The Minnesota Coronary Experiment re-analysis by Ramsden et al is a wake-call to re-evaluate the use of polyunsaturated oils and spreads in modern clinical diets?
The analysis of recovered data from the Minnesota Coronary Experiment by Ramsden et al has revealed results consistent with other analyses of diet-heart RCTs that excluded trials involving confounding by mixed interventions, that the experimental lowering of saturated fat results in no reduction in cardiovascular or all-cause mortality.[1,2,]
The possible adverse effect of the intervention in elderly subjects described by Ramsden et al is also consistent with observational studies of cholesterol and mortality risk in the elderly, including a study in which changes in cholesterol were tracked. Elderly subjects with low cholesterol whose cholesterol remained low in subsequent tests had the highest mortality; those in whom cholesterol increased again were not exposed to increased risk. With all that has long been known about the correlations between cholesterol and risk in the elderly, it is not frivolous to ask why an intervention intended to raise cholesterol by replacing an unhealthful food (such as corn oil) with a healthful food rich in saturated fat (such as sour cream) has never been trialed.
The recent results from the EPIC-Netherlands prospective observational study of 35,597 subjects followed for 12 years describe a population in which the consumption of higher intakes of dairy fat is associated with a lower risk of ischemic heart disease (IHD). An energy substitution analysis based on the EPIC-N data even predicts that the replacement of energy from dairy saturated fat with energy from monounsaturated or polyunsaturated fat will increase IHD risk.
One suspects that had the diet-heart hypothesis been delayed until the 21st century, its postulates may just as easily been the inverse of the traditional ones, and that dairy fats and fish oils, which do not generally lower cholesterol, might have been emphasized.
Although studies that seem to support the diet-heart hypothesis have always been published early and often, the null result from the Minnesota Coronary Experiment was not published for 16 years, until well after dietary guidelines to lower saturated fat became fixed. However, Ancel Keys was aware of the result by 1973. This passage in the 1980 Seven Countries Study, for which Keys was the lead author, seems to have largely escaped the notice of those promoting refined oils and spreads.
“The coronary incidence rate of the cohorts was not significantly correlated with the percentage of calories in the diet provided by proteins or by polyunsaturated fatty acids. In regard to the latter, the averages for the cohorts ranged from 3 percent to seven percent of calories from linoleic acid, with only trivial contributions from other polyenes. These findings conform to the general picture that in no natural diet of man so far studied do polyunsaturated fatty acids contribute more than a very small fraction of the total calories. Accordingly, it must be expected that in such natural diets variations in the amount of polyunsaturated fatty acids will have at most only a trivial effect on the concentration of cholesterol in the blood serum or risk associated with it.”
The questions raised by Marsden et al are not merely ones of historical interest. Whatever the classical causes of heart disease, the risk today is increasingly one associated with diabetes, overweight, and non-alcoholic fatty liver disease. Low carbohydrate, high fat (LCHF) diets are one of the most effective interventions for these conditions and tend to produce beneficial changes in multiple metabolic risk factors, predicting long-term lowering of cardiovascular risk, in these patients. However, many clinical LCHF interventions are also reduced saturated-fat interventions, and some of these may use levels of linoleic acid comparable to that in the MSE study. There is a scarcity of evidence that saturated fat restriction or an intake of linoleic acid beyond the natural range described by Keys et al produces superior metabolic benefits in LCHF diet trials. A comparative meta-analysis of the trial data that bears on this question would be welcomed.
Essential fatty acids are essential, but they are available in all naturally fatty foods, a grouping which does not usually include corn or soy. It is questionable in nutritional terms whether anyone who eats a high-fat diet which includes some of the natural sources of linoleic acid - nuts, seeds, meat, lard, fish and dairy - can ever benefit from an even higher intake via the replacement of any of these foods with refined oils and spreads. No-one has yet proved that there is anything wrong with a nutritious diet of real foods which have been minimally processed and refined, and we suggest that the default prescription for any test of a diet and disease hypothesis in future should be a diet of foods with a low Human Interference Factor (HIF), rather than foods that can only be produced by industrial processing, such as corn oil.
 Hooper L, Summerbell CD, Thompson R, Sills D, Roberts FG, Moore HJ, Davey Smith G. Reduced or modified dietary fat for preventing cardiovascular disease. Cochrane Database Syst Rev. 2012 May 16;5:CD002137.
 Hooper L, Martin N, Abdelhamid A, Davey Smith G. Reduction in saturated fat intake for cardiovascular disease. Cochrane Database Syst Rev. 2015 Jun 10;6:CD011737.
 Schatz IJ, Masaki K, Yano K, Chen R, Rodriguez BL, Curb JD. Cholesterol and all-cause mortality in elderly people from the Honolulu Heart Program: a cohort study. Lancet. 2001 Aug 4;358(9279):351-5.
 Praagman J, Beulens JW, Alssema M, Zock PL, Wanders AJ4, Sluijs I, van der Schouw YT. The association between dietary saturated fatty acids and ischemic heart disease depends on the type and source of fatty acid in the European Prospective Investigation into Cancer and Nutrition-Netherlands cohort. Am J Clin Nutr. 2016 Feb;103(2):356-65. doi: 10.3945/ajcn.115.122671. Epub 2016 Jan 20.
 Keys, A., Aravanis, C., Blackburn, H., Buzina, R., Djordjević, B.S., Dontas, A.S., Fidanza, F., Karvonen, M.J., Kimura, N., Menotti, A. et al. Seven Countries. A Multivariate Analysis of Death and Coronary Heart Disease. p253 ch14. 1980. Harvard University Press, Cambridge, Massachusetts.
 Schofield G, Henderson G, Thornley S, Crofts C. Very low-carbohydrate diets in the management of diabetes revisited. NZMJ. 2016;129(1432).
Competing interests: No competing interests