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5 Studies on The Mediterranean Diet – Does it Really Work?

Greek Woman With Strawberries on Her HeadBack in the early 20th century, heart disease had become a huge problem.

At that time, researchers studying the cause of heart disease noted a striking pattern…

The people in certain countries around the Mediterranean sea (like Italy and Greece) had very little heart disease compared to Americans.

The researchers believed that the reason for their low heart disease rates was their healthy diet.

This diet was high in plants, including fruits, vegetables, whole grains, breads, legumes, potatoes, nuts and seeds.

They also used hefty amounts of both extra virgin olive oil and red wine, along with moderate amounts of fish, poultry, dairy and eggs. Red meat was eaten only rarely.

Although this type of diet has been consumed for a long time around the Mediterranean, it only recently gained mainstream popularity as a good way to improve health and prevent disease.

Since then, numerous studies have been conducted on this diet, including several randomized controlled trials… which are the gold standard in science.

This article takes an objective look at 5 long-term controlled trials on the Mediterranean Diet. All of them are published in respected, peer-reviewed journals.

The Studies

Most of the participants are people who already have health problems such as diabetes and metabolic syndrome, or are at a high risk of heart disease.

The majority of the studies looked at common health markers like weight, heart disease risk factors and markers of diabetes. The larger and longer-term studies also looked at hard end points like heart attacks and death.

1. The PREDIMED Study

The PREDIMED study made headlines in 2013 for having caused a substantial reduction in cardiovascular disease.

This was a large study, with a total of 7447 individuals who were at a high risk of cardiovascular disease. They were randomized to three different diets:

  • A Mediterranean Diet with added extra virgin olive oil (Med + Olive Oil).
  • A Mediterranean Diet with added nuts (Med + Nuts).
  • A low-fat control group.

No one was instructed to reduce calories or increase physical activity. This study went on for almost 5 years and many papers have been written about it, some of them looking at different risk factors and end points.

Here are 6 papers (1.1 to 1.6) from the PREDIMED study.


1.1 Estruch R, et al. Primary Prevention of Cardiovascular Disease with a Mediterranean Diet. The New England Journal of Medicine, 2013.

Details: 7447 individuals at a high cardiovascular risk were randomized to a Mediterranean diet with added olive oil, a Mediterranean diet with added nuts, or a low-fat control group. The study went on for 4.8 years.

In this paper, researchers primarily looked at the pooled risk of heart attack, stroke and death from cardiovascular causes.

Results: The risk of of combined heart attack, stroke and death from cardiovascular disease was reduced by 30% in the Med + Olive Oil group, and 28% in the Med + Nuts group.

Ramon et al, 2013

Some more details:

  • The results were only significant in men, not women.
  • The risk of stroke went down by 39% in the Mediterranean diet groups.
  • There was no statistically significant difference in heart attacks.
  • Dropout rates were twice as high in the control group (11.3%), compared to the Mediterranean diet groups (4.9%).
  • When looking at subgroups, people with high blood pressure, lipid problems or obesity responded best to the Mediterranean diet.
  • Despite this study being hailed as a success story, there was no statistically significant difference in total mortality (risk of death).

Conclusion: A mediterranean diet with either olive oil or nuts may reduce the combined risk of stroke, heart attack and death from cardiovascular disease. There was no statistically significant effect in women and no reduction in mortality.


1.2 Salas-Salvado J, et al. Effect of a Mediterranean Diet Supplemented With Nuts on Metabolic Syndrome Status. JAMA Internal Medicine, 2008.

Details: Data from 1224 individuals in the PREDIMED study was analyzed after 1 year, examining whether the diet helped individuals reverse the metabolic syndrome.

Results: The prevalence of metabolic syndrome decreased by 6.7% in the Med + Olive Oil group and 13.7% in the Med + Nuts group. The results were statistically significant only for the Med + Nuts group.

SS Jordi, 2008

Conclusion: A mediterranean diet supplemented with nuts may help to reverse the metabolic syndrome.


1.3 Montserrat F, et al. Effect of a Traditional Mediterranean Diet on Lipoprotein Oxidation. JAMA Internal Medicine, 2007.

Details: 372 individuals from the PREDIMED study who were at a high cardiovascular risk were assessed after 3 months, looking at changes in oxidative stress markers like oxidized LDL (ox-LDL).

Results: The levels of oxidized LDL decreased in both Mediterranean Diet groups, but did not reach statistical significance in the low-fat control group.

LDL Oxidized Levels

Conclusion: The mediterranean diet caused reductions in oxidized LDL cholesterol, along with improvements in several other heart disease risk factors.


1.4 Salas-Salvado J, et al. Reduction in the Incidence of Type 2 Diabetes With the Mediterranean Diet: Results of the PREDIMED-Reus nutrition intervention randomized trial. Diabetes Care, 2011.

Details: 418 non-diabetic participants in the PREDIMED study were assessed after 4 years, looking at their risk of having developed type 2 diabetes.

Results: 10 and 11% of the individuals in the Mediterranean diet groups became diabetic, compared to 17.9% in the low-fat control group. The Mediterranean diet reduced the risk of developing type 2 diabetes by 52%.

SS Jordi et al, 2011

Conclusion: A Mediterranean diet without calorie restriction appears to be effective in preventing the development of type 2 diabetes.


1.5 Estruch R, et al. Effects of a Mediterranean-Style Diet on Cardiovascular Risk Factors. Annals of Internal medicine, 2006.

Details: 772 participants in the PREDIMED study were analyzed with regards to cardiovascular risk factors, after a study period of 3 months.

Results: The Mediterranean diet caused improvements in various cardiovascular risk factors, including blood sugar levels, blood pressure, Total:HDL Cholesterol Ratio, and C-Reactive Protein (CRP).

Ramon et al 2006

Some more details:

  • Blood Sugar: Went down by 0.30-0.39 mmol/L in the Mediterranean diet groups.
  • Systolic Blood Pressure: Went down by 5.9 and 7.1 mmHG in the Mediterranean diet groups.
  • Total:HDL Ratio: Went down by 0.38 and 0.26 in the Mediterranean diet groups, compared to the low-fat group.
  • C-reactive protein: Went down by 0.54 mg/L in the Med + Olive Oil group, but did not change in the other groups.

Conclusion: Compared to a low-fat control group, a Mediterranean diet can have beneficial effects on various risk factors for cardiovascular disease.


1.6 Ferre GM, et al. Frequency of nut consumption and mortality risk in the PREDIMED nutrition intervention trial. BMC Medicine, 2013.

Details: 7216 participants in the PREDIMED study were evaluated after 5 years.

Results: After 5 years, a total of 323 people had died, with 81 cardiovascular deaths and 130 cancer deaths. Consuming nuts was linked to a 16-63% lower risk of death during the study period.

Ferré GM et al 2013

Conclusion: Consuming nuts was associated with a significantly reduced risk of death over a period of 5 years.


2. De Lorgeril M, et al. Mediterranean Diet, Traditional Risk Factors, and the Rate of Cardiovascular Complications After Myocardial Infarction: Final Report of the Lyon Diet Heart Study. Circulation, 1999.

Details: This study enrolled 605 middle-aged men and women who had suffered a heart attack.

They were split into two groups, a Mediterranean-type diet (supplemented with an Omega-3 rich margarine) and a “prudent” Western-type diet, and followed for 4 years.

Results: After 4 years, the group eating the Mediterranean diet was 72% less likely to have gotten a heart attack, or died from heart disease.

Lorgeril et al, 1999

Conclusion: A mediterranean diet supplemented with Omega-3s may be effective at preventing heart attacks in people who have already had heart attacks (secondary prevention).


3. Esposito K, et al. Effect of a Mediterranean-Style Diet on Endothelial Dysfunction and Markers of Vascular Inflammation in the Metabolic Syndrome. The Journal of the American Medical Association, 2004.

Details: 180 patients with metabolic syndrome were randomized to follow either a Mediterranean diet or a “prudent” low-fat diet for 2.5 years.

Results: At the end of the study, 44% of patients in the Mediterranean diet group still had metabolic syndrome, compared to 86% in the control group. The Mediterranean diet group also had improvements in several risk factors.

Katherine E et al,2004

Some more details:

  • Weight loss: Body weight decreased by 4.0 kg (8.8 lbs) in the Mediterranean diet group, compared to 1.2 kg (2.6 lbs) in the low-fat control group.
  • Endothelial function score: Improved in the Mediterranean diet group, but remained stable in the low-fat control group.
  • Other markers: Inflammatory markers (hs-CRP, IL-6, IL-7 and IL-18) and insulin resistance decreased significantly in the Mediterranean diet group.

Conclusion: A Mediterranean diet appears to be effective in reducing metabolic syndrome and other cardiovascular risk factor.


4. Shai I, et al. Weight Loss with a Low-Carbohydrate, Mediterranean, or Low-Fat Diet. The New England Journal of Medicine, 2008.

Details: 322 obese individuals were randomly assigned to a calorie restricted low-fat diet, a calorie restricted Mediterranean diet, or an unrestricted low-carb diet.

Results: The low-fat group lost 2.9 kg (6.4 lbs), the low-carb group lost 4.7 kg (10.3 lbs) and the Mediterranean diet group lost 4.4 kg (9.7 lbs).

Diabetic participants had improved blood glucose and insulin levels on the Mediterranean diet, compared to the low-fat diet.

Shai, et al. 2008.

Conclusion: A Mediterranean diet may be more effective for weight loss and improving symptoms of diabetes, when compared to a low-fat diet.


5. Esposito K, et al. Effects of a Mediterranean-Style Diet on the Need for Antihyperglycemic Drug Therapy in Patients With Newly Diagnosed Type 2 Diabetes. Annals of Internal Medicine, 2009.

Details: 215 overweight people who had recently been diagnosed with type 2 diabetes were randomly assigned to a low-carb Mediterranean diet, or a low-fat diet. This study went on for 4 years.

Results: After 4 years, 44% of the Mediterranean diet group and 70% of the low-fat diet group had needed treatment with medication.

The Mediterranean diet group had more favorable changes in glycemic control and heart disease risk factors.

Katherine et al, 2009

Conclusion: A low-carb Mediterranean diet may delay or prevent the need for drug therapy in patients with newly diagnosed type 2 diabetes.

Controlled Trials That Were Not Included

Two controlled trials (I, II) were not included because they were small and short in duration compared to the other 5 studies.

Risk of Death (Mortality)

Two of the studies, the PREDIMED study and the Lyon Diet Heart study, were both large enough and long enough to get results about mortality, or the risk of death during the study period (1.1 and 2).

In order to make the comparison easier, I combined the two Mediterranean diet arms of the PREDIMED study (Olive oil vs Nuts) into one.

Mediterranean Diet and Mortality

In the Lyon Diet Heart Study, the Mediterranean diet group was 45% less likely to die over the 4 year period (compared to the low-fat group). This study is often hailed as the most successful diet intervention trial in history.

The Mediterranean diet group in the PREDIMED study was 9.4% less likely to die, but the difference was not statistically significant.

Risk of Death From Cardiovascular Disease (Heart Attacks and Strokes)

Both the PREDIMED and Lyon Diet Heart Study (1.1 and 2) looked at mortality from heart attacks and strokes.

Mediterranean Diet and Cardiovascular Mortality

As you can see, the risk of dying from cardiovascular disease was reduced by 16% in the PREDIMED study (not statistically significant) and 70% in the Lyon Diet Heart Study.

The risk of stroke was reduced by 39% in the PREDIMED study (31% with olive oil and 47% with nuts), which was statistically significant. In the Lyon Diet Heart Study, 4 people in the low-fat group had a stroke, compared to 0 in the Mediterranean diet group.

Weight Loss

The Mediterranean diet is usually not prescribed as a weight loss diet, it is rather seen as a healthy diet that can help prevent cardiovascular disease and premature death.

That being said, people usually tend to lose some weight on the Mediterranean diet.

Three of the papers reported weight loss numbers (3, 4, 5):

Mediterranean Diet and Weight Loss

In every study, the Mediterranean group lost more weight than the low-fat group, but it was only statistically significant in one of the studies (3).

Metabolic Syndrome and Type 2 Diabetes

Several of these studies showed that the Mediterranean diet can have benefits for people with metabolic syndrome and type 2 diabetes.

  • The PREDIMED study (1.2) showed that a Mediterranean diet with nuts helped 13.7% of patients with metabolic syndrome reverse their condition.
  • Another paper from the same study (1.4) showed that the Mediterranean diet reduced the risk of developing type 2 diabetes by 52%.
  • Esposito, 2004 (3) showed that the diet helped reduce insulin resistance, one feature of metabolic syndrome and type 2 diabetes.
  • The Shai study (4) showed that the Mediterranean diet improved blood glucose and insulin levels compared to the low-fat diet.
  • Esposito, 2009 (5) showed that the diet could delay or prevent the need for drugs in patients with newly diagnosed type 2 diabetes.

It seems pretty clear that the Mediterranean diet is a much better option for type 2 diabetic patients than a low-fat diet.

Number of People Who Dropped Out of The Studies

All studies reported dropout rates. That is, the percentage of people who abandoned the study.

Mediterranean Diet and Dropout

No clear patterns emerged in the dropout rates between the Mediterranean and the low-fat diet.

Take Home Message

It seems clear from looking at the evidence that the Mediterranean diet is very healthy and may help prevent some of the world’s leading killers.

It is obviously a much better option than the standard low-fat diet that is still being recommended all around the world.