Factors associated with serum ferritin levels and iron excess: results from the EPIC-EurGast study

Eur J Nutr. 2022 Feb;61(1):101-114. doi: 10.1007/s00394-021-02625-w. Epub 2021 Jul 2.


Purpose: Excess iron is involved in the development of non-communicable diseases such as cancer, type 2 diabetes and cardiovascular conditions. We aimed to describe the prevalence of excess iron and its determinants in healthy European adults.

Methods: Sociodemographic, lifestyle, iron status, dietary information, and HFE genotyping were obtained from controls from the nested case-control study EPIC-EurGast study. High sensitivity C-reactive protein (hsCRP) was measured to address possible systemic inflammation. Descriptive and multivariate analyses were used to assess iron status and its determinants.

Results: Out of the 828 participants (median age: 58.7 years), 43% were females. Median serum ferritin and prevalence of excess iron were 143.7 µg/L and 35.2% in males, respectively, and 77 µg/L and 20% in females, both increasing with latitude across Europe. Prevalence of HFE C282Y mutation was significantly higher in Northern and Central Europe (~ 11%) than in the South (5%). Overweight/obesity, age, and daily alcohol and heme iron intake were independent determinants for iron status, with sex differences even after excluding participants with hsCRP > 5 mg/L. Obese males showed a greater consumption of alcohol, total and red meat, and heme iron, compared with those normal weight.

Conclusion: Obesity, higher alcohol and heme iron consumption were the main risk factors for excess iron in males while only age was associated with iron overload in females. Weight control and promoting healthy lifestyle may help prevent iron overload, especially in obese people. Further research is needed to clarify determinants of excess iron in the healthy adult population, helping to reduce the associated comorbidities.

Keywords: EPIC; Excess iron; Iron overload; Iron status; Serum ferritin.

MeSH terms

  • Case-Control Studies
  • Diabetes Mellitus, Type 2*
  • Female
  • Ferritins
  • Hemochromatosis Protein / genetics
  • Hemochromatosis* / epidemiology
  • Hemochromatosis* / genetics
  • Histocompatibility Antigens Class I
  • Humans
  • Iron
  • Iron Overload*
  • Male
  • Middle Aged


  • Hemochromatosis Protein
  • Histocompatibility Antigens Class I
  • Ferritins
  • Iron