L-Arginine: An essential amino acid to shrink coronary plaque
TYP SITE
L-arginine is the key to endothelial health. If l-arginine were a prescription medication, it would be among the hottest sellers. It's not: it's a nutritional supplement with far-reaching benefits for your plaque control program.
The plaque that took over the world!
You know the toadstools that grow in your back yard after a spring rain? That's how you should view the growth of coronary plaque. The average person with any degree of plaque—even so-called "minor" plaque—experiences a 30% per year growth in plaque size. If you've ever invested money, you know that a 30% annual rate of growth would give you the hottest stock or mutual funds around! But this frightening rate of growth cannot continue forever, or you and I would become one huge, overgrown plaque. This doesn't occur, of course, because you end up dying or having a major catastrophe like heart attack before the plaque reaches these proportions.
If we know how fast plaque will grow, can it be slowed? Or stopped? Or even reduced, i.e., can plaque shrink?
Nitric oxide-a prizewinning molecule
When we exercise, the arteries feeding the heart normally dilate. This permits a deluge of blood required to nourish heart muscle and meet the increased oxygen demands of physical exertion. But in the presence of cholesterol abnormalities, high blood pressure, inflammation, a high-saturated fat diet and sugary, refined foods, the coronary arteries constrict, choking off blood flow to the heart. This leads to repeated damage to the lining of the arteries that lays the foundation for plaque formation.
Back in 1980, Dr. Robert Furchgott was conducting experiments on rabbit arteries at the State University of New York. Entirely by accident, he noticed that arteries constricted when their inner lining, or endothelium, was removed, but dilated when the lining was intact. Dr. Furchgott theorized that the endothelium was necessary to allow the normal dilating behavior of arteries to occur, and that a damaged endothelium might not permit this phenomenon. A furious effort was sparked to identify the factor produced by the endothelium that permitted relaxation. Dr. Furchgott originally called this mysterious substance "endothelium-derived relaxation factor" or EDRF. For several years, identification of EDRF proved elusive, as is was present in active form for only mere seconds. Nonetheless, in 1986 EDRF was discovered to be nitric oxide. (Not to be confused with nitrous oxide, or "laughing gas", administered by dentists for anesthesia.) This discovery resulted in the Nobel Prize for Medicine in 1998, awarded to Drs. Furchgott, Ignarro, and Murad. Nitric oxide is now recognized to be the crucial final signaling molecule for many human processes and is the single most powerful artery dilating agent known.
L-arginine's main role in the human body is to provide the fuel for production of nitric oxide. L-arginine is metabolized by the enzyme nitric oxide synthase in the lining of the arterial wall to produce a supply of nitric oxide. Just as in Dr. Furchgott's experiments, nitric oxide relaxes the muscle cells that control the "tone" of your body's arteries. It's not unusual for vessels like the heart's coronary arteries to enlarge up to 50% in diameter when nitric oxide is readily available. Because of its extremely short life, a constant supply of nitric oxide is required to maintain relaxed arteries. Any drop in nitric oxide production and arteries constrict. Left unchecked, chronic constriction damages the artery lining, which then promotes plaque growth. Once this process begins, plaque mushrooms 30% per year. Plaque-filled arteries are less and less able to produce nitric oxide, yielding even more injury. Thus, a vicious cycle ensues.
L-arginine: No secret to the drug industry
The pharmaceutical industry is acutely aware of the power of nitric oxide and l-arginine for protection against coronary plaque. The popular prescription medicine for male erectile dysfunction, Viagra?, boosts nitric oxide. It was originally intended to be a heart drug, but proved to be more potent for the penile circulation. The search continues in earnest to develop a nitric oxide-increasing drug that will shrink plaque. Because l-arginine is a naturally-occurring substance, it is not protectable through the U.S. Patent Office. Competitors can therefore sell it freely and make development costs (hundreds of millions of dollars for a patentable drug) difficult or impossible to recover. So pharmaceutical companies have been scrambling to develop derivatives of l-arginine that are patentable. But we still have access to l-arginine and all its fabulous benefits. Just because an agent does not require a doctor's prescription doesn't mean it can't be powerful and effective. In fact, l-arginine is among the most incredible and effective supplements available to the public. (Incidentally, l-arginine also has modest penile erection-promoting effects, though the full benefit is rather slow to develop and may require 3 months.)
L-arginine shrinks coronary plaque
L-arginine is a critical ingredient in the Track Your Plaque program. In our experience, l-arginine is among the several key strategies required to gain control over coronary plaque and halt the otherwise inevitable 30% growth in plaque. Just about everyone with a heart scan score above zero (meaning that coronary plaque is present) is advised to add l-arginine to their personal program to facilitate reduction of plaque.
The scientific evidence supporting the use of l-arginine to reduce heart attack risk and to shrink existing coronary plaque is considerable. First of all, the average American ingests about 5.4 grams (5400 mg) of l-arginine per day, since it is an amino acid naturally contained in many foods. Meats of all varieties, nuts, and dairy products are rich in l-arginine, so your body is already accustomed to several-thousand milligram quantities each and every day. Many clinical studies have used intravenous l-arginine, and today intravenous l-arginine is commonly administered by endocrinologists as a provocative test of pituitary function in children with suspected short stature (slow growth). Approximately 50% of the l-arginine taken orally finds its way into the bloodstream, the other 50% being metabolized by the intestinal lining.
L-arginine can help you seize control of coronary plaque through several mechanisms:
L-arginine corrects "endothelial dysfunction"
People who have cholesterol abnormalities, are overweight, have hypertension, chest pain, increased inflammation, have a family history of heart disease, or just indulge in saturated fats frequently express an abnormal constrictive phenomenon in their arteries. Over the years, this injures the artery lining and sparks plaque growth. L-arginine is a powerful method of turning-off this response. Coronary arteries are therefore larger when l-arginine is supplemented.
L-arginine magnifies the benefits of cholesterol-lowering treatment when used along with statin agents
The conditions listed above are often associated with either low blood levels of l-arginine or the appearance of a potent, abnormal constrictor of arteries called "asymmetric dimethylarginine", an arginine-like compound that mimics the structure of l-arginine but provides none of the benefits. Blood levels of asymmetric dimethylarginine can reach 10 times normal once coronary plaque is established. When l-arginine is added to a statin (cholesterol-lowering) medication, the artery-relaxing benefits are compounded. The combination is safe and requires no modification in dosage of either the l-arginine or the statin drug.
L-arginine re-sensitizes your body to insulin
30% of all adults in the U.S. are insulin-resistant, i.e., poorly responsive to their own body's insulin, a condition often called metabolic syndrome or pre-diabetes. L-arginine can re-sensitize your body to insulin and diminish insulin-resistance.
L-arginine is anti-inflammatory
Inflammatory cells work their way from the bloodstream and into plaque, causing plaque to grow and eventually rupture, resulting in heart attack. L-arginine acts as kind of a Teflon-coating on the artery lining, preventing these cells from entering the wall.
L-arginine shrinks plaque
Few things truly shrink atherosclerotic plaque. After all, a complex mix of genetic and lifestyle factors interact over decades to create the fatty gruel that lines arteries and can erupt without warning. L-arginine is one of the few agents, prescription drugs included, that has been shown to be capable of shrinking plaque size. The so-called "statin" agents that lower cholesterol (Lipitor?, Zocor?, Pravachol?, etc.) and niacin have been shown to reduce plaque size. L-arginine is the only nutritional agent that has consistently been shown to reduce plaque size. People who suffer from angina (chest pain due to coronary blockage) or claudication (leg pain due to poor leg blood flow) obtain partial relief from their symptoms when l-arginine is taken.
The evidence is overwhelming. L-arginine is a safe, powerfully effective nutritional product that can shrink plaque.
Make l-arginine part of your Track Your Plaque program
For our purposes in Track Your Plaque, we use a dose of 6000 mg twice a day, best taken on an empty stomach. (The presence of other amino acids from protein foods seems to diminish the response.) For instance, if you take it upon arising in the morning when your stomach is empty, delay breakfast for about 30 minutes after taking your dose. Another good time to take it is at bedtime, when your last meal was likely three hours earlier.
The dose of 12,000 mg/day (6000 mg twice per day) makes capsules cumbersome to use, since most capsules contain 500 mg (24 capsules per day!). We therefore suggest the use of powdered preparations. You may need to shop around to find a powder you like at a reasonable price. There are also some very interesting l-arginine containing products manufactured by the Cooke Pharma pharmaceutical company called "Heart Bar" (available both as food bars as well as a powder).
Adverse effects of l-arginine are few. Loose stools occasionally occur with the 6000 mg dose (usually a single loose bowel movement, not repeated diarrhea). If you experience this effect, simply cut back on the dose and build up the dose gradually over several months. This tends to be mild effect (if it occurs at all) and does not lead to any long-lasting problems. If you have any active gastrointestinal diseases, particularly those associated with diarrhea or frequent loose stools, like ulcerative colitis, Crohn's disease, and malabsorption, then you should discuss the use of l-arginine with your doctor first. L-arginine can also reactivate latent oral or genital herpes or shingles, though we've had many patients successfully use l-arginine with no increase in the frequency of viral eruptions. If you have a history of cold sores, genital herpes, or shingles, you should consider speaking with your doctor about l-arginine.
L-arginine: A cornucopia of health effects
L-arginine is a fascinating, multi-faceted nutritional supplement that should be a crucial component of your heart disease prevention program. Though you'll find it in foods, when taken in greater quantities l-arginine provides a powerful boost to your health-maintenance program. Used along with a program to control cholesterol, supplemental l-arginine relaxes and dilates coronary and muscle arteries, protects the arterial wall from inflammation, prevents blood clots by blocking platelets, and can shrink plaque. There are bonus benefits outside the heart: l-arginine lowers blood pressure, increases exercise capacity (exercise longer and more vigorously), increase the vigor of erections in men, and enhances your feeling of well-being.
References:
1. Little WC, Constantinescu M, Applegate RJ, Kutcher MA, Burrows MT, Kahl FR, et al. Can coronary angiography predict the site of a subsequent myocardial infarction in patients with mild-to-moderate coronary artery disease? Circulation 1988;78:1157-1166. 2. Kuller LH, Shemanski L, Psaty BM, Borhani NO, Gardin J, Haan, MN, O'Leary DH, et al. Subclinical disease as an independent risk factor for cardiovascular disease. Circulation 1995;92:720-726.
3. Janowitz, WR, Agatston AS, Viamonte M. Comparison of serial quantitative evaluation of calcified coronary artery plaque by ultrafast computed tomography in persons with and without obstructive coronary artery disease. Am J Cardiol 1991;68:1-6.
4. Maher JE, Bielak LF, Raz JA, Sheedy PF, Schwarz RS, Peyser PA. Progression of coronary artery calcification: a pilot study. Mayo Clin Proc 1999;74:347-355.
5. Budoff MJ, Lane KL, Bakhsheshi H, Mao S, Grassman BO, Friendman BC, Brundage BH. Rates of progression of coronary calcium by electron beam tomography. Am J Cardiol 2000;86:8-11.
6. Raggi P, Callister TQ, Lippolis NJ, Russo DJ. Cardiac events in patients with progression of coronary calcification on electron beam computed tomography (abstract). Radiology 1999;213:351.
7. Furchgott, R. F., and Zawadzki, J. V. The obligatory role of the endothelium in the relaxation of arterial smooth muscle by acetylcholine. Nature 1980;288, 373-376.
8. Murad F. The 1996 Albert Lasker Medical Research Awards: Signal transduction using nitric oxide and cyclic guanosine monophosphate. JAMA 1996;276:1189-1192.
9. Calllister TQ, Raggi P, Cooil B, Lippolis NJ, Russo DJ. Effect of HMG-CoA reductase inhibitors on coronary artery disease as assessed by electron beam computed tomography. N Engl J Med 1998;339:1972-1978.
10. Achenbach S, Ropers D, Pohle K, Leber A, et al. Influence of lipid-lowering therapy on the progression of coronary artery calcification: a prospective evaluation. Circulation 2002;106:1077-1082.
11. Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M Jr, Detrano R. Quantifiction of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol 1990;15:827-832.
12. Raggi P, CallisterTQ, Cooil B, Zuo-Xiang H, Lippolis NJ, Russo DJ, Zelinger A, Mahmarian JJ. Identification of patients at increased risk of first unheralded acute myocardial infarction by electron-beam computed tomography. Circulation 2000;101:850-855.
13. Hoff JA, Chomka EV, Krainik AJ, Daviglus M, Rich S, Kondos GT. Age and gender distributions of coronary artery calcium detected by electron beam tomography in 35,246 adults. Am J Cardiol 2001;87:1335-1339.
14. Visek WJ. Arginine neds, physiological state and usual diets. A reevaluation. J. Nutr 1986;116:36-46.
15.Wu G, Morris SM. Arginine metabolism:nitric oxide and beyond. Biochem J 1998;336:1-17.
16. Lerman A, Burnett JC, Higano ST, McKinley LJ, Holmes DR. Long-term l-arginine supplementation improves small-vessel coronary endothelial function in humans. Circulation 1998;97:2123-2128.
17. Steer P, Millgard J, Basu S, Lithell H, Vessby B, Berne C, Lind L. Vitamin C, diclophenac, and l-arginine protect endothelium-dependent vasodilation against elevated circulating fatty acid levels in human.s Atherosclerosis 2003;168:65-72.
18. Acute intravenous l-arginine infusion decreases endothelin-1 levels and improves endothelial function in patients with angina pectoris and normal coronary arteriograms: Correlation with asymmetric dimethylarginine levels. Circulation 2003;107:429-436. 19. Cooke JP. Does ADMA cause endothelial dysfunction. Arterioscl Thromb Vasc Biol 2000;20:2032
20. Wascher TC, Graier WF, Dittrich, P, Hussain MA, Bahadori B, Wallner S, Toplak H. Effects of low-dose l-arginine on insulin-mediated vasodilatation and insulin sensitivity. Eur J Clin Investig 1997;27:690-695.
21. Ignarro LJ, Cirino G, Casini A, Napoli C. Nitric oxide as a signaling molecule in the vascular system: an overview. J Cardiovasc Pharmacol 1999;34:879-886.
22. McNamara DB, BediB, Aurora H, Tena L, Ignarro LJ, Kadowitz PJ, Akers DL. L-arginine inhibits balloon catheter-induced intimal hyperplasia. Biochem Biophys Res Commun 1993;193:291-296.
23. Tarry WC, Makhoul RG. L-arginine improves endothelium-dependent vasorelaxation and reduces intimal hyperplasia after balloon angioplasty. Arterioscler Thromb 1994;14:938-943.
24. Hamon M, Vallet B, Bauter C Wernert N, McFadden EP, Lablanche JM, Dupuis B, Bertrand M. Long-term oral administration of L-arginine reduces intimal thickening and enhances neoendothelium-dependent acetylcholine-induced relaxation after arterial injury. Circulation 1994;90:1357-1362.
25. Candipan RC, Wang B, Buitrago R, Tsao PS, Cooke JP. Regression or progression: dependency on vascular nitric oxide. Arterioscler Thromb Vasc Biol 1996;16:44-50.
26. Maxwell AJ, Zapien MP, Pearce GL, MacCallum G, Stone PH. Randomized trial of a medical food for the dietary management of chronic, stable angina. J Am Coll Cardiol 2002;39:37-45.
27. Maxwell AJ, Anderson B, Zapien MP, Cook JP. Endothelial dysfunction in hypercholesterolemia is reversed by a nutritional product designed to enhance nitric oxide activity. Cardiovasc Drugs Ther 2000;14:309-316. |
