title: Use of dietary linoleic acid for secondary prevention of coronary heart disease and death: evaluation of recovered data from the Sydney Diet Heart Study and updated meta-analysis.
abstract: OBJECTIVE
  To evaluate the effectiveness of replacing dietary saturated fat with omega 6 linoleic acid, for the secondary prevention of coronary heart disease and death.
  
  
  METHODS
  Evaluation of recovered data from the Sydney Diet Heart Study, a single blinded, parallel group, randomized controlled trial conducted in 1966-73; and an updated meta-analysis including these previously missing data.
  
  
  METHODS
  Ambulatory, coronary care clinic in Sydney, Australia.
  
  
  METHODS
  458 men aged 30-59 years with a recent coronary event.
  
  
  METHODS
  Replacement of dietary saturated fats (from animal fats, common margarines, and shortenings) with omega 6 linoleic acid (from safflower oil and safflower oil polyunsaturated margarine). Controls received no specific dietary instruction or study foods. All non-dietary aspects were designed to be equivalent in both groups.
  
  
  METHODS
  All cause mortality (primary outcome), cardiovascular mortality, and mortality from coronary heart disease (secondary outcomes). We used an intention to treat, survival analysis approach to compare mortality outcomes by group.
  
  
  RESULTS
  The intervention group (n=221) had higher rates of death than controls (n=237) (all cause 17.6% v 11.8%, hazard ratio 1.62 (95% confidence interval 1.00 to 2.64), P=0.05; cardiovascular disease 17.2% v 11.0%, 1.70 (1.03 to 2.80), P=0.04; coronary heart disease 16.3% v 10.1%, 1.74 (1.04 to 2.92), P=0.04). Inclusion of these recovered data in an updated meta-analysis of linoleic acid intervention trials showed non-significant trends toward increased risks of death from coronary heart disease (hazard ratio 1.33 (0.99 to 1.79); P=0.06) and cardiovascular disease (1.27 (0.98 to 1.65); P=0.07).
  
  
  CONCLUSIONS
  Advice to substitute polyunsaturated fats for saturated fats is a key component of worldwide dietary guidelines for coronary heart disease risk reduction. However, clinical benefits of the most abundant polyunsaturated fatty acid, omega 6 linoleic acid, have not been established. In this cohort, substituting dietary linoleic acid in place of saturated fats increased the rates of death from all causes, coronary heart disease, and cardiovascular disease. An updated meta-analysis of linoleic acid intervention trials showed no evidence of cardiovascular benefit. These findings could have important implications for worldwide dietary advice to substitute omega 6 linoleic acid, or polyunsaturated fats in general, for saturated fats.
  
  
  BACKGROUND
  Clinical trials NCT01621087.
authors: Laboratory of Membrane Biophysics and Biochemistry, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA. Chris.Ramsden@nih.gov
authors: Christopher E
authors: CE
authors: Ramsden
authors: Daisy
authors: D
authors: Zamora
authors: Boonseng
authors: B
authors: Leelarthaepin
authors: Sharon F
authors: SF
authors: Majchrzak-Hong
authors: Keturah R
authors: KR
authors: Faurot
authors: Chirayath M
authors: CM
authors: Suchindran
authors: Amit
authors: A
authors: Ringel
authors: John M
authors: JM
authors: Davis
authors: Joseph R
authors: JR
authors: Hibbeln
mesh_terms: D000328:Adult; D003327:Coronary Disease / Q000178:diet therapy / Q000401:mortality / Q000517:prevention & control*; D018752:Diet, Fat-Restricted / Q000379:methods; D004041:Dietary Fats / Q000009:adverse effects; D004812:Epidemiologic Methods; D006801:Humans; D019787:Linoleic Acid / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009517:New South Wales / Q000453:epidemiology; D010938:Plant Oils / Q000008:administration & dosage*; D055502:Secondary Prevention / Q000379:methods*
chemical_list: D004041:Dietary Fats; D010938:Plant Oils; D019787:Linoleic Acid
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