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The Disease-Preventive Power of the Mediterranean Diet

July 2005

By Dale Kiefer

Olive Polyphenols and Cholesterol

Wondering whether hydroxytyrosol’s LDL-protective effect could be reproduced in humans, researchers in Spain solicited healthy volunteers to participate in a randomized, double-blind, controlled crossover study. Subjects consumed three different extra-virgin olive oils with incrementally greater levels of polyphenols. At the end of each study period, blood plasma levels of LDL were examined for degree of oxidation. Levels of beneficial HDL (high-density lipoprotein) were also assayed. As the polyphenol content of the olive oil increased, LDL oxidation decreased. Polyphenol-rich olive oil also raised HDL levels. Both effects are associated with an improved cardiovascular risk profile.37 Other researchers have observed similar results demonstrating the ability of olive oil polyphenols to prevent damaging oxidative processes.52-54,58

In a variation of this study, Spanish researchers tested the effects of feeding three olive oils with incrementally greater levels of polyphenols to a group of healthy male volunteers. Subjects in this randomized, double-blind study consumed standardized doses of polyphenol-rich olive oil. After a washout period, subjects were blindly switched to another polyphenol-rich olive oil formulation. The researchers assessed plasma LDL oxidation and the activity of glutathione peroxidase and other markers of antioxidant status. Oxidized LDL decreased, glutathione antioxidant activity increased, and HDL levels increased in the participants. These effects were proportionally greater as olive polyphenol content increased. All of these changes reflect improvements in surrogate markers of cardiovascular health.39

Another study conducted by researchers at the same Barcelona medical research facility showed similar results. Markers of oxidative stress, implicated in the development of cardiovascular disease,41 were assessed after ingestion of a single dose of polyphenol-rich extra-virgin olive oil. LDL’s resistance to oxidation improved after consumption of the polyphenol-rich olive oil,40 while glutathione-related enzyme activities also improved.40 Other studies have reported similar results.38

Sesame Lignans: Phytonutrient Power

Like polyphenols from olives, sesame seeds are rich in compounds with powerful antioxidant properties. Sesame seeds contain lignans, a class of chemicals known as phytonutrients that are responsible for a range of health benefits.

For example, lignans have the ability to modulate immunity and may prevent various types of cancer.66-73 When Scandinavian researchers fed the sesame lignan sesamin to laboratory animals, they documented an increase in bioavailable levels of the important antioxidant gamma tocopherol, a potent and biologically active form of vitamin E.74 Japanese researchers have shown that when sesamin is added to the diets of animals bred for their susceptibility to hypertension and stroke, various markers of cardiovascular damage are significantly improved, especially among salt-sensitive hypertensive animals.75

In a similar experiment, scientists fed vitamin E, sesamin, or both to animals prone to hypertension and stroke. A control group received normal feed. As they aged, the control animals developed high blood pressure and elevated levels of an oxidative stress marker, and exhibited an increased tendency to develop clots that could precipitate stroke. By contrast, the animals fed sesamin, vitamin E, or a combination of the two nutrients were significantly protected from these deadly conditions.76

Reducing Inflammation

More recent work on the mechanisms underlying these effects indicates that sesamin reduces levels of inflammatory prostaglandins and leukotrienes, immune system components that are associated with pathological inflammatory conditions.77 Many scientists now believe that low-grade inflammation is an underlying condition that contributes to a broad range of degenerative diseases such as atherosclerosis, heart disease, arthritis, cancer, Alzheimer’s disease, and Parkinson’s disease.78-84 Omega-3 fatty acids are also known to reduce inflammation,14,85 and recent research indicates that they may increase levels of anti-inflammatory compounds in the bloodstream.21,86-87

Sesame seed components, including sesamin and sesamolin, may also reduce the effects of reactive oxygen species, a class of highly reactive, damaging free radicals that are generated in response to injuries such as those caused by stroke. In an experiment designed to simulate stroke damage, Chinese scientists deprived nerve cells of oxygen in the laboratory. In cells treated with sesamin and sesamolin, cell death was reduced significantly compared to untreated cells. The scientists concluded that the sesame seed lignans may have suppressed the generation of reactive oxygen species and inhibited the release of mitogen-activated protein kinases,88 a family of immune system proteins responsible for inducing programmed cell death, or apoptosis.89 Recently, Taiwanese researchers reported findings that appear to confirm this ability of sesame lignans to intervene in apoptosis by modulating immune system signaling events.90

Lowering Blood Pressure

Sesame seed lignans may also reduce blood pressure. In an effort to document sesame’s antihypertensive effects, Japanese researchers worked with animals bred to serve as a model of human hypertension. One group of animals was fed a normal diet supplemented with sesamin, while the other group received only the normal diet. After five weeks, aortic superoxide, an indicator of cardiovascular stress, was measured in both groups. Sesamin-fed animals had lower superoxide levels and lower blood pressure; conversely, animals fed a normal diet developed hypertension and elevated levels of superoxide. The scientists concluded that sesamin may inhibit production of aortic superoxide, and that sesamin’s antioxidant activity may contribute to its ability to reduce blood pressure.91,92

Preventing Lipid Peroxidation

Sesame lignans also reduce the peroxidation of lipids. Lipid peroxidation produces harmful free radicals that can have damaging, disease-promoting effects in the body, and may precede the development of atherosclerosis. Preventing peroxidation may make lipids less likely to adhere to the lining of blood vessels, an important goal of preventive medicine.93 Researchers in Japan determined that, when fed to laboratory animals, the sesame seed lignans sesamin and sesaminol decrease lipid peroxidation and raise levels of alpha tocopherol, aform of vitamin E. Other researchers have confirmed this effect.94-96

Indian scientists found a similar effect when animals were fed sesame oil and sesamin. Despite induced oxidative stress, the animals fed sesame oil and sesamin retained high levels of tocopherols, or vitamin E antioxidants. The researchers suggested that sesame lignans may regenerate oxidized tocopherols, essentially sparing them in the body.96

Controlling Inflammation Synergistically

Synergy refers to effects produced by two or more agents that are greater than the sum of their respective individual effects. As an example, consider the benefits of adding omega-3 fatty acids to standard chemotherapy for cancer treatment. Studies have shown that omega-3 polyunsaturated fatty acids may be cancer preventive, but that they also synergize with some anti-cancer drugs to enhance tumor-killing activity.15

Recently, scientists in Brazil reported a synergistic effect on rheumatoid arthritis of DHA- and EPA-rich fish oil combined with polyphenol-rich olive oil.16 Forty-three middle-aged patients undergoing rheumatoid arthritis treatment were randomly assigned to one of three groups. In addition to standard treatment for their pain, stiffness, and inflammation, patients in group one received a placebo oil. Patients in group two received DHA- and EPA-rich omega-3 fatty acids from fish oil, while patients in group three were given a combination of fish oil and polyphenol-rich olive oil. Disease status was assessed before the beginning of the study and at three and six months. At the study’s end, fish oil was found to significantly relieve various indicators of disease progression. Duration of morning stiffness decreased, joint pain intensity was reduced, handgrip strength increased, and fatigue was lessened.

Most impressive, however, were the effects observed in the group that received both fish oil and olive oil. These patients exhibited an “accentuated improvement” when DHA- and EPA-rich fish oil supplements were used in combination with polyphenol-rich olive oil.16 While fish oil improved various parameters of inflammation, only fish oil and olive oil together provided additional improvements in duration of morning stiffness, the ability to turn faucets on and off, and patients’ subjective assessments of satisfaction with their daily living activities.