Phenolic Compounds May Explain Mediterranean Diet Benefits

"It could be that the beneficial effect of the Mediterranean diet on cardiovascular disease and arteriosclerosis depends on the synergistic effects of the different nutrients that constitute complete foods and, as an example, virgin olive oil is more than fat because it is a real juice with other healthy micronutrients," said Francisco Pérez Jiménez, M.D., Ph.D., from the Reina Sofia University Hospital in Córdoba, Spain.

The researchers, including lead author Juan Ruano, M.D., Ph.D., fed breakfasts including olive oil (that was either high or low in phenolic content) to 21 study participants (5 men, 16 women) who had high cholesterol levels, but were otherwise apparently healthy. The functioning of the endothelium (the inner lining) of small blood vessels of the fingers (instead of "in the arms") of participants and the concentrations of certain components in blood serum, including nitric oxide, improved after the polyphenol-rich breakfast.

"This is the first study that shows a direct benefit of an olive oil with high content in phenolic compounds on endothelial function in vivo," Dr. Pérez Jiménez said.

After fasting overnight, the participants reported to the hospital, where they ate a breakfast of 60 grams of white bread with 40 milliliters of virgin olive oil, a relatively high-fat meal. The meals also included vitamin A supplementation. Over the next four hours, blood samples were taken and the researchers used Doppler laser to measure endothelial responses to sudden changes in blood flow, which were produced by inflating and then deflating a blood pressure cuff. The response is known as ischemic reactive hyperemia. Poor responsiveness to this sort of blood flow test is considered an early warning sign of cardiovascular disease. Previous studies have linked high-fat meals to poor endothelial function lasting for several hours after eating.

In order to focus on the role of phenolic compounds, the researchers put each participant through the process twice in a randomized order, once using olive oil naturally high in phenolic compounds (400 parts per million) and once with the same brand of olive oil that had been processed to remove most of the phenolic compounds (80 parts per million remaining).

"We think, looking at our results, that the reduction in oxidative stress and the increase in the nitric oxide bioavailability are behind the observed improvement in ischemic reactive hyperemia," Dr. Pérez Jiménez said.

Dr. Pérez Jiménez said that olive oil may be superior to seed oils because it is a natural juice, pressed from the olives, so it does not go through the type of processing needed to extract oil from seeds, such as sunflowers, soybeans and rapeseeds. Nevertheless, he said further studies should be done to investigate whether phenolic compounds in olive oil can be linked to improved health outcomes.

"Although our study shows a direct benefit of an olive oil with high content in phenolic compounds on endothelial function in humans, carefully controlled studies in appropriate populations, or with a large sample size, are required to definitively establish the in vivo antioxidant properties of these components in relation to cardiovascular disease outcomes. On the other hand, some data suggest that endothelial dysfunction could be a surrogate end point for prediction of cardiovascular risk, but we need more information on the utility of the different methods to evaluate endothelial dysfunction," Dr. Pérez Jiménez said.

Robert F. Wilson, M.D., from the University of Minnesota in Minneapolis, who was not connected with this study, noted that health benefits of a Mediterranean diet were described over 50 years ago.

"This study demonstrates one possible mechanism by which olive oil rich in phenolic substances improves the functioning of the circulation. The authors found that after test subjects took olive oil spiked with phenolic compounds, their blood vessels could dilate better, which could improve blood flow. These findings are particularly interesting because similar studies after high fat meals, like a burger and fries, showed impairment of normal blood vessel functions," Dr. Wilson said.

Dr. Wilson pointed out that not all olive oils have a high phenolic content.

"So these results might not be true for all olive oil on the shelf at the grocery store," he said.

Juan J. Badimon, Ph.D., F.A.C.C., from the Mount Sinai School of Medicine in New York, New York, who also was not connected with this study, said it was well-designed and will help address controversy about whether olive oil benefits or impairs blood vessel health.

"One of the beauties of this study is that using a randomized, sequential, crossover study, so that the same patients were exposed to the same oil, once with low phenolic content and the other with high phenolic content, the only variable in this study is the phenolic content of the olive oil," Dr. Badimon noted. "These results indicate that a very small change in diet, like using olive oil with a high phenolic content may have a significant impact in the progression of atherosclerosis."

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Disclosure

This study was supported by the Spanish Plan for R&D (SAF 03/05770 to Dr. Pérez-Jiménez), Plan Andaluz de Investigación (to Dr. Lopez-Miranda and Dr. Pérez-Jiménez), Diputación Provincial ( Córdoba), Denomination of Origin Boards of Baena and Priego de Córdoba, and Cultural Foundation "Reina Sofia-Cajasur."