The effect of replacing saturated fat with mostly n-6 polyunsaturated fat on coronary heart disease: a meta-analysis of randomised controlled trials

Nutr J. 2017 May 19;16(1):30. doi: 10.1186/s12937-017-0254-5.


Background: A cornerstone of conventional dietary advice is the recommendation to replace saturated fatty acids (SFA) with mostly n-6 polyunsaturated fatty acids (PUFA) to reduce the risk of coronary heart disease (CHD). Many clinical trials aimed to test this advice and have had their results pooled in several meta-analyses. However, earlier meta-analyses did not sufficiently account for major confounding variables that were present in some of those trials. Therefore, the aim of the study was to account for the major confounding variables in the diet heart trials, and emphasise the results from those trials that most accurately test the effect of replacing SFA with mostly n-6 PUFA.

Design: Clinical trials were identified from earlier meta-analyses. Relevant trials were categorised as 'adequately controlled' or 'inadequately controlled' depending on whether there were substantial dietary or non-dietary differences between the experimental and control groups that were not related to SFA or mostly n-6 PUFA intake, then were subject to different subgroup analyses.

Results: When pooling results from only the adequately controlled trials there was no effect for major CHD events (RR = 1.06, CI = 0.86-1.31), total CHD events (RR = 1.02, CI = 0.84-1.23), CHD mortality (RR = 1.13, CI = 0.91-1.40) and total mortality (RR = 1.07, CI = 0.90-1.26). Whereas, the pooled results from all trials, including the inadequately controlled trials, suggested that replacing SFA with mostly n-6 PUFA would significantly reduce the risk of total CHD events (RR = 0.80, CI = 0.65-0.98, P = 0.03), but not major CHD events (RR = 0.87, CI = 0.70-1.07), CHD mortality (RR = 0.90, CI = 0.70-1.17) and total mortality (RR = 1.00, CI = 0.90-1.10).

Conclusion: Available evidence from adequately controlled randomised controlled trials suggest replacing SFA with mostly n-6 PUFA is unlikely to reduce CHD events, CHD mortality or total mortality. The suggestion of benefits reported in earlier meta-analyses is due to the inclusion of inadequately controlled trials. These findings have implications for current dietary recommendations.

Keywords: Clinical trial; Coronary heart disease; Diet heart hypothesis; Meta-analysis; Omega 6; Polyunsaturated fat; Randomised controlled trial; Saturated fat.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Cholesterol / blood
  • Coronary Disease / epidemiology*
  • Coronary Disease / mortality
  • Diet*
  • Dietary Fats
  • Fatty Acids / administration & dosage*
  • Fatty Acids / blood
  • Fatty Acids, Omega-6 / administration & dosage*
  • Fatty Acids, Omega-6 / blood
  • Humans
  • Observational Studies as Topic
  • Randomized Controlled Trials as Topic
  • Risk Factors


  • Dietary Fats
  • Fatty Acids
  • Fatty Acids, Omega-6
  • Cholesterol