Mediterranean Diet Rich in Olive Oil and Walnuts Protects Against Oxidative Dama

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Mediterranean Diet Rich in Olive Oil and Walnuts Protects Against Oxidative Damage

News Author: O'RiordanCME Author: Vega, MD

from Heartwire — a professional news service of WebMD

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 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.

Table. PREDIMED Study: Adjusted 3-Month Changes in Oxidized LDL*

Measure

Mediterranean DietSupplemented WithVirgin Olive Oil(n = 122)

Mediterranean DietSupplemented WithNuts(n = 128)

Low-Fat Diet(n = 121)

P value

Oxidized LDL, U/L

-10.6

-7.3

-2.9

..017

*Adjusted for baseline values, including sex, age, center, weight, physical activity, smoking status, diabetes, and LDL/high-density lipoprotein cholesterol ratio. LDL indicates low-density lipoprotein.Source: Arch Intern Med. 2007;167:1195-1203.

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.

The complete contents of Heartwire, a professional news service of WebMD, can be found at www.theheart.org, a Web site for cardiovascular healthcare professionals.

Clinical Context

The Mediterranean diet has previously been demonstrated to improve mortality rates. In a previous study by Knoops and colleagues of individuals between the ages of 70 and 90 years, adherence to the Mediterranean diet, moderate alcohol intake, exercise, and not smoking were each associated with a reduction in total mortality as well as mortality related to coronary heart disease, cancer, and all cardiovascular causes. The study results, which were published in the September 22, 2004, issue of JAMA, also showed that combining all 4 healthy lifestyle choices resulted in a hazard ratio of death of 0.35 compared with individuals who did not practice these behaviors.

Oxidation of lipoproteins has been implicated in the promotion of cardiovascular disease, and there have been no randomized controlled studies demonstrating that the Mediterranean diet can improve markers of oxidation. The current study by Fitό and colleagues addresses this issue.

Study Highlights

Study subjects were between the ages of 55 and 80 years and had type 2 diabetes or 3 or more other risk factors for coronary heart disease. Individuals with established cardiovascular disease or other severe chronic illness were excluded from study participation. Participants were randomized to 1 of 3 diets: low fat; Mediterranean diet with supplies of free, excess virgin olive oil; or the Mediterranean diet plus supplies of free, excess nuts. All participants underwent an evaluation at baseline that measured cardiovascular risk factors. Outcome measures included serum lipids and measures of lipid oxidation, including serum glutathione peroxidase and malondialdehyde in mononuclear cells. The main study outcome was the relationship between diet and the measures of lipid oxidation. This result was adjusted for the presence of other cardiovascular risk factors. 772 subjects underwent randomization. The mean age of participants was 67 years, and more than half of the study cohort were women. Slightly more than half of subjects had diabetes, and the mean total cholesterol level was approximately 215 mg/dL. The lipid profile was generally worse as levels of oxidized LDL rose. Serum markers indicated that diet adherence was good. Participants in the groups consuming low-fat and Mediterranean diet plus virgin olive oil had a reduced energy intake during the trial vs baseline. Levels of oxidized LDL decreased in both Mediterranean diet groups, but this reduction reached statistical significance vs the low-fat diet group only in the Mediterranean diet plus virgin olive oil cohort. Levels of malondialdehyde in monocytes were significantly reduced in both Mediterranean diet groups vs the low-fat diet group. There were no differences in the effects of the diets based on sex. Body mass index and waist circumference did not change vs baseline in any diet group, but systolic blood pressure decreased in both Mediterranean diet groups. The Mediterranean diet plus nuts diet was associated with reduced triglyceride and higher high-density lipoprotein cholesterol levels. LDL/high-density lipoprotein cholesterol ratios were reduced in both Mediterranean diet groups vs the low-fat diet cohort.

Pearls for Practice

A previous study demonstrated that the Mediterranean diet can independently reduce the risk for total mortality as well as mortality related to coronary heart disease, all cardiovascular causes, and cancer. The diet was even more effective in reducing mortality when combined with other healthy behaviors. The current study demonstrates that the Mediterranean diet can improve the degree of lipoprotein oxidation vs a low-fat diet among older patients at high risk for cardiovascular disease.

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