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Why Nitric Oxide Is So Important

by Jeanine Barone  

Until a few decades ago, researchers paid little attention to nitric oxide’s role in the body. It has long been known that we exhale tiny amounts of this chemical compound, and that it’s an air pollutant from cars and factories. But its molecules are so small and have such a short life span (just a few seconds) that scientists didn’t think that nitric oxide did much in the body.

That changed in the 1980s and 1990s, when the significance of nitric oxide as a chemical messenger in all mammals was established. In 1992, the American Association for the Advancement of Science proclaimed it the “molecule of the year.” Nitric oxide’s physiological importance was officially recognized in 1998 when a Nobel Prize was awarded to three scientists who discovered that it’s a key molecule in the cardiovascular system and helps keep blood vessels healthy and regulate blood pressure. Since then, nitric oxide has also been found to be essential in many other bodily systems (such as the immune system and the nervous system, including the brain) and in many chronic conditions and diseases (such as chronic inflammation, erectile dysfunction, and cancer). This has led researchers to focus on nitric oxideas a potential target for medical therapies.

Like many key compounds in the body,nitric oxide can be a double-edged sword. Produced by the body in small amounts where it is needed, it is essential and helps maintain health. But in larger amounts, it can be harmful and damage cells.

How does nitric oxide affect the heart and blood vessels?

Released by the inner layer of cells (endothelium) of blood vessels, nitric oxide relaxes the vessels and keeps them flexible, allowing them to dilate, boosting blood flow, and helping to control blood pressure. Nitric oxide also has anti-inflammatory effects and helps prevent platelets and white blood cells from adhering to the lining of blood vessels, thus reducing the risk of plaque development. As we age, our cells produce less nitric oxide, so blood vessels become less flexible,which contributes to hypertension, inflammation in blood vessels, and atherosclerosis (plaque buildup)—that is, cardiovascular disease. And there’s a vicious cycle: increasing blood pressure, inflammation, and atherosclerosis, in turn,impair the production and action of nitric oxide.

Recent lab research also suggests that nitric oxide is involved in the respiratory cycle by helping red blood cells to release the oxygen they carry to the body’s tissues.

By the way, the drug nitroglycerin helps relieve chest pain by becoming nitric oxide and thus improving flow of blood and oxygen to the heart.Cardioprotective drugs such as statins and ACE inhibitors also increase nitric oxide availability.

What’s the connection between nitric oxide and erectile dysfunction?

Nitric oxide is well known these days because it is the target of drugs like sildenafil (Viagra), which treat erectile dysfunction(ED).Nitric oxide helps relax blood vessels and smooth muscle in the penis, allowing for the increased blood flow needed to initiate and maintain an erection.Interestingly, sildenafil was originally developed to treat angina, though it turned out that it works better for ED. It’s now well known that ED is connected to cardiovascular disease, and reduced nitric oxide may help explain the link. In fact, some research has found that men who have ED as a result of reduced nitric oxide are at increased risk for cardiovascular disease. Currently researchers are experimenting with ways of delivering nitric oxide directly to the penis via application to its skin.

Keep in mind, ED can be caused by other problems than low nitric oxide, so drugs like sildenafil don’t work for all men with ED. Many medical and emotional factors can contribute to ED.

What does nitric oxide do in the brain?

It plays key roles in a variety of neurological processes, including as a neurotransmitter. Both its underproduction and overproduction of nitric oxide may impact memory and cognitive function and be involved in conditions such as depression, Parkinson’s disease, and Alzheimer’s disease. A reduction in nitric oxide production can lessen blood flow to the brain, as well as possibly increase inflammation and oxidative stress, and thus may contribute to cognitive problems. In addition, nitric oxide in the endothelium can modulate a protein that’s a precursor to amyloid (found in plaques that are a hallmark of Alzheimer’s).

How does nitric oxide affect the immune system?

Certain immune cells generate nitric oxide, which is important as a defense molecule against bacteria and other pathogens. It also regulates the activity, growth, and death of many immune and inflammatory cell types.

What is nitric oxide’s role in cancer?

The double-edged nature of nitric oxide is noteworthy when it comes to cancer. For instance, as a signaling molecule, nitric oxide can cause cancer cells to destroy themselves (apoptosis). But it can also promote growth of blood vessels (angiogenesis), which cancer needs in order to grow. Some chemotherapy drugs cause cells to release nitric oxide in order to trigger apoptosis in tumors. Whether nitric oxide has pro- or anti-cancer effects depends on many factors, including its concentration and the type of tumor.

What foods boost nitric oxide?

Vegetables—notably leafy green vegetables and beets—contain nitrate, which can be converted in the body to nitrites and then to nitric oxide. Studies have shown, for instance, that beet juice can help lower elevated blood pressure, which has been attributed to the ability of its nitrates to boost nitric oxide. A recent review in the American Journal of Clinical Nutrition summarized research showing the beneficial effects of nitrate consumption on blood pressure, arterial stiffness, platelet function, and cerebral blood flow.

Many plant foods, including fruits, chocolate, and red wine, also provide polyphenols and other compounds that can increase nitric oxide production in the body via a variety of pathways.Cells use arginine, an amino acid (one of the building blocks of protein), to make nitric oxide. High-protein foods such as nuts, beans, seeds, turkey, seafood, and dairy products supply arginine. A 2016 study in the journal Nutrients found thathigher dietary intake of arginine was strongly linked with higher blood levels of nitrites and nitrates, which are a measure of nitric oxide production.

So, then, are arginine supplements a good idea?

Studies have shown that arginine supplements can boost the body’s nitric oxide production. A few have also suggested that the supplements can improve the function of blood vessels, enhance coronary blood flow, lower blood pressure, and even reduce angina or other symptoms in people with cardiovascular disease.

Ads for arginine supplements often boast that they are based on Nobel Prize-winning research. Though they have to avoid explicit medical claims, they can make vaguer claims such as “supports nitric oxide production and blood flow for the healthy function of the heart, brain and other organs,” “supports healthy blood pressure levels and blood vessel elasticity,” and “helps keep blood vessels toned and flexible.”

But several clinical trials have found that supplemental arginine did not help in treating people with cardiovascular disease and may actually have worsened their condition. For instance, two well-designed studies raised red flags about arginine supplements and the heart. One, a study in the Journal of the American Medical Association in 2006, found that arginine given to heart attack patients dramatically increased deaths. The study had to be halted; researchers warned strongly against using arginine for heart attack patients. And a study in Circulation in 2007 found that arginine supplements did not help people with peripheral artery disease and may even have made matters worse.

Some dietary supplements that claim to improve sexual performance and sex drive also contain arginine because of its effect on nitric oxide—along with other ingredients (most of them dubious and some possibly dangerous). It’s unknown whether supplemental arginine gets to blood vessels in the penis. Indeed, some studies have found little or no improvement compared to a placebo.

In sum, the benefits of arginine supplements are un­certain and their long-term safety unknown. Increased amounts of one isolated amino acid may create imbalances with other amino acids and thus have adverse effects. And increased nitric oxide might be dangerous for people with certain medical conditions.

Should you have your nitric oxide level measured by your doctor or an OTC test kit?

No. Nitric oxide is difficult to assess except in laboratories doing experimental research. Blood or saliva levels of nitrite may reflect nitric oxide bioavailability in the body. But currently there is no valid, reliable test available to the public, according to a paper in Nitric Oxide: Biology and Chemistry in 2016. Saliva test strips on the market that claim to measure nitric oxide are “not likely to accurately assess nitric oxide bioavailability,” according to the authors.

Bottom line: The best way to maintain a healthy nitric oxide level and keep blood vessels healthy is to eat a varied plant-based diet. Exercising regularly also helps enhance nitric oxide generation. This is one way a heart-healthy diet and exercise help improve cardiovascular health and health in general. And here’s another reason not to smoke: Long-term smoking impairs nitric oxide function in the body.

Also see Sex Boosters in a Bottle.