causing organic biomolecule oxidation. This process is the basis of numerous pathologies, including cardiovascular diseases (CVD). The relationship between iron and cardiovascular disease was proposed in 1981 by Jerome Sullivan. Since then, numerous epidemiological studies have been conducted to test this hypothesis. The aim of this review is to present the main findings of the chief epidemiological studies published during the last 32 years, since Sullivan formulated his iron hypothesis, suggesting that this element might act as a risk factor for cardiovascular disease. We have analyzed 55 studies, of which 27 supported the iron hypothesis, 20 found no evidence to support it and eight were contrary to the iron hypothesis. Our results suggest that there is not a high level of evidence which supports the hypothesis that the iron may be associated with CVD. Despite the large number of studies published to date, the role of iron in cardiovascular disease still generates a fair amount of debate, due to a marked disparity in results.
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