Nitric oxide is a molecule that plays a crucial role in vascular disease. It has a number of actions that lead to relaxation of blood vessels, regeneration of the endothelium (the inner lining of arteries), and inhibition of platelet clumping which makes the blood thinner. The role of nitric oxide in vascular disease has been investigated over the past two decades and scientists have discovered that this molecule is involved in many cardiovascular diseases, including atherosclerosis and thickening of the endothelium. In addition, nitric oxide has been used as a therapeutic tool to treat diseases that range from recurrent narrowing of arteries to inhibiting clotting events. Many commonly used medications have their therapeutic actions through the production of nitric oxide.

Impotence and nitric oxide - supplements?
One of the main physiological causes of impotence, or erectile dysfunction, is inability of the blood vessels in the penis to dilate enough to allow blood flow and engorgement. The most important chemical involved in this process is nitric oxide. Arginine, an amino acid available as a supplement, can help make more nitric oxide but the doses required are high and the effects may not last for long. This is also true for citrulline. Fortunately, there are several herbal supplements that can help dilate blood vessels, including ginseng and others less known but more powerful. Passion Rx has a combination of several potent herbal extracts that help dilate blood vessels and improve erectile function, along with libido and sensation.

Ways NO can improve health and prevent disease
Nitric oxide is known as endothelium-derived relaxing factor. It dilates blood vessels, reduces blood pressure and hence can be of benefit in those with angina, heart failure, pulmonary hypertension and erectile dysfunction. In addition, its powerful antioxidant, anti-inflammatory and antithrombotic actions can reduce atherosclerosis. Low levels of NO are characterized by cells in the body aging quicker, oxidative stress, inflammation, endothelial dysfunction, vascular disease, insulin resistance and type 2 diabetes mellitus.

Chemistry
Nitric oxide is formed from the conversion of L-Arginine by an enzyme called nitric oxide synthase. Nitric oxide can act on neurons in the penis causing dilation of the corpus cavernosum. NO is released from nerve endings and endothelial cells and stimulates the activity of guanylate cyclase, leading to an increase in cyclic guanosine-3',5'-monophosphate (cGMP) and, finally, to cavernous smooth muscle relaxation.

There this supplement choline bitartrate supplement that increases acetycholine neurotransmitter in the brain. I have done done bit of research that acetycholine is part of nitric oxide levels increasing blood flow to the muscles. Will choline supplement do that.
   Acetylcholine can improve blood flow by several mechanisms, including activation of endothelial NO synthase and prostaglandin production. However, we are not sure how a choline supplement influences muscle tissue oxigenation.

Ways to increase levels

Cacao or cocoa ingestion
Acute consumption of flavanol-rich cocoa and the reversal of endothelial dysfunction in smokers.
J Am Coll Cardiol. 2005.
Studies suggest that smoking-related vascular disease is caused by impaired nitric oxide synthesis and that diets rich in flavanols can increase bioactive nitric oxide in plasma. The circulating pool of bioactive nitric oxide and endothelium-dependent vasodilation is acutely increased in smokers following the oral ingestion of a flavanol-rich cocoa drink.

Nitric oxide supplement
There are products that claim to be nitric oxide supplements, but I can't see how nitric oxide, a fleeting neurotransmitter, can be made into a supplement. However, if the supplement includes arginine that converts into NO, that's different. Or the supplement may have certain nutrients or herbs that make it more likely for the body to make nitric oxide or to keep NO levels higher once they are made. It would not be accurate to claim a product is a nitric oxide supplement, but it could be accurate to make the claim that substances within the product could enhance nitric oxide production.

Nitric Oxide side effects
One theoretical potential of very high levels of nitric oxide is low blood pressure.

Research studies
Cardiovascular effects of the phytoestrogen genistein.
Curr Med Chem Cardiovascular Hematol Agents. 2004.
Of the several phytoestrogens, genistein in particular has been shown to be the most efficacious in animal models and experimental studies. Genistein in vitro relaxes rat arteries by a nitric oxide dependent mechanism and enhances the dilator response to acetylcholine of atherosclerotic arteries. Genistein supplementation improves endothelial dysfunction induced by oophorectomy in rats and reduces infarct size in an experimental model of myocardial ischaemia-reperfusion injury. Furthermore, genistein in postmenopausal women increases plasma nitric oxide breakdown products, reduces endothelin-1 levels and improves endothelial dependent vasodilation in post-menopausal women. All these findings, taken together, would suggest that this molecule might represent an attractive alternative for cardiovascular protection.

Acetylcholine -induced vasodilation is mediated by nitric oxide and prostaglandins in human skin.
J Appl Physiology. 2005.
Acetylcholine can effect vasodilation by several mechanisms, including activation of endothelial nitric oxide synthase and prostaglandin (PG) production. In human skin, exogenous acetylcholine increases both skin blood flow (SkBF) and bioavailable nitric oxide levels, but the relative increase is much greater in SkBF than nitric oxide. This led us to speculate acetylcholine may dilate cutaneous blood vessels through PGs, as well as nitric oxide. To test this hypothesis, we performed a study in 11 healthy people. We measured SkBF by laser-Doppler flowmetry at four skin sites instrumented for intradermal microdialysis. We conclude that a portion of the vasodilation effected by exogenous acetylcholine in skin is due to nitric oxide; however, a significant portion is also mediated by PGs.

Nitric oxide, human diseases and the herbal products that affect the nitric oxide signalling pathway.
Clin Exp Pharmacol Physiol. 2003.
Nitric oxide is generated constitutively in endothelial cells via sheer stress and blood-borne substances. It is also generated constitutively in neuronal cells and serves as a neurotransmitter and neuromodulator in non-adrenergic, non-cholinergic nerve endings. and can also be formed via enzyme induction in many tissues in the presence of cytokines. Being a free radical with vasodilatory properties, nitric oxide exerts dual effects on tissues and cells in various biological systems. At low concentrations, it can dilate the blood vessels and improve the circulation, but at high concentrations it can cause circulatory shock and induce cell death. Thus, diseases can arise in the presence of the extreme ends of the physiological concentrations. The high level of flavonoids, catechins, tannins and other polyphenolic compounds present in vegetables, fruits, soy, tea and even red wine (from grapes) induce nitric oxide formation from the endothelial cells to improve circulation and some suppress the induction of inducible nitric oxide synthase in inflammation and infection. Many botanical medicinal herbs and drugs derived from these herbs have been shown to have effects on the nitric oxide signalling pathway. For example, the saponins from ginseng, ginsenosides, have been shown to relax blood vessels (probably contributing to the antifatigue and blood pressure-lowering effects of ginseng) and corpus cavernosum (thus, for the treatment of men suffering from erectile dysfunction.

Herbs that help produce or enhance nitric oxide
There are countless herbs and herbal extracts that can help make more nitric oxide or stimulate nitric oxide release within endothelial cells. I have just listed a few and will add more with time.
Apocynum substance
Chrysin herb
Cacao has polyphenols
Ginseng is used for energy and sexual enhancement

Nitric oxide may be called a hormone. Endothelial nitric oxide synthase (eNOS) has an important role in erection.

Questions
Q. I am a bodybuilder that has been taking the supplement Nitric Oxide to help gain muscle mass. I also have a erectile dysfunction. I like to know if Viagra and the supplement NO can be taken together, and what side effect are.
   A. There is no such thing as far as we know of nitric oxide itself in the form of a supplement since it is a gas, and many companies have a ' nitric oxide ' supplement product and each one of them has a different composition or ingredients. Many of these products have arginine. Therefore, we really don't know what is meant by ' the supplement Nitric Oxide. '

Q. I saw you website and thought you may be able to direct me to information re: nitric oxide side effects. My brother was recently taking NO2 from GNC, he has had a severe reaction and was hospitalized due to psychosis. He has no prior history of any type of psychiatric disorder. Is there any research regarding psychiatric side effects of nitric oxide supplement?
   A. There are various products out there that claim to increase nitric oxide levels. A product that is called Nitric Oxide does not necessarily mean it has nitric oxide in it since NO is a gas that cannot be taken as a supplement. Some herbs and nutrients may increase the body's production of nitric oxide. As far as NO2 from GNC, we took a look at the product on the internet, It appears that there is a product NO2 from MRI, it says, :NO2 Black represents a quantum leap in nitric oxide science. First, NO2 Black sets the standard by giving you the purest Arginine-AKG (ArginPure) Delivered with its clinically tested extended-release delivery technology, pHylex9. Second, NO2 Black's revolutionary "NOS-Enhancing" peptide fraction up-regulates nitric oxide synthase (NOS) and increases your nitric oxide levels as much as 950% over baseline arginine derived nitric oxide (ADNO). Third, the NO2 Black formula includes alpha-lipoic acid, designed to boost your insulin sensitivity and nutrient uptake. Simply put, NO2 Black is the most potent nitric oxide generator ever conceived.*
   We have not seen any studies that have evaluated NO2 levels in humans when given this NO2 product. You may wish to ask the manufacturer what studies have been done and published in a reliable medical journal, and also what side effects have been reported.

Q. Though I test in the normal range of testosterone, I have trouble with erections when I need them and am wondering if there is a blood test to determine the level of nitric oxide in a person's system and whether I am in the normal range? Though you mentioned that l-citrulline is not good for getting erections, would it safely increase the level of NO in my system?
   A. Nitric oxide is a transient substance in the bloodstream and there are no easy tests in a doctor's office to determine levels of nitric oxide. A blood test for nitric oxide at one specific time would mean nothing since levels can fluctuate tremendously throughout the day. Citrulline or arginine may raise nitric oxide levels, but their effect is transient. Rather than focusing on nitric oxide levels, consider trying any of a number of sexual enhancing herbs or supplements that work in multiple ways to improve erections.

Q. I ordered Passion Rx. I am taking a small dose of nitric oxide, Ultra Nitric Oxide by Better Health (2 capsules instead of the recommended 6 per day). Should I discontinue the Ultra Nitric Oxide product by Better Health at this time?
   A. As a general rule, we suggest people take a new supplement by itself rather than combining with other pills. Passion Rx is potent by itself and there would be no need to take it with a nitric oxide supplement. In the long run, Passion Rx is used only 2 or 3 days a week and the nitric oxide supplement can be taken on the days Passion Rx is not being used.

Q.  What herbs or herb would give the biggest or best boost to nitric oxide? .. and.. i also read in your site that there are some herbs that work like Viagra in that they inhibit the "enzyme" that keeps nitric oxide from forming. I like that also, because i was not getting that benefit from my arginine formula.
   A. The human sexual response has many aspects to it including vasodilation, hormone release, influence on neurotransmitters such as dopamine, and many other yet uncharted mechanisms. Nitric oxide boosting is only one aspect of the sexual response. Most herbs have multiple mechanisms, not just enhancement of nitric oxide. For a comprehensive sexual enhancement, a formula that has several herbs that work in different ways to increase the overall sexual response often works better than individual herbs. Passion Rx is a great option.

Does the use of nitric oxide supplements help with muscle mass like creatine supplements do?
    I seriously doubt this. Creatine is great as a muscle mass builder.

Thank you for your website advising the public on various nutrition supplements; I refer to it regularly. I have a question about the advisability of taking nitric oxide generating supplements recommended by Dr. Louis J. Ignarro and others. They claim profound improvements in cardiovascular health. The dosage recommended includes a blend of amino acid supplements: L-arginine 4-6 grams, L-citruline 200-1000 mg, Vitamin C 500 mg, Vitamin E 200 iu, Folic Acid B9 400-800 mg, and Alpha lipoic acid 10mg. Your website comments on L arginine and Alpha lipoic acid dosages. It would appear that you would not recommend the daily, sustained dosages for cardiovascular improvement / maintenance as Dr. Louis J. Ignarro and others?
    Different doctors have different opinions on the appropriate dosages of various supplements. I tend to be on the cautious side and suggest using lower dosages in general.

I have just started taking nitric oxide supplement for weight training, overall good health, and erectile problems. I also take blood pressure medicene. is there a problem with taking both?
    There are many types of products that are promoted for nitric oxide enhancement, and many types of medications used for blood pressure. It is not easy to give simple answers.

My father is 90 years old, takes Plavix and has a few stents. He also has gout. If Nitric Oxide is a transition to Nitric Acid, would NO supplements increase his gout attacks?
    There are different nutritional products on the market that claim to increase NO production, and each have a different composition, so it is not easy to say without knowing which product you are referring to. As far as arginine and citrulline, amino acids that are converted into nitric oxide, we have not seen any research that says taking these causes a gout relapse or attack.

I am taking Nitric Oxide Force Factor, I am wondering if this will have an effect on my blood thinner I am taking. I had a knee replacement 1 year ago. I have thrown about 4 blood clots so far this year. But, Since I have been taking Force Factor and have been working out with light to medium weights. I have not had any problem with clots. But the doctors want me to stay on the blood thinners. I take 8 mg of Coumadin a day. I started out taking the Coumadin at 6 mg a day. My reading on the thinner is not good enough for the doctor. I don’t want to get off of the nitric oxide formula. I have felt great. Do you have any suggestions.
    I have not seen any studies with Force Factor and how it interacts with blood thinners.

How do you reduce the nitric oxide levels in the blood?
    This is an interesting question. I am not sure why this would be necessary. Rather than focusing on how to change the levels of a particular chemical in the blood, one should address the underlying health improvements one wishes to occur. I guess eating lots of junk foods and lots of simple carbohydrates could help reduce the levels but why would anyone want to do this?