Therein lies the rub, as it does with lots of nutrient molecules we rely on for maximizing our wellbeing. NO isn’t, however, a nutrient that we take, like a mineral. It’s, after all, a gasoline, and breathing it at high concentrations will be fatal. * Instead , we get our NO chemically bound (although prepared to be published) in the form of arginine, an amino acid that is a true nutrient champion. For biochemical versatility from the cardiovascular, immune, central nervous, and neuroendocrine systems, no other amino acid may match its broad spectrum of benefits. It’s arginine’s role as the direct chemical precursor of NO which makes it of these great scientific curiosity and such great value as a nutritional supplement. An individual can, however, safely breathe NO in extremely dilute form, and inhalation NO therapy is used for a variety of serious conditions, including pulmonary hypertension, severe respiratory failure, reperfusion injury in cardiac ischemia, and also, perhaps, sickle cell anemia (see the sidebar). NO News Is Good NewsThe fantastic news concerning nitric oxide (NO) has been stack up–and from some unexpected quarters. Following are just three recent examples of benefits that have tumbled from the arginine cornucopia.
Tuberculosis kills about 1.5 million people every year, primarily in Third World countries, where malnutrition, inadequate sanitation, and inadequate medical care are common. Recently, Swedish scientists examined 120 young adults (average age 30) in Ethiopia, in which the prevalence of TB and HIV is high.1 All the patients had active pulmonary tuberculosis, and about half were HIV-positive, which is both a risk factor and an exacerbating factor for TB. Besides their regular TB drug therapy, the patients received 1 g/day of arginine or placebo for 4 weeks. Arginine produced no indications of progress, in comparison to placebo, in the HIV-positive TB patients. The HIV-negative TB patients, however, did improve significantly. The authors said, “The increased clinical outcome found in HIV–TB+ patients was likely mediated by augmented production of NO induced by increased arginine consumption” They explained the absence of progress in the HIV-positive patients on the basis of arginine’s being consumed in the site of other (HIV-related) diseases besides the lungs. Malaria Whereas TB is caused by a bacterium and is spread mainly by coughing, malaria is caused by a tiny parasite transmitted by the bite of a female mosquito. It kills over 1 million people annually, the majority of them young African kids.
Once the researchers measured the children’s plasma arginine levels, they discovered a striking inverse correlation with the severity of the children’s state: arginine levels were normal in the controls, so low in those with uncomplicated malaria, and very low in those with cerebral malaria. This suggested to the researchers who raising NO degrees through arginine supplementation may prove beneficial in treating malaria. (For more information, see page 13 of this issue .) Sickle Cell Anemia
The red blood cells, which are normally smooth and doughnut-shaped (but without the hole), become distorted into a sickle shape that impairs their ability to squeeze through tiny capillaries. This may lead to pileups of the sickled cells, depriving tissues in the affected areas of critical oxygen. The result will be pain, occasionally severe, that is the hallmark symptom of the disease. Since these abnormal cells die off far faster than normal ones, there is a chronic lack of red blood cells–anemia. During episodic flare-ups called sickle cell crises, which can be extremely painful, the blood levels of arginine and NO are proven to be abnormally low and are inversely correlated with the severity of the pain. Thus researchers at Harvard Medical School decided to try out NO inhalation therapy (80 parts per million in air(with a face mask) for 4 hours to check whether it would provide relief.3 The patients were 20 youngsters (average age 16, and all them black). They reported significant pain reduction compared with placebo (that was just plain air), reaching a maximum in 3 hours. The researchers concluded that NO may be a feasible treatment for sickle cell crisis and said that “… arginine, which produce[s] NO, might have the same NO-mediated advantages as inhaled NO.” Sickle-cell anemia, by the way, was the first human disorder ever to be clarified at the only molecular level. This wonderful landmark in medical history has been attained in 1949 by Linus Pauling, who should have received the Nobel Prize in Medicine and Physiology to it. References
Far from injuring us, NO–when it is created within the body from arginine–does many things to ensure our great health. It helps regulate our blood pressure, to begin with, when it is synthesized in the vascular endothelium, the layer of cells that are smooth (called epithelial cells) that line the inside walls of arteries. There it consumes its characteristic vasodilating effect, i.e., it triggers the cellular responses that relax and dilate the vessel walls when needed, in order to lower blood pressure and increase circulation. Men see (and maybe admire) the consequence of this process whenever that they have an erection, and women benefit similarly, even though the result is not so easily observable. Arginine’s benefits derive primarily from its ability to release nitric oxide when it undergoes a chemical transformation into the amino acid citrulline; the reaction is catalyzed by the enzyme nitric oxide synthase (NOS). It takes place in many different cells and tissues, most notably the vascular endothelium, but also in many kinds of white blood cells and in blood platelets, the tiny cell-like structures that are responsible for blood clotting, or thrombosis. Growth hormone and nitric oxide play different roles in human physiology, but at least one thing that they have in common is a inclination to counteract atherogenesis. This is the procedure by which lesions form in our arteries and begin to accumulate fatty deposits of plaque, which leads to atherosclerosis. Blood Flow Can Harm Your Arteries The creation of atherosclerotic plaque is a very intricate process that is affected by many distinct things. One that appears to be crucial is inflammation of the vascular endothelium. That can be brought about in various ways, some of which are purely biochemical. But the physics of blood flow (called hemodynamics) also plays a significant part. When blood flows through an artery, surface forces known as shear stress are generated at the arterial wall (the endothelium). Analysis of these forces is straightforward once the blood flows easily, but when it becomes disruptive, the analysis is quite difficult. Turbulence is likely to occur where the artery departs from a simple, straight tubing contour, like at a bend or in the vicinity of a division point where the artery splits in two. In these places, the bloodstream might swirl about forcefully and cause severe shear stress on the arterial wall. (The hemodynamics is not like that of hydrodynamics, incidentally, because blood is unlike water in certain fundamental respects; in the jargon of physics, it is a non-Newtonian fluid, whereas water is a Newtonian fluid.) Whenever these nutrients were united, there was a synergistic effect that was much larger than that of either the antioxidants. The upshot is that shear-stress harm at such websites makes them vulnerable to inflammation than others, and research has proven that, sure enough, that is where atherosclerotic plaque is the most likely to form. Researchers Try Antioxidants and Arginine A team of researchers at the United States and Italy inquired whether it might be possible to inhibit such damage through the combined use of antioxidants (vitamins E and C) along with arginine.1 Arginine has been included, of course, as an external supply of NO, to augment the NO formed naturally in the vascular endothelium. NO is known to inhibit the undesirable tendency of monocytes and leukocytes (two types of white blood cells) to adhere to the inflamed epithelial cells. What’s more, NO inhibits blood-platelet aggregation, which is desirable because these aggregates (clots) also promote plaque formation. And, naturally, NO causes vasodilation, which tends to reduce the shear stress by giving the bloodstream more space in which to flow. So how did the researchers make the difficult dimension of shear stress at areas of inflammation? Well, not in human beings, but also in lab apparatus, in which human coronary artery cells and aorta cells in hypercholesterolemic mice were subjected to carefully controlled forces and examined under different conditions, the particulars of which are too complicated to go into here. The cells were examined alone, in the presence of vitamins E and C, in the presence of arginine, and in the existence of all three compounds.
The application of shear stress to the tissues did cause inflammatory harm, resulting in numerous biochemical reactions, including the desirable release of increased levels of endothelial NOS (to help endothelial more NO). And the application of antioxidants and arginine (providing more NO) blunted the inconsistent effects of the shear stress, particularly when these nutrients were united–there was a synergistic effect which has been considerably larger than that of the antioxidants alone or arginine alone.
With Arginine, There’s Always More At the central nervous system, NO is essential for motion-related learning procedures that happen in the cerebellum. There’s also evidence that it enhances cognitive functions through the brain and it may be crucial for long-term potentiation, the mechanism involved in long-term memory. It plays a very important role in kidney function, helping to protect the kidney’s basement membrane (its filtering system) from endothelial degradation, and it is believed to own immune-system-enhancing properties. When its production is raised through supplementation with arginine, it’s in charge of an improvement in insulin sensitivity (a reduction in insulin resistance) in diabetics.