Dietary intake of heme iron and risk of cardiovascular disease: a dose-response meta-analysis of prospective cohort studies

Nutr Metab Cardiovasc Dis. 2015 Jan;25(1):24-35. doi: 10.1016/j.numecd.2014.09.002. Epub 2014 Sep 30.


Background and aims: Iron is thought to play a fundamentally important role in the development of cardiovascular disease (CVD). This meta-analysis was performed to investigate the dose-response association between dietary intake of iron (including heme and non-heme iron) and the risk of CVD.

Methods and results: We performed a search of the PubMed and Embase databases for prospective cohort studies of the association between dietary iron intake and CVD risk. Thirteen articles comprising 252,164 participants and 15,040 CVD cases were eligible for inclusion. Heme iron intake was associated significantly with increased risk of cardiovascular disease, and the pooled relative risk (RR) for each 1 mg/day increment was 1.07 (95% confidence interval: 1.01 to 1.14, I² = 59.7%). We also found evidence of a curvilinear association (P < 0.05 for non-linearity). In contrast, we found no association between CVD risk and dietary non-heme (0.98, 0.96 to 1.01, I² = 15.8%) or total iron (1.00, 0.94 to 1.06, I² = 30.4%). Subgroup analyses revealed that the association between heme iron intake and CVD risk was stronger among non-fatal cases (1.19, 1.07-1.33) and American patients (1.31, 1.11-1.56).

Conclusions: Higher dietary intake of heme iron is associated with an increased risk of cardiovascular disease, whereas no association was found between CVD and non-heme iron intake or total iron intake. These findings may have important public health implications with respect to preventing cardiovascular disease.

Keywords: Cardiovascular disease; Dose–response; Heme iron; Meta-analysis.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / etiology*
  • Dietary Supplements / adverse effects
  • Evidence-Based Medicine*
  • Heme / administration & dosage
  • Heme / adverse effects*
  • Humans
  • Iron, Dietary / administration & dosage
  • Iron, Dietary / adverse effects*
  • Meat / adverse effects
  • Risk Factors


  • Iron, Dietary
  • Heme