The iron hypothesis--does iron cause atherosclerosis?

Women experience only 30-50% of the coronary heart disease (CHD) incidence and mortality of age-matched men. Since oxidation of low-density lipoprotein (LDL) cholesterol is important in atherosclerosis, and oxidation is catalyzed by iron, it has been hypothesized that the lower iron stores of women reduce their risk of CHD through lessened lipid peroxide. The biochemistry of oxidation is well described in the literature and involves iron as a catalyst in the formation of powerful free radicals which subsequently modify LDL cholesterol. Chelating iron with desferrioxamine stops oxidation. Iron is present in atherosclerotic gruel and this gruel stimulates lipid peroxidation. Serum deficient in iron has minimal oxidative capacity which increases with iron repletion. At least seven epidemiologic studies have found a positive association between CHD and various indicators of body iron. Conversely 18 epidemiologic studies have found a negative or no association. While biochemically appealing, the iron hypothesis remains unproven.