veryone knows that medicine is big business, and nowhere is this more true than in the field of cardiac care. The statistics on cardiovascular disease and its impact on the health (and finances) of Americans are frightening. Over 60 million Americans suffer from some form of cardiovascular disease, and a substantial portion of them, 12.6 million, are victims of coronary artery disease, or CAD.

In terms of mortality, the numbers are just as alarming. CAD is the single leading cause of death in the United States; it is estimated that it will kill over 600,000 Americans this year alone. The financial impact of heart disease on heath care costs is also staggering, with expenditures running over $200 billion a year.

One reason why so much money is spent on heart disease is that in this country, surgery remains one of the most common types of treatment. Among the most prevalent procedures is the coronary artery bypass graft, or CABG. This operation is performed on over 300,000 people a year in the United States, at an average cost of $45,000 each. Doing the math, that comes to $13.5 billion annually.

Surgery Is Not a Cure For Heart Disease

Although traditional medicine would have you believe that this is money well spent, the truth is that CABG surgery is not a cure for CAD. In fact, it has some potentially serious and even life-threatening side effects. First, although this surgery is done to repair the heart, the operation itself can cause heart damage due to constriction of the blood vessels that nourish the heart.

Furthermore, CABG surgery can also cause brain damage. A study published in the New England Journal of Medicine evaluated over 2000 patients who had had this operation.¹ It was found that over 6% of these patients had devastating neurological side effects, including strokes, seizures, and deterioration of intellectual functioning. In fact, the authors concluded that "Adverse cerebral outcomes after coronary bypass surgery are relatively common and serious; they are associated with substantial increases in mortality, length of hospitalization, and use of intermediate or long-term care facilities."

Arginine Produces Nitric Oxide

Fortunately for people who suffer from heart disease, there is a growing body of solid scientific evidence that an amino acid, L-arginine (arginine for short) can significantly protect against the development of coronary artery disease and thus help avoid the need for CABG surgery. In addition, arginine can help to protect the heart from some of the harmful effects of the surgery when it is performed.

So how does arginine work its wonders on the human heart? The answer is nitric oxide (NO), a simple gas molecule made up of nitrogen and oxygen. Arginine is the body's primary source of NO, a compound so important that the 1998 Nobel Prize in medicine was awarded to the three scientists who discovered its role in human physiology. NO penetrates and crosses the cell walls of almost all cells in the human body, and it helps regulate many cellular functions.

Nitric Oxide Regulates Endothelial Function

In the circulatory system, NO is vitally important because it regulates the tone of the layer of smooth, tightly layered cells, called endothelial cells, that line the inside of blood vessels in the heart and throughout the body. If these endothelial cells become dysfunctional, they can cause spasms or constrictions of the blood vessels.

One of the major problems in CAD is the predominance of such dysfunctional endothelial cells in the coronary arteries, which supply blood to the heart muscle. When these arteries become constricted, a person with CAD can experience angina pectoris (angina for short), a heart pain that is often the first sign of an impending heart attack. Only in the last few years have scientists discovered that it's a deficiency of NO in the coronary arteries' endothelial cells that significantly contributes to their dysfunction. Scientists have also discovered, however, that supplementation with arginine, the amino acid from which the body makes its NO, can help protect against CAD-induced damage to the heart.

Arginine Is Vital for a Healthy Heart

One of the first studies to examine the effects of arginine on coronary endothelial function in humans was done at the Mayo Clinic in 1998. There, researchers gave patients either 9 grams of arginine or placebo every day for 6 months.² At the end of that time, the patients who had been taking arginine had significantly better coronary blood flow than those who had been taking placebo (the controls). The authors concluded that "Long-term oral L-arginine supplementation for 6 months in humans improves coronary small-vessel endothelial function in association with significant improvements in symptoms and a decrease in plasma endothelial concentrations."

Other studies, done in both Europe and the United States, have shown how arginine can improve heart function in patients with CAD and a history of angina. One study examined the effects of giving just a short course (6 grams/day for 3 days) of arginine to patients with angina who had had a heart attack, to see if the arginine could increase their exercise tolerance.³ Compared to the control patients, those who received arginine had statistically significant increases in their exercise capacity on a treadmill.

Another study looked at 52 patients with angina.⁴ They were given 15 grams/day of arginine or placebo before their exercise tolerance was measured, using a stationary bicycle. After only 10 days, the patients taking arginine were able to exercise longer and without pain when compared to the controls. The authors concluded that "L-arginine can be recommended as an adjunct in the treatment of patients with ischemic heart disease." (Ischemic means caused by inadequate blood supply.)

How CABG Surgery Is Done Coronary artery bypass grafting surgery is one of the most complex "routine" operations performed in the United States today. The goal is to remove and replace the arteries that supply the heart muscle with life-sustaining blood. Over a person's lifetime, arteries in the heart (and throughout the entire body) can become clogged by fatty, cholesterol-laden plaques. In CABG surgery, a blood vessel, most commonly the saphenous vein from the leg, is removed and sewn into place around the heart. The idea is for this "new" blood vessel to bypass the plaque-containing coronary artery and allow blood again to flow freely to the heart. To perform this operation, the surgeon must literally split the patient's chest wide open to allow access to the heart and surrounding blood vessels. Furthermore, the heart must be completely stopped for a long period, during which the patient is kept alive by a heart-lung machine, which keeps oxygenated blood flowing throughout the body. The entire procedure can take anywhere from two to six hours. After the surgery, patients are in the intensive care unit for two to three days, and they are often not released from the hospital for another four to five days. People who have desk jobs can usually return to work after four to six weeks. There is no guarantee of permanent benefit from CABG surgery, and even in the hands of the most competent surgeons, 20 to 30% of all patients who have had it will need to undergo the entire, grueling procedure again within ten years.

Finally, a study done in 2000 looked at the effects of arginine in patients with CAD who underwent a procedure in which they were given a very low dose of a radioactive isotope (thallium-201) as a means of visualizing the blood flow in their coronary arteries.⁵ With this test, doctors can determine the blood flow to the heart while the patient is exercising. The study showed that patients given arginine were able to exercise longer, and the thallium-201 scan showed that they had better blood flow to the heart when compared to the control patients.

Arginine Helps Protect Against High Cholesterol

High cholesterol levels (hypercholesterolemia in medical jargon) are also known to contribute to the development of CAD through various mechanisms. One such mechanism is a reduction in the endothelial-dependent dilation of heart blood vessels, and another is oxidative stress caused by harmful free radicals.

It has been found that supplementation with arginine can reverse these damaging effects of high cholesterol on the heart. A study done in 1992, e.g., looked at the effect of giving arginine to patients who had endothelial dysfunction due to hypercholesterolemia.⁶ After IV (intravenous) infusion of arginine, coronary-artery blood flow increased significantly.

A later study examined 27 patients, aged 18–40, who had significantly elevated cholesterol levels.⁷ They were given 7 grams of arginine or placebo 3 times per day. After only 4 weeks, the patients who had taken arginine showed definite improvement in blood flow.

Finally, this year, researchers examined the effects of arginine on middle-aged patients with high cholesterol levels.⁸ As in the earlier studies, those who received arginine again showed significant improvement through improved endothelial function. The authors of this study concluded that "The augmentation of NO production/release induced by L-arginine may act as an antioxidant, and contributes to the improvement of endothelial function in hypercholesterolemic subjects."

Arginine Protects the Heart During CABG Surgery

Despite all the knowledge now available on how to prevent or treat CAD nonsurgically, some people will still wind up needing CABG surgery. Even for those people, supplementation with arginine can be potentially life saving. As mentioned above, CABG surgery can sometimes cause a paradoxical constriction of the heart's blood vessels.

Arginine Can Boost Immune Function . . . and Your Sex Life! Besides helping to protect against heart disease and the dangers of CABG surgery, arginine has a number of other positive effects on human health. It is now accepted, even by traditional medicine, that this versatile amino acid can significantly improve the functioning of the immune system. Arginine is now routinely given in hospitals across the United States to patients who are severely burned, who have sepsis (a systemic, life-threatening infection), or whose immune systems are severely stressed. One need not be hospitalized, however, to benefit from the immune-boosting effects of arginine. It's known that this amino acid participates in protein synthesis, the production of white blood cells, and the proliferation of protective killer T cells. Take away arginine, and the immune system would literally grind to a halt. As a delightful bonus, arginine can also add a "boost" to one's sex life. It does this by increasing the amount of nitric oxide, the same molecule that is so vitally important for proper cardiac function. In the sexual arena, nitric oxide increases blood flow to the penis in men and to the clitoris in women. Because of this, men who take arginine often have stronger, firmer erections, while women can gain increased clitoral sensitivity. When you put these two together (so to speak), you can see why arginine has become a very popular supplement indeed.

A study published in 1999 looked at the effects of arginine on patients undergoing CABG surgery.⁹ Twenty patients having this operation were divided into two groups, one receiving IV arginine and the other receiving placebo. The group that received arginine had significantly less CABG-induced constriction of their blood vessels, and they also showed more stable blood flow in the grafted blood vessel.

A similar study published this year used a molecule called troponin T, which is a highly sensitive marker of heart damage, to gauge the protective effects of arginine on the CABG patients.¹⁰ During a 2-year period, 200 such patients received either IV arginine or placebo. The results of the study were again impressive: in the authors' words, "L-arginine . . . is associated with reduced release of biochemical markers (troponin T) of myocardial damage, suggesting improved myocardial protection."

Arginine for a Healthier, Happier Life

Cardiovascular disease is a debilitating, crippling, and life-threatening disease that strikes down over 1600 Americans each day. Through a healthy diet, regular exercise, and supplementation with products that contain L-arginine, you can significantly reduce the odds of your becoming part of that grim statistic. Arginine, which is arguably the mot important of all the amino acids, can help you lead a longer, healthier, happier life by helping to protect the most important muscle in your body: your heart.

References

1. Roach GW, Kanchuger M, Mangano CM, et al. Adverse cerebral outcomes after coronary bypass surgery. New Engl J Med 1996;335(25):1857-64.
2. Lerman A, Burnett JC, Higano ST, et al. Long-term L-arginine supplementation improves small-vessel coronary endothelial function in humans. Circulation 1998; 97(21):2123-8.
3. Ceremuzynski L, Chamiec T, Herbaczynska-Cedro K. Effects of supplemental oral L-arginine on exercise capacity in patients with stable angina pectoris. Am J Cardiol 1997;80(3):331-3.
4. Sozykin AV, Noeva EA, Balakhonova TV, et al. Effect of L-arginine on platelet function, endothelial function, and exercise tolerance in patients with stable angina pectoris. Terapevticheskii Arkhiv 2000;72(8):24-7.
5. Fujita H, Yamabe H, Yokoyama M. Effect of L-arginine administration on myocardial thallium-201 perfusion during exercise in patients with angina pectoris and normal coronary angiograms. J Nucl Med 2000; 7(2):97-102.
6. Creager MA, Gallagher SJ, Girerd XJ, et al. L-Arginine improves endothelium-dependent vasodilation in hypercholesterolemic humans. J Clin Invest 1992; 90(4):1248-53.
7. Clarkson P, Adams MR, Powe AJ, et al. Oral L-arginine improves endothelium-dependent dilation in hypercholesterolemic young adults. J Clin Invest 1996;97(8):1989-94.
8. Kawano H, Motoyama T, Hirai N, et al. Endothelial dysfunction in hypercholesterolemia is improved by L-arginine administration: possible role of oxidative stress. Atherosclerosis 2002;161(2): 375-80.
9. Wallace AW, Ratcliffe MB, Galindez D, Kong JS. L-Arginine infusion dilates coronary vasculature in patients undergoing coronary bypass surgery. Anesthesiology 1999;90(6):1577-86.
10. Carrier M, Pellerin M, Perrault LP, et al. Cardioplegic arrest with L-arginine improves myocardial protection: results of a prospective randomized clinical trial. Ann Thoracic Surg 2002;73:837-42.

Dr. Rosick is an attending physician and clinical assistant professor of medicine at Pennsylvania State University, where he specializes in preventive and alternative medicine. He also holds a master’s degree in healthcare administration.