Life Extension Magazine®

Newly Discovered Longevity Benefits of Mediterranean Diet

New England Journal of Medicine reports that the Mediterranean diet reduces cardiovascular events, including death, by 30%. Plant polyphenols are identified as the main contributor for these heart-health benefits.

Scientifically reviewed by: Dr. April Parks, MD, MS, in August 2023. Written by: Michael Campbell.


A study published in the New England Journal of Medicine showed that following a Mediterranean diet contributed to a 30% reduction in the combined risk of acute heart attack, stroke, or cardiovascular death.1

This study further validates that a Mediterranean diet is an effective health intervention capable of significantly lowering cardiovascular disease risk.

While it is now clear that following a Mediterranean diet leads to cardiovascular benefits, researchers continue to examine how the diet provides such strong protection.

New studies reveal that the high content of polyphenols found in the foods that comprise the Mediterranean diet is a key factor in its ability to reduce the risk of dying.2-4

The beneficial impact of a healthy diet on human physiology remains grossly underappreciated.

Virtually every degenerative disease can be favorably influenced by dietary intervention. Yet modern medicine relies almost exclusively on prescription drugs to treat chronic illnesses.

The challenge is that many people feel “addicted” to food groups that are highly toxic. The good news is that following a lifesaving Mediterranean diet does not require deprivation of delicious foods, and the healthy polyphenols can be obtained in dietary supplements.

In a recent study presented at the European Society of Cardiology Congress 2016, researchers looked at survival rates of cardiovascular disease patients who followed a Mediterranean-style diet.

The study tracked 1,197 people over seven years. It found that those who most closely followed a Mediterranean diet died 37% less often than those with the least compliance with the diet.5

A separate analysis of 92 studies involving about 200,000 people found that statin (cholesterol-lowering) drugs reduce the risk of death by 18% in those with cardiovascular disease.6

Although these are not directly comparable studies, they nevertheless suggest that a healthier diet is more effective in keeping those with pre-existing cardiovascular disease alive.

These findings were presented at the world’s largest conference on cardiovascular disease. Scientists at this conference hailed the new findings as “extraordinary,” showing that adhering to a Mediterranean diet is “more powerful than any drug.7

This is not the first report showing reductions in mortality in those who follow a Mediterranean-style diet. Food/drinks that comprise this diet provide plant polyphenols along with olive oil and omega-3s, all of which have been shown to confer longevity.

Another feature of a Mediterranean-style diet is that it doesn’t involve heavy meat eating. A growing body of data implicates heavy meat eating with a host of degenerative illnesses such as Alzheimer’s dementia. Reducing meat consumption could significantly reduce the risk of AD as well as of several cancers, diabetes mellitus type 2, stroke, and, likely, chronic kidney disease.8


Proving Cardiovascular Benefits of Mediterranean Diet

Proving Cardiovascular Benefits of Mediterranean Diet  

A study published in the New England Journal of Medicine utilized the preferential full, randomized, controlled study design.1

Called PREDIMED (PREvención con DIeta MEDiterránea), the study involved 7,447 women (aged 60 to 80) and men (aged 55 to 80) who were at a high cardiovascular risk but did not have cardiovascular disease when they enrolled in the study.

Subjects were randomly assigned to one of three groups:

  • Mediterranean diet plus 4 tablespoons of extra virgin olive oil daily
  • Mediterranean diet plus one ounce of nuts daily
  • Control diet

By the end of the study, both Mediterranean diet groups experienced a significant 30% reduction in the combined risk of acute heart attack, stroke, or cardiovascular death over the five-year period, compared with the control group.

What is compelling about these findings is that the people in the Mediterranean diet groups had fewer dietary restrictions compared with the control group, and none of the groups restricted their caloric intake or boosted their exercise at all. (See Table 1 on page 29 for more foods contained in Mediterranean-style diets.)

More importantly, this study validated the Mediterranean diet as a true health intervention that can significantly lower cardiovascular disease risk.

This is a radical advance over many previous studies, which could only show correlation between diet and heart disease risk.

What You Need to Know
Mediterranean Diet Reduces Heart Disease Risk

Mediterranean Diet Reduces Heart Disease Risk

  • Epidemiologic studies have long suggested that those who consume a Mediterranean diet have lower risks for cardiovascular disease and death.
  • A large European study called PREDIMED has now demonstrated that the Mediterranean diet, when used as a true health intervention, reduces cardiovascular disease and death risks by 30% compared with a standard low-fat diet.
  • Related studies show that polyphenol consumption is a major factor in reducing cardiovascular risk, and that the polyphenols in the Mediterranean diet directly produce reductions in cardiovascular risk factors.
  • Supplementing with polyphenols helps ensure we are getting adequate amounts of these important nutrients.

Why the Mediterranean Diet is so Beneficial

While this study demonstrated the benefits of the diet itself, it did not evaluate how it conferred this protection.

The researchers believe, however, it was likely due to the high amounts of polyphenols found in the typical Mediterranean diet. Based on calculations from Phenol-Explorer, a comprehensive database on polyphenol content in foods, the diet used in the study delivered an approximate 1,500 mg of total combined polyphenols daily.9

Plant polyphenols are complex biological molecules produced by natural processes. More than 8,000 different polyphenol compounds have been identified in plants, with several hundred readily available in edible plants.2

While best known for their ability to fight and protect against oxidative stress, polyphenols have numerous other properties. These include anti-inflammatory, anticarcinogenic, antidiabetic, antiobesity, and anti-allergic properties, along with liver and stomach protective effects.2

Epidemiological studies compellingly demonstrate the clinical impact of these mechanisms in preventing cardiovascular and neurodegenerative diseases, as well as certain cancers.2,10-20

In order to determine if polyphenols were in fact the reason for the dramatic risk reductions in cardiovascular disease and death in those following a Mediterranean diet, the researchers conducted two sub-studies as part of the original PREDIMED randomized controlled trial. Each study evaluated the connection between polyphenols and a risk factor for cardiovascular disease.

Let’s examine each study.

Polyphenols Reduce Blood Pressure

The first study evaluated a subgroup of 200 people from the PREDIMED study.3 The researchers examined the impact of the two Mediterranean diets (one with extra virgin olive oil and one with nuts) on blood pressure at the start of the study, and after just one year of being on the diet.

Their goal was to determine if there was a connection between polyphenol levels and blood pressure.

They found that those patients on either of the two Mediterranean diets experienced significant reductions in both diastolic and systolic blood pressure compared with those on the control or non-Mediterranean diet.

What’s more, these blood pressure reductions were associated with significant increases in total urinary polyphenols as well as plasma nitric oxide (NO) levels.3 Endothelial nitric oxide is the body’s natural blood-vessel relaxant, and is a biomarker of good cardiovascular function and healthy aging.21

This study gives us our first clue as to how the polyphenols in the Mediterranean diet promote healthy aging and protection against cardiovascular disease: by directly improving vascular function and reducing blood pressure.

An additional follow-up study provides insight into another key mechanism of action.

Polyphenols Reduce Inflammation

To learn more, researchers followed a subset of 1,139 subjects in the PREDIMED study in order to determine if polyphenol levels were connected with inflammatory markers.4

Chronic inflammation is a recognized fundamental contributor to cardiovascular disease, and polyphenols are known anti-inflammatory agents, so this was a sensible area of investigation.

At the end of one year, subjects with the greatest increases in urinary polyphenols had significantly lower levels of five important markers of inflammation that correlate with cardiovascular risk. These include:

  • Vascular cell adhesion molecule-1 (VCAM-1),
  • Intercellular adhesion molecule-1 (ICAM-1),
  • Interleukin-6 (IL-6),
  • Tumor necrosis factor alpha (TNF-alpha), and
  • Monocyte chemotactic protein-1 (MCP-1).

In addition, subjects with the greatest rise in polyphenol levels had significantly lower systolic and diastolic blood pressure, and significantly increased levels of beneficial HDL cholesterol, compared with those with the lowest polyphenol elevations.

It is clear from these studies that the polyphenols in the Mediterranean diet account for a large proportion of its value in preventing catastrophic heart disease, stroke, and cardiovascular deaths.

Mediterranean Diet Reduces Brain Shrinkage
Mediterranean Diet Reduces Brain Shrinkage

It’s a sad fact of biology that our brains shrink as we age. But a new study published in the journal Neurology has shown that those who followed the Mediterranean diet—primarily composed of fruits, vegetables, beans, olive oil and moderate amounts of fish and red wine—experienced reduced brain shrinkage.50 This finding implies longer enhanced cognitive health and adds a new item to the long list of health benefits achieved by those who follow the diet.

Researchers from Scotland’s University of Edinburgh, led by Michelle Luciano, PhD, investigated the effects of the Mediterranean diet on brain volume. They found that subjects who stuck the closest to the diet had just half the brain shrinkage suffered by their less diet-faithful counterparts over the course of the three-year study.

“As we age, the brain shrinks and we lose brain cells, which can affect learning and memory,” remarked Dr. Luciano. “This study adds to the body of evidence that suggests the Mediterranean diet has a positive impact on brain health.”51

Remarkably, the diet-faithful subjects, ages 73 to 76, gained the cognitive benefits regardless of their original level of intellect or education.

The study didn’t find that greater fish consumption vs. lesser meat consumption correlated with reduced brain shrinkage, as has been suggested by some past research. Rather, the authors are in agreement with many other researchers who suggest it’s specifically the plant-based foods which make up the majority of the Mediterranean diet that are collectively responsible for the improved brain health.

Polyphenols Reduce Risk of Dying

One of the most compelling studies on polyphenols was one published in the Journal of Nutrition showing that polyphenol intake reduces the overall risk of dying.

This study examined the natural intakes of polyphenols in 807 men and women aged 65 years and older using a measurement of total urinary polyphenols.2 The subjects provided 24-hour urine specimens at baseline, and were then followed up for 12 years.

By the end of the study, it was clear that those who had begun the trial with the highest total urinary polyphenols (indicating the highest actual circulating levels of polyphenols in the blood) had lower all-cause mortality, compared with those with the lowest levels.

A. Mediterranean Diet – 37% lower mortality
Recommended Foods Goal for Consumption
Olive Oil At least 4 tbsp./day*
Tree nuts and peanuts At least 3 servings/week
Fresh Fruits At least 3 servings/day
Vegetables At least 2 servings/day
Fish (especially fatty fish) and seafood At least 3 servings/week
Legumes (beans) At least 3 servings/week
White meat Instead of red meat
Wine with meals (optional) At least seven glasses/week
Foods to Be Discouraged Goal for Restriction
Soda drinks Less than one/day
Commercial baked goods, sweets, pastries Less than 3 servings/week
Spreadable fats (butter, etc.) Less than one serving/day
Red and Processed meats Less than one serving/day
B. Control Low-Fat Diet – Inferior to Mediterranean Diet
Recommended Foods Goal for Consumption
Low-fat dairy products At least 3 servings/day
Bread, potatoes, rice, pasta At least 3 servings/day
Fresh Fruits At least 3 servings/day
Vegetables At least 2 servings/day
Lean fish and seafood At least 3 servings/week
Foods to Be Discouraged Goal for Restriction
Vegetable oils Not more than 2 tbsp./day
Commercial baked goods, sweets, pastries Not more than one serving/week
Nuts and fried snacks Not more than one serving/week
Red and Processed meats Not more than one serving/week
Visible fat in meats and soups Always remove
Fatty fish, seafood canned in oil Not more than one serving/week
Spreadable fats (butter, etc.) Not more than one serving/week

A) Mediterranean diet with added nuts or olive oil.
B) Control, low-fat diet based on standard dietary guidelines. Note the greater restrictions of the control diet, and the more liberal parameters of the Mediterranean Diet.

*Olive oil polyphenols can be obtained in supplements for those who don’t want to eat this much extra-virgin olive oil.

Intriguingly, this worked out to an overall 30% reduction in the risk of dying for those in the highest third of urinary polyphenols compared with those in the lowest third.

This study demonstrates that higher overall polyphenol intake is associated with a significantly lower risk of dying.

Most Important Mediterranean Polyphenols
Most Important Mediterranean Polyphenols

The studies described here clearly show the many benefits of consuming polyphenols as part of a typical Mediterranean diet.

The problem is that many of us find it difficult to adhere closely enough to the Mediterranean diet to get an optimal array of these essential plant compounds.

For example, a report from the Centers for Disease Control and Prevention (CDC) shows that Americans are not meeting their intake of fruits and vegetables.22

According to this report, during 2007-2010, 87% of Americans did not meet vegetable intake recommendations and 76% did not meet fruit intake recommendations.

In addition to these, other components of a Mediterranean diet (i.e., nuts and beans) are also known to be below the recommended intake by the American population,23,24 making supplementation with polyphenols especially critical.

Many studies have now been published on the relationship between polyphenols common in the Mediterranean diet and cardiovascular protection.3,4,25-28 These studies show a wide range of effects, depending on the specific food studied, and on the particular spectrum of polyphenols it contains.

Here is a brief summary of the polyphenols from each of the main foods found in typical Mediterranean diets, along with how they beneficially impact cardiovascular health.

Artichoke Extracts

Artichokes are a staple of the Mediterranean diet. Artichoke extracts (made from the leaf, stem, and root of artichokes) have been found to have numerous cardioprotective effects. For example, they have been shown to inhibit cholesterol synthesis and LDL oxidation.29,30

Grape Seed Extract

Grape seed extracts are loaded with polyphenols, and numerous studies have testified to their ability to protect heart health on multiple levels.

For example, grape seed extracts reduce levels of oxidized low-density lipoprotein (OxLDL) cholesterol, which is one of the earliest triggers of atherosclerosis. They also prevent oxidized LDL from binding to its receptor on endothelial cells, a highly vascular-protective effect.31,32

Other studies have shown their ability to prevent the death of cardiac muscle cells,33 activate eNOS (the enzyme responsible for producing nitric oxide),34,35 and prevent the development of low-grade inflammation by inhibiting production of inflammatory signaling molecules (cytokines). This is significant since low-grade inflammation contributes to atherosclerosis and cardiovascular risk.

Lentil Polyphenol Extract

Lentils comprise a large part of the Mediterranean diet and are a good source of fiber, B vitamins—and, of course, polyphenols. Extracts made from lentils have been found to prevent high blood pressure induced by the hormone angiotensin-II, a vessel-constricting signaling molecule. This action helps protect against arterial narrowing.37

Olive Leaf Extract

Olives are perhaps one of the most central components of the typical Mediterranean diet. Polyphenol extracts from the olive leaf have been shown to potently protect cultured heart muscle cells from destruction caused by an intense oxidant chemical challenge.38 They also decrease tissue damage by such oxidative stress, while boosting intracellular resistance systems.39

In a rat model of metabolic syndrome, these extracts were shown to improve or normalize abdominal and liver fat accumulation, excessive collagen deposition in the heart and liver, cardiac stiffness, poor glucose tolerance, and abnormal lipid profiles.40


Pecans have been associated with reductions in cardiovascular disease risk. This is in part because they play an important role in reducing LDL cholesterol.41 Research also shows that they boost plasma antioxidant capacity in the critical after-meal period, which helps to decrease the dangerous oxidation of LDL cholesterol that leads to atherosclerosis.42

Pomegranate Peel Extracts

Pomegranates are known to be one of the healthiest fruits on earth. Extracts from pomegranate peel have a variety of anti-inflammatory effects that are especially beneficial for people at risk for cardiovascular disease.43

Studies show that pomegranate peel extracts increase resistance to oxidative stress in animals with high cholesterol levels.44,45 They reduce the accumulation of oxidized LDL cholesterol in so-called “foam cells” that are found in the very early stages of atherosclerosis, shrinking plaque sizes by up to 39%.46

They also powerfully promote the flow of cholesterol out of these cells by 147%. This important action helps reduce the overall cholesterol burden.45

Walnut Extracts

Walnuts are one of the most important food sources of polyphenols.47 Extracts from these flavorful nuts have been found to inhibit LDL oxidation in human plasma, an action that reduces the amount of this highly inflammatory compound.48 Walnuts also induced a 55% reduction in plaque development in the aorta of supplemented mice, while also lowering plasma triglycerides by 36%, cholesterol by 23%, and prothrombin (an enhancer of blood clot formation) by 21%, compared to controls.49

Combined, all of these foods provide a broad spectrum of unique polyphenols that provide many of the key health benefits of the Mediterranean Diet. While it may be difficult to obtain all these food groups in a given day, there are now extracts that provide concentrated polyphenol benefits to induce the benefits of the Mediterranean diet.


Higher Urinary Polyphenols<br> Promote Longer Survival
FIGURE: Higher Urinary Polyphenols
Promote Longer Survival2

Survival graph showing the probability of
survival at each year of the 12-year study,
according to low (red line), middle (blue line)
and high (green line) urinary polyphenol levels.
GAE (gallic acid equivalents) are a
standardized measure of polyphenol activity.

A New England Journal of Medicine paper showed that the Mediterranean diet can reduce the risk of cardiovascular events—including death—by 30%.

This was not an epidemiologic study showing simple correlation, but instead was a true intervention study, from which one can conclude that the diet produced the observed health benefits.

Follow-up studies showed that a large part of the cardiovascular protective effect of the Mediterranean diet comes from its high concentration of polyphenols.

Life Extension has long recommended that people make every attempt to follow a Mediterranean-style diet. Studies cited in this article provide startling validation that eating these healthy foods confers significant longevity benefits.

It can be challenging, however, to adhere constantly to the Mediterranean diet. By supplementing with specific polyphenols, we can be sure we’re getting enough of these critical plant nutrients to benefit from their cardioprotective effects.

If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.


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