Risk of cardiovascular disease-related and all-cause death according to serum concentrations of enterolactone: Kuopio Ischaemic Heart Disease Risk Factor Study

Arch Intern Med. 2003 May 12;163(9):1099-104. doi: 10.1001/archinte.163.9.1099.


Background: Enterolactone is a plant-derived compound that has been associated with a reduced risk of acute coronary events and cancer. Several studies have suggested that serum enterolactone concentration may play a role as a biomarker of a diet high in fiber and vegetables. Owing to its phenolic structure, enterolactone and its plant lignan precursors, which are converted by intestinal bacteria to enterolactone, are potential antioxidants.

Methods: The associations between serum enterolactone level and the risk of coronary heart disease (CHD)-related, cardiovascular disease (CVD)-related, and all-cause mortality were investigated in the Kuopio Ischaemic Heart Disease Risk Factor Study, which is a prospective population-based study of middle-aged Finnish men. The serum enterolactone concentration and cardiovascular risk factors were determined in 1889 men aged 42 to 60 years. In an average follow-up of 12.2 years, 70 CHD-related, 103 CVD-related, and 242 all-cause deaths occurred in participants free of prior CVD.

Results: Multivariate analyses showed significant associations between elevated serum enterolactone concentration and reduced risk of CHD- and CVD-related mortality, but weaker associations in relation to all-cause mortality. In the Cox proportional hazards regression model adjusting for the most potent confounding factors, the risk of CHD-related (P =.03 for trend) and CVD-related (P =.04 for trend) death decreased linearly across quartiles of serum enterolactone concentration.

Conclusions: Our data suggest that a high serum enterolactone level is associated with reduced CHD- and CVD-related mortality in middle-aged Finnish men. These results add to the evidence supporting the importance of whole grain foods, fruits, and vegetables in the prevention of premature death from CVD.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 4-Butyrolactone / analogs & derivatives*
  • 4-Butyrolactone / blood*
  • Adult
  • Cause of Death
  • Finland / epidemiology
  • Follow-Up Studies
  • Humans
  • Lignans / blood*
  • Male
  • Middle Aged
  • Myocardial Ischemia / blood
  • Myocardial Ischemia / mortality*
  • Prospective Studies
  • Risk Assessment
  • Risk Factors


  • Lignans
  • 4-Butyrolactone
  • 2,3-bis(3'-hydroxybenzyl)butyrolactone