Interplay between different polyunsaturated fatty acids and risk of coronary heart disease in men

Circulation. 2005 Jan 18;111(2):157-64. doi: 10.1161/01.CIR.0000152099.87287.83. Epub 2005 Jan 3.


Background: Consumption of polyunsaturated fatty acids (PUFAs) may reduce coronary heart disease (CHD) risk, but n-6 PUFAs may compete with n-3 PUFA metabolism and attenuate benefits. Additionally, seafood-based, long-chain n-3 PUFAs may modify the effects of plant-based, intermediate-chain n-3 PUFAs. However, the interactions of these PUFAs in relation to CHD risk are not well established.

Methods and results: Among 45,722 men free of known cardiovascular disease in 1986, usual dietary intake was assessed at baseline and every 4 years by using validated food-frequency questionnaires. CHD incidence was prospectively ascertained. Over 14 years of follow-up, participants experienced 218 sudden deaths, 1521 nonfatal myocardial infarctions (MIs), and 2306 total CHD events (combined sudden death, other CHD deaths, and nonfatal MI). In multivariate-adjusted analyses, both long-chain and intermediate-chain n-3 PUFA intakes were associated with lower CHD risk, without modification by n-6 PUFA intake. For example, men with > or = median long-chain n-3 PUFA intake (> or =250 mg/d) had a reduced risk of sudden death whether n-6 PUFA intake was below (<11.2 g/d; hazard ratio [HR]=0.52; 95% confidence interval [CI]=0.34 to 0.79) or above (> or =11.2 g/d; HR=0.60; 95% CI=0.39 to 0.93) the median compared with men with a < median intake of both. In similar analyses, > or = median intake of intermediate-chain n-3 PUFAs (> or =1080 mg/d) was associated with a reduced total CHD risk whether n-6 PUFA intake was lower (HR=0.88; 95% CI=0.78 to 0.99) or higher (HR=0.89; 95% CI=0.79 to 0.99) compared with a < median intake of both. Intermediate-chain n-3 PUFAs were particularly associated with CHD risk when long-chain n-3 PUFA intake was very low (<100 mg/d); among these men, each 1 g/d of intermediate-chain n-3 PUFA intake was associated with an approximately 50% lower risk of nonfatal MI (HR=0.42; 95% CI=0.23 to 0.75) and total CHD (HR=0.53; 95% CI=0.34 to 0.83).

Conclusions: n-3 PUFAs from both seafood and plant sources may reduce CHD risk, with little apparent influence from background n-6 PUFA intake. Plant-based n-3 PUFAs may particularly reduce CHD risk when seafood-based n-3 PUFA intake is low, which has implications for populations with low consumption or availability of fatty fish.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Coronary Disease / epidemiology
  • Coronary Disease / metabolism*
  • Coronary Disease / prevention & control
  • Death, Sudden, Cardiac / epidemiology
  • Dietary Fats / pharmacokinetics*
  • Drug Interactions
  • Fatty Acids, Omega-3 / pharmacokinetics*
  • Fatty Acids, Omega-6 / pharmacokinetics*
  • Feeding Behavior
  • Fish Oils / pharmacokinetics
  • Follow-Up Studies
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Myocardial Infarction / epidemiology
  • Plant Oils / pharmacokinetics
  • Proportional Hazards Models
  • Prospective Studies
  • Risk
  • Seafood
  • Surveys and Questionnaires
  • alpha-Linolenic Acid / pharmacokinetics


  • Dietary Fats
  • Fatty Acids, Omega-3
  • Fatty Acids, Omega-6
  • Fish Oils
  • Plant Oils
  • alpha-Linolenic Acid