Introduction
The traditional diet-heart hypothesis, predicts that the serum cholesterol lowering effects of replacing saturated fat with vegetable oil rich in linoleic acid will diminish deposition of cholesterol in the arterial wall, slow progression of atherosclerosis, reduce coronary heart disease events, and improve survival.

This diet-heart paradigm is supported by, evidence from randomized controlled trials, showing that replacement of saturated fat with linoleic acid lowers serum total cholesterol and low density lipoprotein
and by, observational evidence linking serum cholesterol to coronary heart disease events and deaths .

Despite these compelling relations, no randomized controlled trial has shown that replacement of saturated fat with linoleic acid significantly reduces coronary heart disease events or deaths .

Re-evaluation of the traditional diet-heart hypothesis: analysis of recovered data from Minnesota Coronary Experiment (1968-73)
(Published 12 April 2016)
Cite this as: BMJ 2016;353:i1246

Objective;
To examine the traditional diet-heart hypothesis through recovery and analysis of previously unpublished data from the Minnesota Coronary Experiment (MCE) and to put findings in the context of existing diet-heart randomized controlled trials through a systematic review and meta-analysis.

Design The MCE (1968-73) is a double blind randomized controlled trial designed to test whether replacement of saturated fat with vegetable oil rich in linoleic acid reduces coronary heart disease and death by lowering serum cholesterol.
Recovered MCE unpublished documents and raw data were analyzed according to hypotheses prespecified by original investigators.
Further, a systematic review and meta-analyses of randomized controlled trials that lowered serum cholesterol by providing vegetable oil rich in linoleic acid in place of saturated fat without confounding by concomitant interventions was conducted.

Setting :One nursing home and six state mental hospitals in Minnesota, United States.

Participants Unpublished documents with completed analyses for the randomized cohort of 9423 women and men aged 20-97; longitudinal data on serum cholesterol for the 2355 participants exposed to the study diets for a year or more; 149 completed autopsy files.

Interventions
Serum cholesterol lowering diet that replaced saturated fat with linoleic acid (from corn oil and corn oil polyunsaturated margarine). Control diet was high in saturated fat from animal fats, common margarines, and shortenings.

Main outcome measures
Death from all causes; association between changes in serum cholesterol and death; and coronary atherosclerosis and myocardial infarcts detected at autopsy.

Results
The intervention group had significant reduction in serum cholesterol compared with controls (mean change from baseline ?13.8% v ?1.0%; P<0.001).
Kaplan Meier graphs showed no mortality benefit for the intervention group in the full randomized cohort or for any prespecified subgroup.
There was a 22% higher risk of death for each 30 mg/dL (0.78 mmol/L) reduction in serum cholesterol in covariate adjusted Cox regression models (hazard ratio 1.22, 95% confidence interval 1.14 to 1.32; P<0.001).
There was no evidence of benefit in the intervention group for coronary atherosclerosis or myocardial infarcts.

Systematic review identified five randomized controlled trials for inclusion (n=10?808). In meta-analyses, these cholesterol lowering interventions showed no evidence of benefit on mortality from coronary heart disease (1.13, 0.83 to 1.54) or all cause mortality (1.07, 0.90 to 1.27).

Conclusions
Available evidence from randomized controlled trials shows that replacement of saturated fat in the diet with linoleic acid effectively lowers serum cholesterol but does not support the hypothesis that this translates to a lower risk of death from coronary heart disease or all causes.

Findings from the Minnesota Coronary Experiment add to growing evidence that incomplete publication has contributed to overestimation of the benefits of replacing saturated fat with vegetable oils rich in linoleic acid.

G Mohan