Polyphenols and Atherosclerotic Vascular Disease

We don't know whether Hippocrates really told us to let Food BE Our Medicine but there is truth in this concept even by the standards of contemporary medicine. When and how we might succumb to cardiovascular disease depends more on nutrition than on any other environmental factor. Yet food is not a frequent subject in medical literature. From 2010 to 2013, the 3 leading cardiology journals (Circulation, JACC and the European Heart Journal) together published only 12 full-length articles with the word NUTRITION in the title versus 104 with the word CLOPIDOGREL.

Also on the role of polyphenols one finds little information. That story really begins with solving the French Paradox, the observation by Renaud and de Lorgeril (1992) that people living in the valley of de Gers river stay healthy longer (the oldest, Mme Calment, reached 122) and have less cardiovascular disease. They suggested that local nutrients protected against atherosclerosis. In 2001, Corder, a British Experimental Pharmacologist found in wine from the local Tannat grape, that it reduced endothelin synthesis, a key polyphenol.

Then Libby, Ridker and Maseri launched in 2001 their revolutionary concept that inflammation is the primary cause for atherosclerosis, based on the conclusions by Russell Ross from autopsies in young soldiers. Meanwhile Stoclet and his group in Strasbourg unraveled in 2004 the actions of the most active polyphenols from various dietary sources.

A significant story began to unfold to which the cardiological community paid little action. Only Estruch in 2004 studied human volunteers and our group began studies in persons with the Metabolic Syndrome, prone to develop atherosclerosis, in 2005. We found that elevated levels of 2 indicators of early endothelial cell inflammation, MCP-1 and MIF could be normalized within 6 weeks of ingesting our polyphenolic product In-Vino-Veritas (IVV). We realized that the polyphenols in IVV powder stop the monocytes from being attracted to the damaged endothelial surface and to inhibit macrophages from migrating inside the endothelium and forming the "Fatty streak", the forerunner of the plaque.

Skipping the extensive and strongly positive studies on isolated cell systems, experimental animals and human volunteers with various polyphenols, there are now 3 positive large scale epidemiological studies:

1. The European Prospective Investigation into Cancer and Heartdisease (EPIC HEART) 2011, EHJ, in which 313.074 healthy persons from 8 European countries were followed for 8 yrs. It was found that those who consumed an average of 600 grams of green vegetables and/or fruits with a red skin, had 25% lower mortality than those who ate none. No mean achievement as only 18% ate these amounts over the full 8 years, mainly those from southern Europe.
2. 234, healthy individuals were followed for periods of 5 up to 26 years in a meta-analysis by Wang et al. Results published in the BMJ, 2014, showed a stepwise reduction of 5% in mortality from eating each day one or more portions of 106 grams of fruit or vegetable up to a maximum of 5 portions per day, for a total reduction of 25%.
3. Then, a randomized prospective trial by Estruch and coworkers was published in the NEJM 2013. This PREDIMED trial demonstrated that a 30% reduction in mortality could be achieved within 5 years provided healthy individuals followed a strict Mediterranean diet with red wine and 2 to 4 tablespoons of virgin olive oil, compared to those who ate their usual diet with a reduced fat intake.

Given the reality of current European food habits, these dietary requirements are difficult to achieve by most individuals. As shown in several cities in Europe, a relative deficiency in polyphenols has become likely. Hence the development of a powdered supply of essential poyphenols to supplement the diet has become a necessity, and the availability of IVV a reality. Results will be discussed.