Heme iron may contribute to the development of atherosclerosis by catalyzing production of hydroxyl-free radicals and promoting low-density lipoprotein oxidation. However, epidemiologic findings regarding the association between heme iron intake and risk of coronary heart disease (CHD) are inconsistent. We aimed to investigate the association by carrying out a meta-analysis of prospective studies.
Relevant studies were identified by using PubMed and EMBASE databases between January 1966 and April 2013 and also by manually reviewing the reference lists of retrieved publications. Summary relative risks (RRs) with corresponding 95 % confidence intervals (CIs) were computed using a random-effects model.
Six prospective studies, which contained a total of 131,553 participants and 2,459 CHD cases, met the inclusion criteria. Combined results indicated that participants with higher heme iron intake had a 31 % increased risk of CHD, compared with those with lower intake (RR = 1.31, 95 % CI 1.04–1.67), with significant heterogeneity (P heterogeneity = 0.05, I 2 = 55.0 %). Excluding the only study from Japan (limiting to Western studies) yielded a RR of 1.46 (95 % CI 1.21–1.76), with no study heterogeneity (P heterogeneity = 0.44, I 2 = 0.0 %). The dose–response RR of CHD for an increase in heme iron intake of 1 mg/day was 1.27 (95 % CI 1.10–1.47), with low heterogeneity (P heterogeneity = 0.25, I 2 = 25.8 %). We observed no significant publication bias.
This meta-analysis suggests that heme iron intake was associated with an increased risk of CHD.
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de Valk B, Marx JJ (1999) Iron, atherosclerosis, and ischemic heart disease. Arch Intern Med 159:1542–1548
Sullivan JL (1981) Iron and the sex difference in heart disease risk. Lancet 1:1293–1294
Gupta R, Rastogi S, Nagar R, Kastia S, Kaul V (2000) Dietary and serum iron, body iron stores and coronary heart disease. J Assoc Physicians India 48:489–492
Reunanen A, Takkunen H, Knekt P, Seppanen R, Aromaa A (1995) Body iron stores, dietary iron intake and coronary heart disease mortality. J Intern Med 238:223–230
Tavani A, Gallus S, Bosetti C, Parpinel M, Negri E, La Vecchia C (2006) Dietary iron intake and risk of non-fatal acute myocardial infarction. Public Health Nutr 9:480–484
Ascherio A, Willett WC, Rimm EB, Giovannucci EL, Stampfer MJ (1994) Dietary iron intake and risk of coronary disease among men. Circulation 89:969–974
Casiglia E, Tikhonoff V, Bascelli A, Giordano N, Caffi S, Andreatta E, Mazza A, Boschetti G, Grasselli C, Saugo M, Rigoni G, Spinella P, Palatini P (2011) Dietary iron intake and cardiovascular outcome in Italian women: 10-year follow-up. J Womens Health (Larchmt) 20:1565–1571
Klipstein-Grobusch K, Grobbee DE, den Breeijen JH, Boeing H, Hofman A, Witteman JC (1999) Dietary iron and risk of myocardial infarction in the Rotterdam study. Am J Epidemiol 149:421–428
Qi L, van Dam RM, Rexrode K, Hu FB (2007) Heme iron from diet as a risk factor for coronary heart disease in women with type 2 diabetes. Diabetes Care 30:101–106
van der A DL, Peeters PH, Grobbee DE, Marx JJ, van der Schouw YT (2005) Dietary haem iron and coronary heart disease in women. Eur Heart J 26:257–262
Zhang W, Iso H, Ohira T, Date OC, Tanabe N, Kikuchi S, Tamakoshi A (2012) Associations of dietary iron intake with mortality from cardiovascular disease: the JACC study. J Epidemiol 22:484–493
Cook JD (1990) Adaptation in iron metabolism. Am J Clin Nutr 51:301–308
Carpenter CE, Mahoney AW (1992) Contributions of heme and nonheme iron to human nutrition. Crit Rev Food Sci Nutr 31:333–367
Hambraeus L (1999) Animal- and plant-food-based diets and iron status: benefits and costs. Proc Nutr Soc 58:235–242
de Oliveira Otto MC, Alonso A, Lee DH, Delclos GL, Bertoni AG, Jiang R, Lima JA, Symanski E, Jacobs DR Jr, Nettleton JA (2012) Dietary intakes of zinc and heme iron from red meat, but not from other sources, are associated with greater risk of metabolic syndrome and cardiovascular disease. J Nutr 142:526–533
Lee DH, Folsom AR, Jacobs DR Jr (2005) Iron, zinc, and alcohol consumption and mortality from cardiovascular diseases: the Iowa Women’s Health Study. Am J Clin Nutr 81:787–791
DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188
Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558
Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634
Greenland S, Longnecker MP (1992) Methods for trend estimation from summarized dose-response data, with applications to meta-analysis. Am J Epidemiol 135:1301–1309
Orsini N, Bellocco R, Greenland S (2006) Generalized least squares for trend estimation of summarized dose-response data. Stata J 6:40–57
Hara A, Sasazuki S, Inoue M, Iwasaki M, Shimazu T, Sawada N, Yamaji T, Takachi R, Tsugane S (2012) Zinc and heme iron intakes and risk of colorectal cancer: a population-based prospective cohort study in Japan. Am J Clin Nutr 96:864–873
Sun Q, Shi L, Rimm EB, Giovannucci EL, Hu FB, Manson JE, Rexrode KM (2011) Vitamin D intake and risk of cardiovascular disease in US men and women. Am J Clin Nutr 94:534–542
Kromhout D (2012) Omega-3 fatty acids and coronary heart disease. The final verdict? Curr Opin Lipidol 23:554–559
Tappel A (2007) Heme of consumed red meat can act as a catalyst of oxidative damage and could initiate colon, breast and prostate cancers, heart disease and other diseases. Med Hypotheses 68:562–564
de Oliveira Otto MC, Alonso A, Lee DH, Delclos GL, Jenny NS, Jiang R, Lima JA, Symanski E, Jacobs DR Jr, Nettleton JA (2011) Dietary micronutrient intakes are associated with markers of inflammation but not with markers of subclinical atherosclerosis. J Nutr 141:1508–1515
Jiang R, Manson JE, Meigs JB, Ma J, Rifai N, Hu FB (2004) Body iron stores in relation to risk of type 2 diabetes in apparently healthy women. JAMA 291:711–717
Tzoulaki I, Brown IJ, Chan Q, Van Horn L, Ueshima H, Zhao L, Stamler J, Elliott P (2008) Relation of iron and red meat intake to blood pressure: cross sectional epidemiological study. BMJ 337:a258
Clarke R, Shipley M, Lewington S, Youngman L, Collins R, Marmot M, Peto R (1999) Underestimation of risk associations due to regression dilution in long-term follow-up of prospective studies. Am J Epidemiol 150:341–353
Thornton A, Lee P (2000) Publication bias in meta-analysis: its causes and consequences. J Clin Epidemiol 53:207–216
Higgins JP, Green S, Collaboration C (2008) Cochrane handbook for systematic reviews of interventions. Wiley Online Library, United States
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The authors declare that they have no conflict of interest.
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Yang, W., Li, B., Dong, X. et al. Is heme iron intake associated with risk of coronary heart disease? A meta-analysis of prospective studies. Eur J Nutr 53, 395–400 (2014). https://doi.org/10.1007/s00394-013-0535-5