Mediterranean Diet Study- PrediMed Trial
reviewed by E.Roehm, M.D. 2013
The Short Take- New Trial released Feb. 2013:
The PrediMed trial is an important randomized trial showing that an increase in extra virgin olive oil and nut intake within the context of a Mediterranean diet is beneficial. This study was performed in Spain with over 7,000 participants and showed a significant (28-30%) reduction in the combined endpoint of heart attack, stroke and cardiovascular death. This trial demonstrated a significant reduction (≈39%) in stroke as an isolated endpoint. The trends for improvement in regards to heart attack and total mortality were not statistically significant.
The trial was a primary prevention trial with enrollment limited to individuals who were at risk for developing future heart attacks and strokes but without any prior history of cardiovascular problems. Participants were randomized to one of 3 groups: a Mediterranean diet with supplemental extra virgin olive oil, a Mediterranean diet with supplemental nut intake, and a control diet which received low fat instruction, though with very little reduction in actual fat intake. Median follow-up of trial participants was 4.8 years. This trial shows benefits occurring in patients without prior heart disease which expands on the Lyon Diet Heart Trial results which showed a reduction in heart attack as well as a reduction in total mortality with a Mediterranean diet for individuals with a prior heart attack (secondary prevention).
(See Mediterranean diet video for foods making up this diet and strongest evidence of benefit.)
The Long Take– New Trial Result released Feb. 2013:
The PrediMed (Prevencion con Dieta Mediterranea) study1 is a major randomized trial showing that an increase in extra virgin olive oil and nut intake in the context of a Mediterranean diet results in fewer adverse cardiovascular events (combined endpoint of heart attack, stroke, and cardiovascular death).
The study was performed in Spain and published online February 2013 in the New England Journal of Medicine. The trial participants had no prior history of cardiovascular disease before trial enrollment, but were all required to have significant cardiovascular risk factors present to be eligible.
A total of 7,447 persons in Spain were randomized to either a Mediterranean diet with increased extra virgin olive oil, a Mediterranean diet with increased nut intake, or a control diet where the participants received low fat diet advice. The high extra virgin olive oil group ingested an average of 3.6 tablespoons/day (51 grams/day equal to 459 calories/day) of olive oil with 98% of it being extra virgin olive oil. The high nut group ate 8.2% of their total daily calories in the form of nuts, including an additional approximately one ounce packet of nuts (15g of walnuts, 7.5 g of almonds, and 7.5g of hazelnuts) provided by the study coordinators.
Participants at time of entry to the trial did not have preexisting cardiovascular disease (stroke, heart attack) but were at risk for cardiovascular disease in the future. All participants were required to have either type 2 diabetes, or at least three of the following risk factors: smoking, hypertension, elevated “bad” cholesterol (LDL), low “good” cholesterol (HDL), be substantially overweight, or have a family history of premature heart disease.
This large multi-center trial showed that a higher intake of extra virgin olive oil as well as a higher intake of nuts resulted in statistically significant 28-30% reduction in total cardiovascular events (combined endpoint of heart attack, stroke, and cardiovascular death). At the end of the trial, 3.8% of Mediterranean with olive oil group had a cardiovascular event, 3.4% of the Mediterranean with nut group, and 4.4% of the control group. There was a statistically significant reduction in stroke rate (≈39%) when considered as an isolated endpoint. The trends for improvement in regards to heart attack and total mortality were not statistically significant. Hence, the trial shows evidence for a statistically significant reduction for the combined cardiovascular endpoint as well as a reduction for stroke as a solitary endpoint.
In regards to the dietary changes achieved in the three study groups, the major change in the Mediterranean diet group with the extra virgin olive oil (Med-EVOO) group was a substantial increase in the intake of extra virgin olive oil. This resulted during the trial of an intake of 50 g/day of extra virgin olive oil in the Med-EVOO group vs. 23 g/day of extra virgin olive oil in the control group. In the Mediterranean Nut (Med-Nut) group there was over a 200% increase in nut intake. Nuts comprised 8.2% of the caloric intake in the Med-Nut group vs. 1.6% of the caloric intake in the control group.
This study is not a Mediterranean diet vs. a low fat diet. The control group received low fat diet advice, though the authors do not say the control group followed a low fat diet. (End of trial fat intake as a percentage of total cal: Med-EVOO 41%, Med-Nut 39%, Control Diet- 37%.).
There were multiple other statistically significant changes in different types of food intake other than olive oil and nuts (legumes, fish, etc.), but the magnitude of these changes was small in relation to the total daily intake of each food type. As an example, at baseline prior to the trial, participants in all three groups averaged slightly less than one serving of fish or seafood daily. As part of the study, both the Mediterranean diet olive oil (Med-EVOO) group and the Mediterranean diet nut (Med-Nut) group received instruction to increase fatty fish intake, while the control group was advised to decrease fatty fish intake. Subsequently, during the trial, the intake of fish (marine) omega-3 fatty acids* in grams/day increased from 0.8 to 0.9 g/day in the Med-EVOO group, remained unchanged at 0.8 g/day in the Med-Nut group, and decreased from 0.8 to 0.7 g/day in the control diet. Hence, though other dietary changes occurred, the increased olive oil intake and increased nut intake are the most prominent changes between the diet intervention groups and the control diet. Given that the study took place in Spain, the average participant’s baseline diet had many features of the typical Mediterranean diet. Even after the intervention the intake of most of the various food components was similar for all three groups.
The authors of the study correctly stated, “The interventions were intended to improve the overall dietary pattern, but the major between group differences involved the supplemental items (extra virgin olive oil and nuts). Thus, extra virgin olive oil and nuts were probably responsible for most of the observed benefits of the Mediterranean diet.”
This important diet study shows that extra virgin olive oil, as well as increased tree nuts in the context of a Mediterranean diet resulted in a reduction in stroke for individuals at high risk for cardiovascular disease but without preexisting disease.
These trial results add important additional randomized trial data to the benefits already proven for the Mediterranean diet by the Lyon Diet Heart Study. The Lyon Diet Heart Study2 results showed that a Mediterranean diet resulted in fewer cardiovascular events (73% reduction) as well as a statistically significant lower total death rate (>50% reduction) for participants who were randomized to either a Mediterranean diet or a control diet within 6 months of having a heart attack. There were substantial differences in the intake of multiple food groups that constitute the Mediterranean diet between the Mediterranean diet group and the control group in the Lyon Diet Heart Trial.
Hence, the Mediterranean diet and some of its dietary components have been proven to be beneficial by randomized trials. There have been few, if any, other comprehensive dietary approaches that have been proven to have statistically significant differences in heart attack, stroke, and cardiovascular death. There are no other comprehensive dietary approaches that have shown a reduction in total mortality.
The PrediMed trial of extra virgin olive oil and increased nut intake represents a very important addition to information about the effects of the dietary components of the Mediterranean diet on stroke as well as on the combined cardiovascular endpoint of stroke, cardiovascular death, and heart attack.
These trial results add important additional randomized trial data to the Lyon Diet Heart Study supporting the benefits of a Mediterranean diet.
References:
- Estruch R, Ros E, Salas-Salvadó J, Martínez-González MA, et al. for the PREDIMED Study Investigators. Primary Prevention of Cardiovascular Disease with a Mediterranean Diet. On line publication NEJM:February 25, 2013DOI: 10.1056/NEJMoa1200303
- de Lorgeril M, Renaud S, Mamelle N, Salen P, Martin JL, Monjaud I, Guidollet J, Touboul P, Delaye J. Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease. Lancet. 1994;343:1454-9.
* “fish” omega-3 fatty acids, marine omega-3 fatty acids, and marine n-3 fatty acids are all equivalent terms
