BMJ. 2013 Feb 4;346:e8707. doi: 10.1136/bmj.e8707.
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.
Ramsden CE, Zamora D, Leelarthaepin B, Majchrzak-Hong SF, Faurot KR, Suchindran CM, Ringel A, Davis JM, Hibbeln JR.
Source
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
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.
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.
PMID: 23386268 [PubMed - indexed for MEDLINE]