Christopher E Ramsden, Daisy Zamora, Boonseng Leelarthaepin, Sharon F Majchrzak-Hong, Keturah R Faurot, Chirayath M Suchindran, Amit Ringel, John M Davis, Joseph R Hibbeln
Journal: BMJ (Clinical research ed.) 2013;346():e8707
PMID: 23386268
It has already been shown that replacing saturated fatty acids (SFA) with omega 6 (n-6) linoleic acid (LA) can reduce low density lipoproteins (LDL) which is hypothesised to reduce the risk of cardiovascular disease. However, this study looked at the prevention of secondary heart disease and mortality in recovered data from a single-blinded, parallel group, randomised controlled trial carried out between 1966-1973 which replaced dietary SFAs with n-6 polyunsaturated fatty acids (PUFAs) derived from safflower oil. This study also used this recovered data to update their meta-analysis published in 2010. The study was of 458 men who had suffered a recent coronary event and measured mortality over the 7 year period. Results showed a significant reduction in total cholesterol in the intervention group, however, it showed an increase in mortality. The study concluded that the mechanism of cardiovascular disease is independent of cholesterol levels which contradicts traditional understanding and worldwide dietary advice. The updated meta-analysis showed no benefit in replacing SFAs for n-6 or PUFAs for cardiovascular health.
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.
DESIGN
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.
SETTING
Ambulatory, coronary care clinic in Sydney, Australia.
PARTICIPANTS
458 men aged 30-59 years with a recent coronary event.
INTERVENTIONS
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.
OUTCOME MEASURES
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.
TRIAL REGISTRATION
Clinical trials NCT01621087.
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