June 14, 2007 (Helsinki, Finland) — Results from a study presented this week have shown that a decrease in the oxidative damage to low-density lipoprotein (LDL) cholesterol is one of the protective mechanisms in which a traditional Mediterranean diet exerts a protective effect on coronary heart disease development. The study, say investigators, provides further evidence to recommend the diet — a high-fat diet because of the large amounts of monounsaturated fatty acid–rich olive oil used in Mediterranean cultures — as a useful tool against atherosclerosis development, particularly in individuals at high risk for developing coronary disease.
"Everybody has been saying, 'The Mediterranean diet is fantastic' but there is little data showing the benefits in primary prevention, and this is one of the reasons we started the study," lead investigator Dr Maria Isabel Covas (Parc de Recerca Biomèdica de Barcelona, Spain) told heartwire. "We have also heard that it's a diet rich in fruits and vegetables, and consequently rich in antioxidants, and a lot of people simply figured it would be beneficial. But nobody has tested the antioxidant effects of diet in a randomized trial. Sometimes we assume that the ecological associations are true without ever being proven."
The results of the study, from the large Prevención con Dieta Mediterránea (PREDIMED) study, were presented at the European Atherosclerosis Society 76th Congress in Helsinki, Finland, and is published in the June 11 issue of the Archives of Internal Medicine.
PREDIMED Final Results Still to Come
Olive oil, a rich source of monounsaturated fatty acids, is a main component of the Mediterranean diet, and virgin olive oil retains all the lipophilic components of the fruit and phenolic compounds with strong antioxidant and anti-inflammatory properties, said Covas. Tree nuts, which are common to the Mediterranean diet, also have a favorable fatty acid profile and are a rich source of nutrients and other bioactive compounds, such as fiber, phytosterols, folic acid, and antioxidants, which may beneficially influence the risk for CHD, she told heartwire.
Current evidence implicates oxidative damage as part of the pathophysiological changes occurring in various diseases, such as coronary heart disease, cancer, neurodegenerative disease, and also aging, but as yet, there are no randomized controlled intervention studies assessing the efficacy of the Mediterranean diet on in vivo lipoprotein oxidation, said Covas.
The PREDIMED study, a long-term, multicenter, randomized, controlled clinical trial aiming to assess the effects of the Mediterranean diet on the primary prevention of cardiovascular disease, allowed investigators to test the hypothesis that oxidized LDL might play a major role in atherosclerosis and cardiovascular disease. An estimated 9000 high-risk participants, with 5000 participants already recruited, will be assigned to 3 interventions: Mediterranean diet with virgin olive oil, Mediterranean diet with mixed nuts, or low-fat diet. The main outcome is an aggregate of cardiovascular events, including cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, with the study expected to be completed in late 2010.
As previously reported by heartwire, data at three months showed weight and body mass index (BMI) were slightly reduced in all 3 groups, with no differences between groups. Participants in the 2 Mediterranean-diet groups, however, had lower mean plasma glucose levels, lower systolic blood pressure, and lower total-cholesterol/HDL-cholesterol ratios than those in the low-fat-diet group.
Further analyzing the preliminary 3-month data from approximately 125 patients in each treatment arm, Covas and colleagues report significant reductions in the amount of oxidized LDL cholesterol among those randomized to the Mediterranean diet when compared with those who ate just a low-fat diet.
Covas told heartwire that while this study clearly showed an antioxidant effect with a diet rich in monounsaturated fatty acids, such as a diet rich in fruits and vegetables and supplemented with virgin olive oil and nuts, she said the cardioprotective effects of the Mediterranean diet are likely due to improving important cholesterol ratios, as well as the effects on blood pressure and inflammation. This study, however, confirms previous hypotheses proposing an antioxidant effect with the popular diet.
No Effect Observed With Plant Sterols or Stanol Ester
While the PREDIMED investigators were able to shed light on the antioxidant capabilities of the Mediterranean diet, researchers investigating the long-term effect of plant sterol or stanol esters on endothelial function and arterial stiffness were less successful.
Presented at the EAS meeting in Helsinki, Finland, Dr Ariënne de Jong (Maastricht University, the Netherlands) noted that plant sterol and stanol esters are often added to a wide variety of foods because of their LDL-lowering capabilities, but the effects on markers of endothelial function and arterial stiffness are less clear. Randomizing 60 statin-treated subjects to 1 of 3 treatment arms, including those supplemented with plant sterol esters, those supplemented with plant stanol esters, and those randomized as a control, investigators showed that while the plant-based supplements lowered LDL cholesterol significantly compared with controls, there were was no difference in numerous markers of endothelial function or arterial stiffness.
Speculating that these patients might have been "too healthy" to observe the benefits of the plant sterol and stanol esters, in post hoc analysis, de Jong and colleagues looked only at subjects with elevated MMP-9 levels, a marker for the presence and instability atherosclerotic plaques. In these subjects with high baseline markers of atherosclerotic burden, the plant stanol and sterol ester additives did improve arterial stiffness.
European Atherosclerosis Society 76th Congress: Workshop 1. Presented Monday, June 11, 2007.
Arch Intern Med. 2007;167:1195-1203.
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