Is heme iron intake associated with risk of coronary heart disease? A meta-analysis of prospective studies

Eur J Nutr. 2014;53(2):395-400. doi: 10.1007/s00394-013-0535-5. Epub 2013 May 26.


Purpose: 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.

Methods: 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.

Results: 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.

Conclusions: This meta-analysis suggests that heme iron intake was associated with an increased risk of CHD.

Publication types

  • Meta-Analysis

MeSH terms

  • Adult
  • Aged
  • Coronary Disease / chemically induced*
  • Female
  • Fluoresceins
  • Heme / chemistry*
  • Humans
  • Hydroxyl Radical / chemistry
  • Iron / administration & dosage
  • Iron / adverse effects*
  • Lipoproteins, LDL / chemistry
  • Male
  • Middle Aged
  • Ouabain / analogs & derivatives
  • Prospective Studies
  • Risk Factors


  • Fluoresceins
  • Lipoproteins, LDL
  • rhodol green-ethylenediamine-ouabain
  • Hydroxyl Radical
  • Heme
  • Ouabain
  • Iron