Iron is an essential trace mineral best known for its role as a component of the haemoglobin and myoglobin molecules. In addition, iron is also required as a cofactor in a number of enzymes including the tyrosine and tryptophan hydroxylase enzymes that catalyse the formation of important neurotransmitters. The role of iron in the development of cardiovascular disease has been controversial since it was first postulated that excessive intakes of iron may be detrimental to the health. Iron is usually maintained in a reduced state and tightly bound to proteins but excessive iron stores may have a pro-oxidant effect that lead to tissue inflammation and disease. The iron overload theory suggests that large pools of iron in tissues increase the generation of hydroxyl radicals which subsequently increase oxidative stress. In particular hydroxyl radicals may oxidise low density lipoproteins (LDL) or cause endothelial dysfunction through a reduction in the synthesis of nitric oxide synthase.
The controversial observations regarding iron and cardiovascular disease may be explained by certain methodological differences in studies. To address the controversy a recent meta-analysis analysed the previous studies that had investigated the effects of dietary iron and iron stores on the risk of cardiovascular disease1. Using data from 21 observational studies that included nearly 300,000 participants the authors analysed the data regarding the relative risk of cardiovascular disease and mortality and related this to the iron status of the individuals. The results showed that haem iron intake was associated with an increased risk of cardiovascular disease. However, total iron intake and serum iron concentrations were inversely associated with cardiovascular disease. These nuances in the associations between iron (type of iron and its tissue compartment) and cardiovascular disease may therefore explain the inconsistent findings in the nutritional literature to date.
The association between haem iron and cardiovascular disease may reflect the high red meat content in the typical Western diet. While the meat itself may or may not have negative effects on health, it could be a marker for a low quality diet, and low quality Western diets are associated with an increased risk of cardiovascular disease. Total iron intakes however, were inversely associated with cardiovascular disease which sounds paradoxical. However, plant iron for example from legumes is poorly absorbed and so it is possible to have high intakes of iron but much of this may not be bioavailable. The lack of association between non-haem iron intake and cardiovascular risk in the study can be explained by the inclusion of only two studies in the analysis. The inverse association between serum iron and cardiovascular disease may be explained by large diurnal variations in serum iron stores, suggesting they may not be accurate biomarkers of total stores.
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