Cardio Protection – Resveratrol, Quercetin and Heart health
Diagnosed heart disease, has made scientists more conscious of lifestyle and other major cardiac risk factors: rich foods, no exercise, hypertension, and an apple shaped, moderately obese body
Heart attack is the number one killer in the United States. Exploring what causes heart attacks, we find the best ways to prevent them, are natural approaches-in particular the use of polyphenols such as resveratrol, quercetin, and other compounds found in red grape skins may provide valuable new protection for the heart, along with diet and exercise.
While the news about red wine might sound great if you enjoy a glass of red wine with your evening meal, doctors are wary of encouraging anyone to start drinking alcohol. That’s because too much alcohol can have many harmful effects on your body.Still, many doctors agree that something in red wine appears to help your heart. It’s possible that antioxidants, such as flavonoids or a substance called resveratrol, have heart-healthy benefits.
As people’s life spans have increased and our diet has moved away from what we ate thousands of years ago as hunter-gatherers, heart disease has increased, but it was not until 1912 that we began to understand the mechanisms involved. That year Professor James Herrick, a physician at the University of Chicago, published his landmark paper “Clinical Features of Sudden Obstruction of the Coronary Arteries.” In it he correlated autopsy findings of blocked arteries in the heart with patients who had also complained of chest pain over several months or years and then died suddenly. Dr. Hemick coined the term “heart attack,” or myocardial infarction, to describe what occurs when a part of the heart muscle dies or is damaged due to an inadequate supply of oxygen-rich blood to that area.
“The origins of coronary heart disease lie in the reduced passage of blood within the coronary arteries.” He used the term atherosclerosis, from athero (meaning “paste”) and sclerosis (”hardness”), to describe coronary arteries filled with calcium, blood clots, and cellular debris that blocked the coronary arteries to produce heart disease.
Until quite recently, scientists accepted the idea that a heart attack was caused primarily by a plumbing problem, much the way that mineral deposits and rust build up inside water pipes over time. The human heart beats roughly one hundred thousand times per day, cycling six quarts of blood through the sixty thousand miles of blood vessels in our bodies. It stood to reason that deposits would accumulate in this elaborate system and eventually cause blockages, leading to a heart attack.
The New Theory of Heart Disease
Coronary artery disease, or hardening of the coronary arteries, is indeed the cause of most heart attacks. The problem is that as much as half the time, sudden death is the first symptom of heart disease. It was well established that elevated cholesterol levels, high blood pressure, diabetes, tobacco use, obesity, and sedentary lifestyles were all major risk factors associated with progressive artery blockage, but they showed up in only half of all fatal heart attacks. So what caused the rest?
Scientists began to look beyond the composition of the clots blocking blood vessels to the lining of the vessels themselves, called the endothelium. Its functions include regulating inflammation and immune reactions, the tone of blood vessels (their ability to contract and widen, or dilate), clotting, the formation of new blood vessels, and so on. Like the skin on the outer surface of the body; the endothelium is subject to a multitude of disease processes as it performs its vital regulatory functions. So important is the study of the endothelium that this research has become the basis of a new frontier called endotheliology. As scientists struggle to find ways to avert heart attacks, which kill more than seven million people worldwide each year, the endothelium seems to lie at the heart of the problem.
Resveratrol might be a key ingredient in red wine that helps prevent damage to blood vessels, reduces “bad” cholesterol and prevents blood clots.
Most research on resveratrol has been done on animals, not people. Research in mice given resveratrol suggests that the antioxidant might also help protect them from obesity and diabetes, both of which are strong risk factors for heart disease. However, those findings were reported only in mice, not in people. In addition, to get the same dose of resveratrol used in the mice studies, a person would have to drink over 60 liters of red wine every day.
Research also shows that resveratrol could be linked to a reduced risk of inflammation and blood clotting, both of which can lead to heart disease. More research is needed before it’s known whether resveratrol was the cause for the reduced risk.
Many components circulating in the blood can damage the arteries’ inner lining. These include glucose (sugar), trans-fatty acids, lowdensity lipoproteins (LDLs) , free radicals, and cytokines~signaling molecules that can turn inflammation on and off. To prevent heart diseaseand understand the role of xeno factors in prevention, we need to understand the five stages leading to a heart attack.
(1) the accumulation and oxidation of fat by free radicals; (2) inflammation within the blood vessel itself; (3) a markedly decreased vascular tone and decreased elasttcity of the blood vessels; (4) increased clotting that results in coronary thrombosis, or the sudden obstruction of the coronary arteries, as described by Herrick; and (5) the damage or death ofthe heart muscle itself
Let’s take a close look at the remarkable promise that xeno factors offer by fighting heart disease at each of these five stages.
Xeno Factors, Polyphenols – Resveratrol and Quercetin and Cardio Protection
Heart disease, cancer, Alzheimer’s disease, and many forms of arthritis all have one common link to our age-old immunological defense mechanism: inflammation. Inflammation is the body’s first defense against infection and trauma. Now scientists have finally connected the dots, giving researchers renewed hopes that a remedy for inflarnmation could possibly prevent the many major diseases that ail us.
Drug companies are spending billions of dollars on researching new drugs and are exploring new ways to use existing drugs. Celebrex, a so-called COX-2 inhibitor used primarily for arthritis because of its anti-inflammatory effects, is being evaluated to see if it can prevent breast cancer, slow memory loss in Alzheimer’s disease, and eliminate polyp development in the intestines. Statin drugs, thought to reduce the incidence of heart attacks by reducing cholesterol, also reduce inflammation; this reduction may be their primary cardio-protective mechanism.
Aspirin, the grandfather of anti-inflammatory drugs, known for reducing the incidence of heart attacks, is also being tested on colon cancer and Alzheimer’s disease.
And very recently; natural substances high in xeno factors-resveratrol, quercetin, catechin, and the other polyphenol compounds-have shown remarkable early signs of effectiveness against inflammation.
Stage 1: The Antioxidant Effect: Reducing Free Radicals
Diets high in fat, particularly from meat and hydrogenated vegetable oils, or so-called trans-fatty acids, found abundantly in French fries, some cakes, and margarine, are extremely damaging to the endothelium. In fact, trans fats appear to increase the risk of heart disease more than any other food product, even at very low levels. A 2 percent increase in calories from trans-fatty acids is associated with a 23 percent increase in the incidence of coronary artery disease. It is no wonder that the New York City Department of Health required 20,000 restaurants and 14,000 food suppliers to eliminate partially hydrogenated oils from their food. Other states are following suit, and Denmark and Canada are actually considering legislation to eliminate all industrially produced trans-fatty acids from their food supply.
After being processed by the liver, fats accumulate in the blood in the form of cholesterol and triglycerides. There are two primary types of cholesterol molecules: LDL, or “bad” low-density lipoprotein; and HDL, or “good” high-density lipoprotein, which has been referred to as the “arterial wall garbage barge” because of its ability to haul away bad cholesterol. from clogged arteries.
If the balance tips toward LDL and other toxic food by-products, the endothelium becomes irritated and causes microscopic cracks to develop in the lining of the blood vessel. These cracks release free radicals that oxidize or degrade the LDL. The accumulation of free radicals in oxidized LDL leads to the next stage of coronary disease.
When an oxygen molecule is added to LDL cholesterol, this creates a fatty substance that can attack the membranes of surrounding cells, particularly the endothelium. This deterioration of membrane lipids (fats), known as lipid peroxidation, is extremely destructive to the blood vessel lining. Our bodies use antioxidants in our diet to counter these destructive effects.
Scientists evaluated the effects of red wine on LDL. They found that the people in the treatment group, who drank one and a half glasses of red wine per day, lowered their level of lipid peroxide (the toxic material) by an average of 40 percent. They also found that an alcohol-free powder of a red wine polyphenol extract had similar antioxidant effects, both in the blood and in LDL cholesterol. This confirmed that although alcohol in red wine may contribute to cardio protection, the main antioxidant protection comes from polyphenols.
There are several mechanisms for this protection. As free-radical scavengers, these xeno factors prevent free radicals from “stealing” electrons from the membranes of normal cells, and this action in turn prevents any destructive effect. Other studies have shown that polyphenols bind to LDL cholesterol, thus protecting it from peroxidation. The bottom line is that the polyphenols found in xeno factors significantly inhibit or prevent the first stage in the development of a heart attack through their antioxidant effect.
Stage 2: The Anti-inflammatory Xeno Effect
When oxidized LDL and fat just under the endothelium accumulate, they attract white blood cells circulating in the bloodstream. These white cells, called macrophages, proceed to ingest the cholesterol in an attempt to remove it. The now fat-laden microphages (known as “foam cells” because they appear plump and white under the microscope) create a significant inflammatory reaction. Smooth muscle cells form a cap over the injury site in the blood vessel lining; calcium accumulates here and forms a material similar to bones-hence the term “hardening of the arteries”. The word plaque refers to this combination of foam ceJls, smooth muscle cells, and lipid accumulation, which has a cheesy appearance.
The discovery of nuclear Jactor kappa B (NF- KB) is critical in the understanding of inflammation. The NF-KB molecule is a protein that acts as a switch to turn inflammation on and off in the body Known as the body’s “smoke detector,” it can detect substances such as infectious agents, free radicals, and other bad actors.In response, it turns on particular genes that promote production of inflammatory cytokines that in turn try to kill or isolate the invading agent through the inflammatory response.
When the membranes of the surrounding cells sense the toxic debris of the plaque, NF-KB facilitates the production of chemicals that promote and maintain the normally protective inflammatory state. These agents attract defensive white blood cells to the site of inflammation and enhance cellular proliferation and growth. In the case of the coronary arteries, however, the inflammation response persists and will not stop until the muscle cells just under the endothelium grow over the site of irritation in an attempt to cover the debris. It is through blocking or inhibiting NF-KB activity that aspirin; nonsteroidal anti-inflammatories like Celebrex, Aleve, and ibuprofen; and natural compounds like white willow bark work to block inflammation. Multiple lines of laboratory studies indicate that xeno factors such as resveratrol, quercetin, and others act as potent anti-inflammatory agents through a similar action on NF-KB.
Stage 3: The Vascular Dilation Effect- The coronary arteries widen and constrict to vary blood supply to the heart muscle under different circumstances. When we walk up a steep hill or exercise vigorously, our blood vessels automatically dilate to bring more oxygen-carrying blood to the heart. When the physical activity is over, the blood vessels return to a more normal size. Artery walls encrusted with plaque lose this flexibility. A substance called nitric oxide, produced by the endothelium, promotes relaxation and constriction of the arterial smooth muscle.
One of the earliest signs of atherosclerotic changes, or hardening of the arteries, is the inability of the endothelium to make nitric oxide, which would allow the arteries to dilate. Because of the general protective effects of polyphenols, scientists set out to determine if these compounds might enhance nitric oxide production. Indeed, it has been confirmed that resveratrol enhances the production of nitric oxide, allowing arteries to dilate in times of need.
The xeno factors also block a substance called endothelin-l (ET-l), which is a potent constrictor of blood vessels and also stimulates smooth vascular muscle cells to cover up the plaque within the blood vessel. Inhibiting ET-l production, protecting against atherosclerotic changes in the blood vessel, blocking vascular constriction, and enhancing vascular enlargement are all ways in which natural xeno factors work to provide cardio protection at this third stage of cardiac disease development.
Stage 4: The Xeno Factor and Blood Clotting
As material continues to build up inside the blood vessel, it can accumulate to the point where blood flow is markedly reduced and then finally blocked. More commonly, however, the arterial plaque can break up, exposing the underlying cellular debris to the rapidly flowing bloodstream. The body senses this as an injury and sends platelets, one of the main components of blood, to the injured area to form protective clots. These sticky platelets quickly pile up. A sudden heart attack occurs when blood flow is abruptly cut off by the platelet thrombus, or clot, leading to the death of heart muscles that depend on richly oxygenated blood for survival.
Stage 5: Stopping the Heart Attack
As we’ve seen, a heart attack occurs when a coronary artery no longer supplies blood to a particular part of the heart. Heart failure, which is often related to a heart attack, results when the heart muscle is unable to pump blood at a rate that meets the needs of the body’s tissues. In essence, if the pumping action of the heart is too weak, the body can be starved of blood-and therefore oxygen. With heart failure, the heart enlarges, its chambers dilate, and the heart’s life-sustaining ability to pump deteriorates.
Scientists were investigating the mechanism of heart failure when they found that a specific enzyme found in cardiac cells is activated by free radicals, calcium, and magnesium released by cellular injury from a heart attack. When this enzyme,poly (ADP-ribose) polymerase-l (or PARP), is overactivated, it results in heart cell death. It also suppresses the heart cell’s mitochondria, or nucleic power plants, leading to an energy deficit in cells that survive.
In studying how PARP activation causes cardiac cell death, these scientists discovered a direct link to the SIRTI enzyme: PARP reduces the activity of SIRTl. Could the same process also work in reverse, to the benefit of the heart? Dr. Pillai and his colleagues were familiar with the work of Guarente, Sinclair, and Baur. In 2006 they too studied activation of the sirtuin enzyme with resveratrol and discovered that it indeed protected the heart cells against PARP-mediated cell death. SIRTI activation helped preserve cell function.
Bezstarosti and his associates from the Erasmus Medical Center in the Netherlands reported the remarkable result that animals pretreated with resveratrol and then subjected to heart attacks showed a decreased myocardial death rate compared with animals not administered resveratrol.
Another study evaluated the ability of a red wine extract to decrease the electrical irritability of a heart muscle cell which concluded that both resveratrol and quercetin could significantly inhibit abnormal electrical flow through a heart muscle cell.
In summary, xeno factors, natural products readily available in our food, can help protect us against heart disease at every stage in its development, and can help ameliorate its life-threatening effects when a heart attack occurs.
Unfortunately, most people do not know about these xeno factors.
Prevention is still the key to survival. The United States performs three times as many invasive heart procedures per one hundred thousand people as France, Japan, and Great Britain yet still has the highest death rate from heart disease. Contrary to popular belief, although these heart surgeries may decrease symptoms, they don’t decrease heart attacks or extend life for most patients.
Quitting smoking, lowering blood pressure, and reducing other known health risks have prevented as many heart deaths over the last twenty years as have costly high-tech treatments.
Risk reduction plus supplementing a healthy diet with xeno factors like resveratrol and quercetin may be the optimal preventive strategy for heart disease.