The iron hypothesis--does iron cause atherosclerosis?

Area of Science:

• Biochemistry
• Cardiovascular Science
• Nutritional Science

Background:

• Women exhibit significantly lower incidence and mortality rates of coronary heart disease (CHD) compared to age-matched men.
• Oxidation of low-density lipoprotein (LDL) cholesterol is a key process in atherosclerosis development.
• Iron acts as a catalyst in the oxidation of LDL cholesterol, generating harmful free radicals.

Purpose of the Study:

• To investigate the hypothesis that lower body iron stores in women contribute to their reduced risk of CHD.
• To explore the role of iron-catalyzed lipid peroxidation in the pathogenesis of atherosclerosis.

Main Methods:

• Review of biochemical literature on oxidation processes and iron's role.
• Examination of studies on iron's presence in atherosclerotic lesions and its effect on lipid peroxidation.
• Analysis of epidemiological studies correlating body iron indicators with CHD risk.

Main Results:

• Biochemical pathways demonstrate iron's catalytic role in LDL oxidation; iron chelation inhibits this process.
• Atherosclerotic plaque contains iron, which stimulates lipid peroxidation.
• Epidemiological data presents conflicting evidence, with some studies showing a positive association and others a negative or no association between body iron and CHD.

Conclusions:

• The biochemical rationale linking lower iron stores to reduced CHD risk via decreased LDL oxidation is plausible.
• Despite biochemical evidence, the epidemiological data is inconclusive, and the iron hypothesis for CHD prevention remains unproven.