Therein lies the rub, as it does with many nutrient molecules that we rely on for optimizing our wellbeing. NO isn’t, however, a nutrient that people take, like a vitamin. It is, after all, a gas, and breathing it at high concentrations will be fatal. * Rather we get our NO chemically bound (but prepared to be released) in the shape of arginine, an amino acid that is a true nutrient champion. For biochemical versatility in the cardiovascular, immunesystem, central nervous, and neuroendocrine systems, no other amino acid may match its broad spectrum of benefits. It is 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. One may, however, safely breathe NO in extremely dilute form, and inhalation NO therapy is used for a variety of serious ailments, such as pulmonary hypertension, acute respiratory failure, reperfusion injury in cardiac ischemia, and also, possibly, sickle cell anemia (see the sidebar). NO News Is Good NewsThe fantastic news about nitric oxide (NO) continues to pile up–and also from some unexpected quarters. Following are three recent examples of benefits that have tumbled out of the arginine cornucopia. Tuberculosis Tuberculosis kills about 1.5 million individuals each year, mainly in Third World countries, where malnutrition, poor sanitation, and inadequate medical care are typical. Lately, Swedish scientists studied 120 young adults (average age 30) in Ethiopia, where the prevalence of TB and HIV is high.1 All the patients had active pulmonary tuberculosis, and approximately half were HIV-positive, which can be both a risk factor and an exacerbating factor for TB. In addition to their routine TB drug therapy, the patients received 1 g/day of either arginine or placebo for 4 weeks. Arginine created no indications of progress, compared with placebo, in the HIV-positive TB patients. The authors said, “The improved clinical outcome observed in HIV–TB+ patients was likely mediated by augmented production of NO induced by increased arginine consumption” They explained that the absence of progress in the HIV-positive patients on the basis of arginine’s being consumed at the site of other (HIV-related) diseases besides the lungs.
The disease causes fever, headache, muscle ache, chills, sweating, and shaking. It kills over 1 million people annually, the majority of them young African children.
This indicated to the researchers who raising NO degrees through arginine supplementation may prove beneficial in the treatment of malaria. (For more info, see page 13 of this matter)
The red blood cells, which are normally smooth and doughnut-shaped (but with no hole), eventually become twisted into a sickle shape that impairs their ability to squeeze through tiny tissues. This can result in pileups of the sickled cells, depriving tissues from the affected regions of critical oxygen. The result will be pain, occasionally severe, which is the hallmark symptom of this disease. Because these abnormal cells die off far faster than normal ones, there is a chronic shortage of red blood cells–anemia. During episodic flare-ups called sickle cell crisesthat can be extremely painful, the blood levels of arginine and NO are found to be abnormally low and are intimately related to the severity of the pain. So researchers at Harvard Medical School chose to try out NO inhalation treatment (80 parts per million in air(with a face mask) for 4 hours to check whether it would provide relief.3 The patients had been 20 youngsters (average age 16, and all of them black). They reported significant pain reduction in comparison to placebo (which was only plain air), reaching a maximum in 3 hours. The researchers concluded that NO may be a feasible therapy for sickle cell crisis and said that “… arginine, which create[s] NO, might have the exact 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 milestone in medical history has been achieved in 1949 by Linus Pauling, who should have received the Nobel Prize in Medicine and Physiology to it.
Far from injuring us, NO–when it is made within the body from arginine–does lots of things to ensure our good health. It helps regulate our blood pressure, to begin with, when it’s synthesized in the vascular endothelium, the layer of smooth cells (called epithelial cells) that line the inside walls of arteries. There it exerts its characteristic vasodilating effect, i.e., it triggers the cellular responses that relax and dilate the vessel walls when required, so as to lower blood pressure and increase blood flow. Men see (and perhaps admire) the consequence of this process every time that they have an erection, and girls gain similarly, even though the result is not so easily observable. It occurs in a variety of tissues and cells, 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 very different roles in human physiology, but at least one thing that they have in common is a tendency to counteract atherogenesis. This is the procedure by which lesions form in our arteries and start to accumulate fatty deposits of plaque, which leads to atherosclerosis. Here nitric oxide takes center stage. Blood Flow Could Harm Your Arteries The creation of atherosclerotic plaque is a really intricate process that is affected by many distinct things. One which appears to be essential is inflammation of the vascular endothelium. That can be brought about in a variety of ways, some of which are only biochemical. However, the physics of blood circulation (called hemodynamics) also plays a part. When blood flows through an artery, surface forces called shear pressure are created at the arterial wall (the endothelium). Analysis of these forces is straightforward once the blood flows easily, but if it becomes disruptive, the analysis is very hard. Turbulence is very likely to happen where the artery departs from a simple, straight tube shape, such as in a bend or in the vicinity of a branch point where the artery splits in 2. In these places, the bloodstream might swirl about forcefully and cause serious shear stress on the arterial wall. (The hemodynamics is not like that of hydrodynamics, by the way, since blood is unlike water in certain fundamental respects; in the jargon of physics, it’s a non-Newtonian fluid, whereas water is just a Newtonian fluid.) When these nutrients were combined, there was a synergistic effect which has been much greater than that of either the antioxidants. The upshot is that shear-stress damage at such websites makes them vulnerable to inflammation than others, and studies have shown that, sure enough, that’s where atherosclerotic plaque is most likely to form. In the inflammatory process, the vascular endothelial cells discharge destructive free radicals and reactive oxygen species, which further damage the cells and cause them to hospitable to plaque deposits. Researchers Try Antioxidants and Arginine A team of researchers in the USA and Italy inquired whether it might be possible to inhibit such damage during the combined use of antioxidants (vitamins E and C) along with arginine.1 Arginine was 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 adverse tendency of monocytes and leukocytes (2 kinds of white blood cells) to adhere to the inflamed epithelial cells. Furthermore, NO inhibits blood-platelet aggregation, which can be desirable because these aggregates (Syndrome) additionally promote plaque formation. And, of course, NO causes vasodilation, which tends to reduce the shear stress by providing the bloodstream more space in which to flow. So how did the researchers create the difficult dimension of shear stress at regions of inflammation? Well, not in human beings, but in lab devices, where human coronary artery cells and aorta cells from hypercholesterolemic mice were exposed to carefully controlled forces and examined under different conditions, the particulars of which are too complex to go into here. The cells were examined independently, in the presence of vitamins C and E, at the presence of arginine, and at the existence of all three chemicals.
The application of shear stress to the cells failed to cause continual harm, resulting in numerous biochemical responses, for instance, desired release of increased amounts of endothelial NOS (to help synthesize more NO). Along with the program of antioxidants along with arginine (providing more NO) blunted the deleterious impacts of the shear stress, particularly when these nutrients were united–there was a synergistic effect that was much larger than that of either the antioxidants alone or arginine alone. * The authors noted that this is in accord with the striking body of evidence that arginine supplementation reduces the signs of coronary heart disease in patients.
With Arginine, There’s Always More In the central nervous system, NO is essential for motion-related learning processes which take place in the cerebellum. There is also evidence that it improves cognitive functions throughout the mind and that it can be crucial for long term potentiation, the mechanism involved in memory. It plays a vital role in bladder function, helping to protect the kidney’s basement membrane (its filtering system) from endothelial degradation, and it is believed to have immune-system-enhancing properties. When its production is raised through supplementation with arginine, it is responsible for an improvement in insulin sensitivity (a decrease in insulin resistance) in diabetics.