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Letter to the Editor: Monounsaturated fats. Roehm E. Am J Clin Nutr 2009; 90:697-8

For critique of the paper's statistical approach- see paragraphs 4-5.

The evidence based Mediterranean diet reduces coronary heart disease risk; and plant derived monounsaturated fats may reduce coronary heart disease risk  

Dear Sir

  To the Editor:  In the May 2009 issue of American Journal of Clinical Nutrition, an article by Jacobsen et al (1) contributes to the literature by analyzing dietary fat and the associated risk of coronary disease using a pooled analysis of 11 studies. The editorial (2) accompanying this article suggests the data presented in the article “raise some concern about advice to eat a Mediterranean diet”.  The editorial also appears to suggest that advice to follow the Mediterranean diet does not represent “evidence-based medicine”.

The benefits of a Mediterranean diet are, in fact, supported by the highest level of evidence. There is a randomized trial involving cardiac patients in whom the Mediterranean diet demonstrated a significant reduction in total mortality (3).  Of note, only four valid randomized clinical trials show a significant benefit of dietary intervention on total mortality: three trials involving the intake of fish or fish derived omega-3 fats (4-6) and one randomized trial involving the Mediterranean diet (3). A randomized clinical trial demonstrating a statistically significant benefit in total mortality, rather than a benefit for a surrogate endpoint, is the pinnacle of evidence based medicine.

Supporting evidence for the benefit of the Mediterranean diet includes population studies of a number of populations with well characterized diets. The Cretan Mediterranean diet at the time of the Seven Countries Study had 31% of caloric intake from olive oil and 90% from plant based sources (7). The Mediterranean diet in each of the 5 separate populations in Greece and Italy , all of whom had fat intake predominantly based on plant sources of monounsaturated fatty acids (olive oil), was associated with low rates of coronary heart disease (CHD) (8). A subsequent study conducted in Greece followed 22,000 individuals and found that greater adherence to the traditional Mediterranean diet was associated with a significant reduction in CHD and lower total mortality (9).  Hence, the Mediterranean diet has multiple levels of evidence of benefit and is unique in being a comprehensive dietary approach for which a randomized clinical trial demonstrates a significant reduction in mortality. 

In regards to the article by Jacobsen et al (1), the authors suggest in their conclusions that replacing saturated fatty acids (SFAs) with polyunsaturated fatty acids (PUFAs), rather than monounsaturated fatty acids (MUFAs) prevents CHD.  Also, in the report, Table 2 lists information on “MUFAs for SFAs”. Similarly, the discussion section regarding the CHD risk refers to “a lower intake of SFAs and a concomitant higher energy intake from MUFAs”. However, the concept that this study gives information on MUFAs replacing SFAs appears to be a misinterpretation of the data.

In populations studied by Jacobsen et al, monounsaturated fatty acid (MUFA) intake was actually linked with saturated fatty acid (SFA) intake, rather than MUFA intake replacing SFA intake. The main source of MUFA intake in the groups analyzed by Jacobsen et al was meat and dairy products (1). Since MUFA intake in this study involved the intake of saturated fat (given that meat and dairy products were the main source of MUFA), there is not good information on MUFA replacing SFA in the report.  As an example, 200 calories of ground beef contains an approximate average of 5g of SFAs and 6g of MUFAs (USDA SR-21). The intake of that ground beef necessarily entails both SFA intake and MUFA intake. Statistical manipulation can not validly convert this to the equivalent of the replacement of SFA intake by MUFA intake.

Though every statistical technique has its strengths and weaknesses, populations where MUFA intake is predominantly the result of meat and dairy fats are unlikely to show a benefit of MUFA intake.

In a different analysis of  40 countries with population of at least one million and for which CHD mortality rates and food supply data was obtainable, CHD mortality was most strongly positively correlated to caloric intake from animal sources and most strongly negatively correlated with caloric intake from plant sources (10).  Of note, at least three of the forty countries in the study, Greece , Italy , and Spain , had substantial MUFA intake from plant sources, with each country treated as a separate data point.

Overall, MUFA intake in this analysis of 40 countries was strongly associated with SFA intake. Before adjusting for SFA and cholesterol intake, the intake of MUFA correlated to increased CHD mortality.  However, after adjusting for the cholesterol saturated fat index (CSI= 1.01 x g of saturated fat + 0.05 x mg of cholesterol), both MUFA (r= -0.33) and PUFA (r= -0.33) intake were equally and significantly negatively correlated with CHD mortality (10). 

The Seven Countries Study, on the other hand, reported on the 15 year follow up regarding diet and cumulative death rates for 15 separate populations (8). Coronary heart disease death rates were low in cohorts where olive oil supplied the predominant fat in the diet. When multiple regression analysis was performed for five variables consisting of SFA, MUFA, PUFA, protein, and alcohol, only SFA intake significantly positively correlated to a higher CHD mortality, and MUFA intake had a trend to a negative correlation with CHD mortality.

The results of these three studies may actually be consistent with one another in regards to MUFA intake. Studies of populations in which MUFA intake is predominantly on the basis of animal products, such as the analysis by Jacobsen et al, are unlikely to show a benefit of MUFA intake in regard to CHD. Studies of populations that include groups having significant intake of MUFA on the basis of plant products such as olive oil, as seen in the 40 country analysis and in the Seven Countries Study, may show a benefit for MUFA intake in regards to CHD after the findings are adjusted for saturated fat. The differing results of these studies in regards to the effect of MUFA intake on CHD is substantially influenced by the dietary patterns of the populations being evaluated.


1.  Jakobsen MU, O’Reilly EJ, Heitmann BL, et al. Major types of dietary fat and risk of coronary heart disease: a pooled analysis of 11 cohort studies. Am J Clin Nutr 2009;89:1425-32.

2.  Katan MB. Omega-6 polyunsaturated fatty acids and coronary heart disease. Am J Clin Nutr 2009;89:1283-4.

3.  Renaud S, de Lorgeril M, Delaye J, et al. Cretan Mediterranean diet for prevention of coronary heart disease. Am J Clin Nutr 1995;61(suppl):1360S-7S.

4.  Burr ML, Fehily AM, Gilbert JF, et al. Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART). Lancet 1989;ii:757-61.

5.  GISSI-Prevenzione Investigators. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Lancet 1999;354:447-55.

6.  GISSI-Prevenzione Investigators, Tavazzi L, Maggioni AP, Marchioli R, et al.  Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet 2008;372:1223-1230.

7.  Keys A, Aravanis C, Sdrin H. The diets of middle-aged men in two rural areas of Greece . Voeding 1966;27:575-86.

8.  Keys A, Menotti A, Karvonen MJ, et al. The diet and 15-year death rate in the Seven Countries Study. Am J Epidem 1986;124:903-915.

9.  Trichopoulou A, Costacou T, Bamia C, et al. Adherence to a Mediterranean Diet and Survival in a Greek Population. N Engl J Med 2003;348:2599-608.

10. Artaud-Wild SM Connor SL, Sexton G, Connor WE. Differences in coronary mortality can be explained by differences in cholesterol and saturated fat intakes in 40 countries but not in France and Finland . Circulation 1993;88:2771-79.

E Roehm, MD