LETTER
Iron, Oxidative Stress, and the Mediterranean Diet To the Editor: Dalen and Devries1 outlined that dietary patterns consistent with the traditional Mediterranean-style diet are particularly cardioprotective. These findings invite further consideration of mechanisms.2 The balance between the average bioavailability of dietary iron and the overall actions of inhibitors and enhancers of iron absorption may lead to lower iron stores in people consuming a Mediterranean dietary pattern.3 This effect might be related to reduced risk of cardiovascular disease, as confirmed in a prospective randomized clinical trial of iron reduction.4 Redox-active iron generates hydroxyl ions capable of damaging cells and critical biomolecules. Such reactivity likely accounts for involvement of iron on plaque destabilization.5 In late adolescence, men begin a steady accumulation of storage iron with age, but women fail to acquire significant iron stores because of their continual losses of iron in menstrual blood, pregnancies, and deliveries. An escalation of risk follows initial acquisition of significant stored iron after cessation of menses because of natural menopause or surgical removal of the uterus or ovaries. The amount of free iron available at sites of oxidative or inflammatory injury seems to be a function of the stored iron level. Removal of stored iron from the body by phlebotomy, systemic iron chelation treatment, or dietary iron restriction has been shown to decrease the amount of iron deposition within atherosclerotic lesions in animal studies. Tests of the iron hypothesis for Mediterranean diet effects in the United States may be difficult because of population-wide involuntary ingestion of nonphysiologic Funding: None. Conflict of Interest: None. Authorship: All authors had access to the data and played a role in writing this manuscript.
0002-9343/$ -see front matter Ó 2014 Elsevier Inc. All rights reserved.
supplemental iron, such as the ingestion of iron-containing vitamin and mineral products and food supplements that are a major contributor to increasing iron stores with aging.6 The prospect of safe, effective, and low-cost disease prevention and treatment may be at hand but unachievable for lack of awareness of cause-and-effect relationships and risks of unnecessary iron supplement ingestion.5,7 Luca Mascitelli, MDa Mark R. Goldstein, MDb Leo R. Zacharski, MDc,d Comando Brigata alpina “Julia”/Multinational Land Force, Medical Service Udine, Italy b NCH Physicians Group Naples, Fla c Research Service, Veterans Affairs Hospital White River Junction, Vt d Geisel School of Medicine, Department of Medicine Dartmouth College Hanover, NH a
http://dx.doi.org/10.1016/j.amjmed.2014.05.039
References 1. Dalen JE, Devries S. Diets to prevent coronary heart disease 1957-2013: what have we learned? Am J Med. 2014;127:364-369. 2. Mascitelli L, Goldstein MR. Mediterranean diet, lower body iron stores and metabolic syndrome. Int J Clin Pract. 2011;65:1110. 3. Buijsse B, Feskens EJ, Moschandreas J, et al. Oxidative stress, and iron and antioxidant status in elderly men: differences between the Mediterranean south (Crete) and northern Europe (Zutphen). Eur J Cardiovasc Prev Rehabil. 2007;14:495-500. 4. Zacharski LR, Shamayeva G, Chow BK. Effect of controlled reduction of body iron stores on clinical outcomes in peripheral arterial disease. Am Heart J. 2011;162:949-957. 5. Zacharski LR, Depalma RG, Shamayeva G, Chow BK. The statin-iron nexus: anti-inflammatory intervention for arterial disease prevention. Am J Public Health. 2013;103:e105-e112, Erratum in: Am J Public Health. 2013;103:e9. 6. Fleming DJ, Tucker KL, Jacques PF, Dallal GE, Wilson PW, Wood RJ. Dietary factors associated with the risk of high iron stores in the elderly Framingham Heart Study cohort. Am J Clin Nutr. 2002;76:1375-1384. 7. Ferrotoxic disease: quantitative effects of iron excess on health. Available at: www.healtheiron.com. Accessed May 10, 2014.
Iron, Oxidative Stress, and the Mediterranean Diet To the Editor: Dalen and Devries1 outlined that dietary patterns consistent with the traditional Mediterranean-style diet are particularly cardioprotective. These findings invite further consideration of mechanisms.2 The balance between the average bioavailability of dietary iron and the overall actions of inhibitors and enhancers of iron absorption may lead to lower iron stores in people consuming a Mediterranean dietary pattern.3 This effect might be related to reduced risk of cardiovascular disease, as confirmed in a prospective randomized clinical trial of iron reduction.4 Redox-active iron generates hydroxyl ions capable of damaging cells and critical biomolecules. Such reactivity likely accounts for involvement of iron on plaque destabilization.5 In late adolescence, men begin a steady accumulation of storage iron with age, but women fail to acquire significant iron stores because of their continual losses of iron in menstrual blood, pregnancies, and deliveries. An escalation of risk follows initial acquisition of significant stored iron after cessation of menses because of natural menopause or surgical removal of the uterus or ovaries. The amount of free iron available at sites of oxidative or inflammatory injury seems to be a function of the stored iron level. Removal of stored iron from the body by phlebotomy, systemic iron chelation treatment, or dietary iron restriction has been shown to decrease the amount of iron deposition within atherosclerotic lesions in animal studies. Tests of the iron hypothesis for Mediterranean diet effects in the United States may be difficult because of population-wide involuntary ingestion of nonphysiologic Funding: None. Conflict of Interest: None. Authorship: All authors had access to the data and played a role in writing this manuscript.
0002-9343/$ -see front matter Ó 2014 Elsevier Inc. All rights reserved.
supplemental iron, such as the ingestion of iron-containing vitamin and mineral products and food supplements that are a major contributor to increasing iron stores with aging.6 The prospect of safe, effective, and low-cost disease prevention and treatment may be at hand but unachievable for lack of awareness of cause-and-effect relationships and risks of unnecessary iron supplement ingestion.5,7 Luca Mascitelli, MDa Mark R. Goldstein, MDb Leo R. Zacharski, MDc,d Comando Brigata alpina “Julia”/Multinational Land Force, Medical Service Udine, Italy b NCH Physicians Group Naples, Fla c Research Service, Veterans Affairs Hospital White River Junction, Vt d Geisel School of Medicine, Department of Medicine Dartmouth College Hanover, NH a
http://dx.doi.org/10.1016/j.amjmed.2014.05.039
References 1. Dalen JE, Devries S. Diets to prevent coronary heart disease 1957-2013: what have we learned? Am J Med. 2014;127:364-369. 2. Mascitelli L, Goldstein MR. Mediterranean diet, lower body iron stores and metabolic syndrome. Int J Clin Pract. 2011;65:1110. 3. Buijsse B, Feskens EJ, Moschandreas J, et al. Oxidative stress, and iron and antioxidant status in elderly men: differences between the Mediterranean south (Crete) and northern Europe (Zutphen). Eur J Cardiovasc Prev Rehabil. 2007;14:495-500. 4. Zacharski LR, Shamayeva G, Chow BK. Effect of controlled reduction of body iron stores on clinical outcomes in peripheral arterial disease. Am Heart J. 2011;162:949-957. 5. Zacharski LR, Depalma RG, Shamayeva G, Chow BK. The statin-iron nexus: anti-inflammatory intervention for arterial disease prevention. Am J Public Health. 2013;103:e105-e112, Erratum in: Am J Public Health. 2013;103:e9. 6. Fleming DJ, Tucker KL, Jacques PF, Dallal GE, Wilson PW, Wood RJ. Dietary factors associated with the risk of high iron stores in the elderly Framingham Heart Study cohort. Am J Clin Nutr. 2002;76:1375-1384. 7. Ferrotoxic disease: quantitative effects of iron excess on health. Available at: www.healtheiron.com. Accessed May 10, 2014.
