In a BH4 dependent reaction, Nitric Oxide Synthase (NOS) converts Arginine in to Nitric Oxide, the molecule that resists plaque formation, vasospasm, and abnormal clotting. If you can make and maintain Nitric Oxide then you will not develop cardiovascular disease. If you have cardiovascular disease and if we can successfully reboot your Nitric Oxide system, than we can stabilize your disease. Every maneuver in drug and non-drug cardiovascular medicine that improves patient symptomatic status and outcome works on this system. Every risk factor (or causative factor for cardiovascular disease) compromises Nitric Oxide generation or maintenance. NOS is also involved in ammonia detoxification, a job that distracts it from its Nitric Oxide generating duties and which uses up BH4. Without adequate levels of BH4 Nitric Oxide Synthase will not convert Arginine in to beneficial Nitric Oxide, but rather in to undesirable free radical species such as superoxide or peroxynitrite.
The NOS D298E abnormality codes for a dysfunctional NOS enzyme. It has trouble breaking down ammonia and it has trouble generating Nitric Oxide. NOS (+) individuals are at greater risk for developing all forms of cardiovascular disease, for experiencing adverse events, and for restenosis following balloon angioplasty. A component of “a positive family history of cardiovascular disease” is related to genes coding for high cholesterol, elevated lipoprotein (a), and iron over absorption. The rest likely relates to inherited abnormalities in NOS, ACE, and the other Methyl Cycle genes. If you are NOS (+) we will pay particular attention to maneuvers designed to lower your ammonia burden, and to address risk factors that compromise Nitric Oxide. As the products of a compromised or genetically abnormal NOS system are the free radicals superoxide and peroxynitrite, aggressive antioxidant supplementation makes sense here (while a broad spectrum program of antioxidant supplementation is always wise, we specifically use Vitamin C to neutralize superoxide and 5-methyl folate to neutralize peroxynitrite). I give two separate two hour presentations on Endothelial Dysfunction, which we have on cassette tape (we will likely have a DVD presentation available late next fall). BH4 supplementation has been demonstrated to improve Nitric Oxide generation and endothelial function in individuals with risk factors such as hyperlipidemia, and we presume that it will do the same in individuals with Methyl Cycle abnormalities.
