**6. Monounsaturated fat**

Compared with clinical studies on PUFA, fewer studies focusing on MUFA have been published in the literature. Whereas the replacement of SFA in the diet with MUFA increased CV events in some studies [74], other studies showed reduction [190] or no change [56, 191] in CV events. As already described, one plausible

reason for this inconsistency is the type of MUFA in the studies. It seems clear that substitution of SFA with olive oil consistently reduced CV events, meaning that it is necessary to recognize the different metabolic effects between olive oil and other oils that contain MUFA.

In order to show the uniqueness of the intervention group in this Lyon Diet Heart study, the nutrient profiles of the NECP/AHA step 1 and step 2 are also presented. Because the intake of calories and the percentages of energy (*E*%) of three major nutrients were relatively similar, it appears that the differences in fat components had substantial effects on CV events. In the Mediterranean diet group, SFA was 32% lower (8.0 vs. 11.7%), oleic acid (MUFA) was 20% higher (12.9 vs. 10.8%), and αlinolenic acid (n-3 PUFA) was 190% higher (0.84 vs. 0.29%). Because there was no restriction of butter, fatty red meat, or snacks (rich sources of SFA) in the control diet group, and animal meat has also high content of MUFA, the energy percentage of SFA was high in the control diet group and the total unsaturated fat (MUFA + PUFA) was not different between the two groups (control vs. Mediterranean: 16.9 vs. 17.5%). The change in fat components in the Mediterranean diet group was not in accord with the current general recommendations regarding SFA and PUFA. The group had relatively high intake of SFA (8%) and lower intake of PUFA than in the control group (4.6 vs. 6.1%, **Table 4**), which could explain the small change in LDL cholesterol by the intervention. The findings in this study clearly illustrate the

Compared with data in PREDIMED study [6], conducted two decades later, which was loaded with extra-virgin olive oil and nuts with less refined carbohydrate, the percentage of energy of MUFA was almost half (12.9 vs. 22.1%), fat calorie was 10.8% lower (30.4 vs. 41.2%), and inversely, carbohydrate calories were 12.2% higher in the Mediterranean diet group in the Lyon Diet study (53.4 vs. 41.2%). Furthermore, the percent of calories from n-3 PUFA was low compared with those values in the REDUCE-IT [156] and JELIS [163] studies where highly purified marine-derived n-3 EPA was given. Therefore, it is unlikely that the beneficial, biological effects of n-3 PUFA or MUFA on CV risk reduction were maximally utilized for the reduction of CV events in the Lyon Diet Heart study. The very high value of SFA in the control group (11.7%) may be another factor contributing the exaggerated CV event reduction in this study. In one cohort study with 2.96 million person-years of follow-up which evaluated effects of red meat consumption on risk of CV diseases [197], the total mortality in the top quintile was 40% higher than in the bottom quintile. SFA consumption in the control group in the Lyon Diet Heart study was almost identical to that in the top quintile in that cohort study. At present, as SFA is well known to increase in LDL cholesterol, it is nearly impossible to conduct any diet trials with more than 8% intake of SFA for ethical reasons.

The second RCT of the Mediterranean diet was the PREDIMED study [6]. There are several distinctions between the Lyon Diet Heart and PREDIMED studies. First, the PREDIMED study had much more participants (605 vs. 7447 subjects). Second, the Lyon Diet Heart study enrolled subjects with a history of acute myocardial infarction, and by contrast, the target is primary prevention with a high CVD risk in the PREDIMED study. Third, the Mediterranean diets were substantially different in the two studies. In the Lyon Diet Heart study, the Mediterranean diet was enriched with alpha-linolenic acid (n-3 PUFA), because margarine was provided freely in substitution for butter and cream, but not olive oil, and, by contrast, in the PREDIMED study, the diet for participants assigned to be the Mediterranean groups was loaded with extra-virgin olive oil or nuts. Finally, regarding the fat content in the control group diet, a high-fat diet was used in the Lyon Diet Heart and a low-fat

importance of the risk factors beyond lipids and lipoproteins.

*Effects and Issues of Diet Fat on Cardiovascular Metabolism*

*DOI: http://dx.doi.org/10.5772/intechopen.93261*

**6.3 PREDIMED study**

**6.4 Protocol and results**

diet in the PREDIMED study.

**95**
