Dietary fats and cardiovascular disease
Ramsden and colleagues conclusions on replacing saturated fat with linoleic acid are not supported by the data. Contrary to their claims, strong and consistent evidence from both randomized clinical trials and prospective observational studies indicate that replacing saturated fat with healthy fats (including n-3 and n-6 polyunsaturated fats) has favorable effects on cardiovascular disease (CVD).
There were major problems with both the design and interpretation of the data from the MCE. The most severe of these are the duration of the trial and the very high rates of dropout. Only ~25% of the study participants received the study diets for more than a year with an average exposure of ~3 years. The short-term duration of the intervention and unusually high rates of non-compliance called the validity of the study into question.
Second, their data on the degree of atherosclerotic progression confirmed through autopsy was on a very small number (n=149). It is highly unlikely for a 1-year intervention to alter plaque that has been built up for decades. In fact, well-known dietary intervention studies such as the Los Angeles Veterans Administration trial1 and the Finnish Mental Hospital trial2 lasted more than 5 years and found that replacing saturated fat with polyunsaturated fats reduced both serum cholesterol and CHD incidence.
Third, the authors found that the excess mortality with the serum cholesterol lowering intervention (“cholesterol paradox”) was primarily confined to patients 65 years and older. Analyses in this sub-sample are plagued by the same issues that we observe with the “obesity paradox3”, where weight loss is often associated with increased mortality in older individuals or hospitalized patients. Also, among those aged ≥65 years, the hazard ratio for death was similar in the intervention group and the control group suggesting that the intervention, per se, had no effect on death.
Fourth, the intervention used in the MCE does not in any way reflect the average American diet. In fact, the level of linoleic acid (13.2%, range: 11.3%-16.5%) in the intervention group is well above the levels consumed by the US population (average 7%).4 It is also important to note that major food sources of linoleic acid such as soybean oil, canola oil, and walnuts also contain substantial amounts of alpha-linolenic acid, a plant-based omega-3 fatty acid.
Fifth, the authors’ meta-analyses looked at CHD mortality, which is not a primary endpoint in many of the trials. The meta-analysis also omitted the Finnish Mental Hospital trial2, an important study with similar levels of linoleic acid intake as the MCE that showed a reduction in both serum cholesterol and cardiovascular events. In fact, a previous meta-analysis, which included the MCE, found significant benefits of replacing saturated fat with polyunsaturated fats on both serum cholesterol and incidence of major cardiovascular events5. The statistical power for analyzing CHD mortality was greatly reduced compared to that for incident CVD events.
Finally, the authors suggest several biological “hypotheses”, including changes to lipoprotein particle oxidation that may have contributed to increased CHD risk in the intervention group. However, this is merely speculative and evidence from randomized clinical trials do not support the role of linoleic acid in increased inflammation.6
In sum, this report is highly misleading and should not alter current dietary recommendations that emphasize healthy sources of fats (including n-3 and n-6 polyunsaturated fatty acids, and plant-based monounsaturated fat) as a replacement for saturated fat in the context of healthy eating patterns.
1. Dayton S, Pearce ML, Hashimoto S, Dixon WJ, Tomiyasu U. A Controlled Clinical Trial of a Diet High in Unsaturated Fat in Preventing Complications of Atherosclerosis. Circulation 1969;40(1 SUPPLEMENT II ): II-1:II-63
2. Turpeinen O, Karvonen MJ, Pekkarinen M, Miettinen M, Elosuo R, Paavilainen E. Dietary prevention of coronary heart disease: the Finnish Mental Hospital Study. International journal of epidemiology 1979;8(2):99-118.
3. Tobias DK, Hu FB. Does being overweight really reduce mortality? Obesity (Silver Spring) 2013;21(9):1746-9.
4. US Department of Agriculture. What We Eat in America, NHANES 2011-2012, individuals 2 years and over (excluding breast-fed children), day 1. Agricultural Research Service, Beltsville Human Nutrition Research Center, Food Surveys Research Group (Beltsville, MD) and U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics (Hyattsville, MD).
5. Mozaffarian D, Micha R, Wallace S. Effects on coronary heart disease of increasing polyunsaturated fat in place of saturated fat: a systematic review and meta-analysis of randomized controlled trials. PLoS medicine 2010;7(3):e1000252.
6. Johnson GH, Fritsche K. Effect of dietary linoleic acid on markers of inflammation in healthy persons: a systematic review of randomized controlled trials. Journal of the Academy of Nutrition and Dietetics 2012;112(7):1029-41, 41 e1-15.
Competing interests: No competing interests