In an unprecedented breakthrough, the U.S. government's National Heart, Lung and Blood Institute (NHLBI) provided the first major multidisciplinary programmatic grant to study the effects of moderate wine consumption on cardiovascular health to the University of Alabama at Birmingham (UAB).

Specifically, the federal government has committed a large sum of money to the scientific exploration of the basic mechanistic link between moderate wine consumption and lowered risk of heart disease, which should help to clarify how individual components of wine (in particular, alcohol and principal polyphenols) can reduce the risk of coronary heart disease in certain individuals. This is of major significance, as some researchers and policy organizations have cautioned that any positive advice about alcohol and coronary heart disease can only be given if the scientific community has more extensively identified the possible molecular mechanisms involved. This article will outline the key facts about this new grant program, and explain the ongoing work by the UAB research team. The program has the potential to become an important and essential scientific cornerstone to public health and general consumer messages about moderate consumption for many years to come.

Specifics About The Grant

Last autumn, the NHLBI, part of the National Institutes of Health (NIH), awarded a $7.6 million, five-year program project grant (PPG) to the school of medicine at UAB, to examine the cellular, molecular and genetic mechanisms that enable wine components (alcohol and principal polyphenols) to potentially reduce the risk for heart disease. Dr. Francois M. Booyse, professor of medicine and director of molecular cardiology at UAB, who will lead the research efforts of more than 17 researchers, termed the grant award "a major milestone." While some government-funded research studies have investigated the health effects of moderate drinking, federal agencies have been primarily concerned over the last several decades with research investigations on the adverse effects of alcohol misuse. This new multidisciplinary grant will support numerous research projects to better identify some of the mechanisms responsible for the observed positive cardiovascular health effects, as they remain poorly defined and understood.

Important Contributions From UAB

The potential benefits of moderate wine, beer and spirits consumption have been confirmed in many scientific studies from cohorts around the world for more than two decades. Experts have concluded that these positive health effects are primarily the result of alcohol's effect on different blood lipids and coagulation mechanisms that reduce the risk of coronary heart disease (CHD) and overall CHD-related mortality. In the ongoing search to identify all the parameters involved, investigators have also found that different constituents in the beverages may be responsible for some of the observed positive health effects. In fact, since the early '90s, researchers from the U.S. and other parts of the world have published preliminary data associating polyphenols, flavonoids, and phytochemicals with certain properties that may contribute to improved health outcomes. However, most of these studies have taken place in vitro (in the laboratory) or in animals, and it is still not certain that these biological effects translate to humans. At the same time, these types of scientific explorations have contributed to the emerging evidence that these polyphenols can reduce the rate of harmful cell oxidation and favorably affect other processes that, if unchanged, could lead to atherosclerosis and heart disease.

Most recently, some of the cutting-edge research has been undertaken by a team of investigators at UAB, where new investigative approaches have identified additional mechanisms by which these constituents in the beverages may reduce the risk of certain diseases, especially CHD. The team has established its laboratory as one of the leading research groups to investigate the basic mechanisms involved in the cardioprotective effects of moderate alcohol consumption. Its ongoing research has revealed that cardio-protective results may derive not only from individual polyphenolic components per se, but also from additive or perhaps synergistic effects of alcohol and polyphenol components on a variety of vascular, cellular and haemostatic functions.

Over the past few years the team has developed new methods and approaches, using live cultured human endothelial cells and animal models, to study alcohol and polyphenol-induced changes on haemostatic function. In particular, it has focused on increased fibrinolysis (clot or thrombus lysis), which may underlie and partly contribute to the reduced risk for thrombosis and cardiovascular disease and, therefore, may afford cardioprotection. Specifically, its published research has shown that both alcohol and polyphenols are potent stimulators of increased and sustained endothelial cell fibrinolysis, thus promoting clot lysis and reducing thrombotic risk. The investigators, however, have explained that while polyphenols have been established as potent antioxidants, their duration of action is relatively short-lived. Consequently, Booyse's group has shifted its focus from the antioxidant properties of these compounds to their potential ability to alter critical gene expression and function, in particular fibrinolysis that can be sustained for 24 hours or longer.

Specifically, the researchers have examined the effects of alcohol and polyphenols on the expression of proteins and pathways that can lead to increased fibrinolysis (including, tissue-type plasminogen activator, t-PA; urokinase-type plasminogen activator, u-PA and plasminogen activator inhibitor type 1, PAI-1). T-PA is an agent that is administered after a myocardial infarction (heart attack) to facilitate clot lysis. The investigators' results have shown that both alcohol and polyphenols can alter the expression of a number of different fibrinolytic protein genes, resulting in increased fibrinolysis. This research data has been published in a series of papers in the journal, Alcoholism, Clinical and Experimental Research. Close to three dozen scientific studies, as well as presentations and abstracts, have been published by this distinguished research team, which consists of 17 investigators from various UAB departments, with expertise in the areas of cardiovascular biology and myocardial function/ metabolism.

Organizations such as The National Institute on Alcohol Abuse and Alcoholism (NIAAA), as well as the Alcoholic Beverage Medical Research Foundation (ABMRF), supported several important UAB studies that contributed to the application to the NHLBI.

Research, Education And Social Policy Value Of The Grant

Results from the UAB research program will lead to new scientific mechanisms and insights that will contribute to the shaping of science-based lifestyle messages about moderate wine, beer and spirits consumption for years to come. As Booyse and colleagues explain, "This research program will continue to identify and define the molecular regulatory mechanisms by which alcohol and polyphenols can increase fibrinolysis, in vitro, in cultured human endothelial cells and, in vivo, in animal models, to provide a well-defined molecular basis by which increased fibrinolysis can contribute, in part, to the overall cardiovascular disease protective mechanisms attributed to moderate alcohol or red wine consumption."

This rapidly emerging area of cardioprotection research, through new and continuing research efforts from this and other groups worldwide, should provide significant new insights into our understanding of the multiple divergent mechanisms that underlie and contribute to cardiovascular disease protection. These findings may have long-term public health policy implications, as policy groups such as the American Heart Association and others have called for more research discoveries in this developing field. These scientific investigations will contribute to more ongoing research, more detailed policy messages and further consumer education messages addressing the facts about moderate drinking and CHD. In summary, these ongoing initiatives will start to deal with the many unanswered questions related to the nutritional and lifestyle effects of polyphenols, so that the public can be given the most sensible advice with respect to the responsible consumption of alcohol as part of a well-balanced diet.