Nitric oxide side effects



The following adverse reactions are discussed elsewhere in the label;

  • Hypoxemia
  • Worsening Heart Failure

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The adverse reaction information from the clinical studies does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates.

Controlled studies have included 325 patients on INOmax doses of 5 to 80 ppm and 251 patients on placebo. Total mortality in the pooled trials was 11% on placebo and 9% on INOmax, a result adequate to exclude INOmax mortality being more than 40% worse than placebo.

In both the NINOS and CINRGI studies, the duration of hospitalization was similar in INOmax and placebo-treated groups.

From all controlled studies, at least 6 months of follow-up is available for 278 patients who received INOmax and 212 patients who received placebo. Among these patients, there was no evidence of an adverse effect of treatment on the need for rehospitalization, special medical services, pulmonary disease, or neurological sequelae.

In the NINOS study, treatment groups were similar with respect to the incidence and severity of intracranial hemorrhage, Grade IV hemorrhage, periventricular leukomalacia, cerebral infarction, seizures requiring anticonvulsant therapy, pulmonary hemorrhage, or gastrointestinal hemorrhage.

In CINRGI, the only adverse reaction (>2% higher incidence on INOmax than on placebo) was hypotension (14% vs. 11%).

Post-Marketing Experience

Post marketing reports of accidental exposure to nitric oxide for inhalation in hospital staff has been associated with chest discomfort, dizziness, dry throat, dyspnea, and headache.

Read the entire FDA prescribing information for Inomax (Nitric Oxide)

  • Many health food stores sell nitric oxide supplements, which claim to boost workout performance and enhance endurance
  • Nitric oxide is a naturally occurring gas in the body that helps increase blood flow
  • Nitric oxide supplements contain ingredients that are said to produce more nitric oxide in the body, thereby improving your workout
  • But do they actually work? The research is mixed

If you spend a lot of time in supplement stores, you’ve probably come across nitric oxide (NO) supplements. And after reading about the amazing benefits they may have for your workout, you may have even been tempted to try them.

For the uninitiated, nitric oxide is a gas produced naturally by the body that helps increase blood flow. NO supplements are said to increase the amount of nitric oxide in your body, which theoretically could lead to enhanced muscle pump, better endurance, and faster recovery. (To be clear, nitric oxide is very different from nitrous oxide, a.k.a. the stuff that gets you high in whip-its.)

In theory, NO supplements could do wonders for your fitness routine. But if these eye-catching claims sound too good to be true, well, you might be right.

What do nitric oxide supplements do?

Nitric oxide is a gas that’s made by your body, and one of its primary purposes is to promote vasodilation, or increased blood flow.

In the body, “nitric oxide is secreted by the endothelial cells, which line the inner walls of the blood vessels, and it communicates with the smooth muscle cells, triggering them to relax,” explains Nathan Jenkins, Ph.D., an assistant professor in the Department of Kinesiology at the University of Georgia. This blood flow regulation plays a role in multiple body functions, including maintaining erections, controlling blood pressure, and more.

NO supplements, however, don’t actually contain nitric oxide — instead, they contain ingredients (or substrates) that are thought to give your body a nudge to produce more nitric oxide, such as L-arginine and L-citrulline.

“Most, if not all, of have not been supported by available evidence.”

“If you’re ingesting nitrate or L-arginine, the idea is that it’s supposed to stimulate the synthesis of nitric oxide in the endothelial cell. So the the more substrates there are, the more NO can be produced,” explains Jenkins.

Because blood is responsible for carrying oxygen to working muscles, the reasoning is that the increased blood flow caused by taking NO supplements might help you work out for a longer period of time and speed up recovery time. Proponents also claim that increased blood flow might increase the “pump’” of your muscles, or how large or pronounced they look (because they’re literally engorged with blood).

OK, but do nitric oxide supplements actually work?

Honestly, we don’t really know. There’s simply not enough evidence to suggest that they do.

” will increase NO, and then because of that, it’ll cause vasodilation, and then the downstream effect of vasodilation would be this massive increase in blood flow, which leads to increased exercise performance and enhanced recovery,” says Richard Bloomer, Ph.D., dean of the School of Health Studies and The Center for Wellness and Fitness at the University of Memphis. “But most, if not all, of have not been supported by available evidence.”

While it is known that L-arginine, L-citrulline, and nitrate play a role in NO synthesis in the body, it’s not known whether taking them in supplement form can also have an impact on NO synthesis. But even if they did increase NO synthesis, it’s unclear whether this would actually make a noticeable difference in exercise performance or recovery.

In studies that have shown a link between improvements in performance and nitrate levels in the blood, such positive results could simply be a result of extensive training, as exercise itself enhances NO activity. Plus, dietary nitrate comes from other sources, like vegetables, and most studies don’t control for this.

Even if there are benefits to NO supplementation, it’s unclear whether they would apply to everyone. A review of 42 studies related to the effects of dietary ingredients linked with NO and exercise performance found mixed results: the review concluded that while NO supplements may “improve tolerance” to aerobic and anaerobic exercise in people who either aren’t in shape or are moderately trained, there seems to be no benefit in highly trained people.

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I read that beetroot juice can improve your workout. Is there any truth to that?

Actually, maybe. A few studies have shown that nitrate supplementation through beetroot juice can be effective at increasing endurance and overall power. One study found a link between 15 days of beetroot juice supplementation and an increase in power max during moderate–intensity cycling tests. While more research is required, both Bloomer and Jenkins note that of the ingredients that may have an impact on NO levels and exercise performance, beetroot juice is the most promising.

Do nitric oxide supplements have any side effects?

Even though the jury’s out on whether NO supplements really do improve performance, Bloomer says if you want to try them at a low dosage, go ahead. That said, if you’re prone to hypotension (or low blood pressure), you might want to skip them, as they could leave you feeling lightheaded or dizzy.

Jenkins also notes that high dosages of NO supplements could put your kidney function at risk, particularly if you already have a nitrate-heavy diet. In such cases, “it might actually cause a reduction in performance, because your kidneys are stressed out and trying to process all this extra nitrate,” says Jenkins. To be on the safe side, don’t take anything more than what’s instructed on the package.

It’s also worth noting that the supplement industry is notorious for its lack of regulation— so if you do really, really want to take them, don’t exceed the suggested dosage, and keep an eye out for any other adverse effects.

Alexa Tucker Alexa is a Denver-based contributor who covers all things lifestyle, wellness, travel, home, and beauty.

What Are Arginine’s Heart Benefits?

In the body, the amino acid arginine changes into nitric oxide (NO). Nitric oxide is a powerful neurotransmitter that helps blood vessels relax and also improves circulation.

Some evidence shows that arginine may help improve blood flow in the arteries of the heart. That may improve symptoms of clogged arteries, chest pain or angina, and coronary artery disease. However, there currently is no data on how the long-term use of arginine affects cholesterol or heart health.

Since arginine may help arteries relax and improve blood flow, it may also help with erectile dysfunction.

There are other potential health benefits with arginine, such as possible reduction of blood pressure in some people and improved walking distance in patients with intermittent leg cramping and weakness known as intermittent claudication. However, the scientific studies are not conclusive enough for experts to make any firm recommendations.

Not all studies on arginine have been positive. A 2006 study showed that arginine was not helpful — and may have been harmful — for treating heart attacks in combination with standard treatment.

Why Nitric Oxide Is So Important

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.

What to know about nitric oxide supplements

This is what the science says about the benefits of taking nitric oxide:

Improves heart health

According to an article published in the journal Biochemical and Biophysical Research Communications, taking nitric oxide supplements offers several heart boosting effects. These include reducing arterial stiffness, reducing blood pressure, and improving carotid artery blood flow. However, it is important to note that the researchers studied animals, not humans, to find these effects.

Enhancing exercise and recovery

Share on PinterestA person may take nitric oxide supplements to improve athletic performance.

Researchers theorize that taking nitric oxide supplements could enhance the delivery of oxygen to muscles. This could potentially improve athletic performance and reduce soreness after a workout.

According to an article in the journal Sports Medicine, studies have shown that taking nitric oxide supplements may enhance tolerance to exercise. However, this only applies to those who did not exercise regularly or only exercised at a moderate rate.

The research has not shown that nitric oxide supplements can help elite athletes. Researchers carried out these studies on young males, so they do not know how nitric oxide supplements may affect older people and females.

Reducing erectile dysfunction

Because nitric oxide supplements enhance blood flow, researchers have conducted studies to determine if it could enhance blood flow for people with erectile dysfunction (ED).

According to an article in the journal Future Science OA, some studies have shown taking nitric oxide may reduce ED in those with mild to moderate ED.

Reducing high blood pressure in pregnancy

Preeclampsia, which is a form of high blood pressure that can occur in pregnancy, can be dangerous for both the woman and baby.

A 2005 study in the European Journal of Clinical Investigation found that pregnant women who took L-arginine supplements for a prolonged period had lower blood pressure readings than pregnant women who did not take L-arginine.

Although researchers need to conduct more studies, the results are promising for women struggling with high blood pressure in pregnancy.

Future research

These are just some examples of more extensive studies that examined the effectiveness of nitric oxide.

However, there are no studies that establish how much nitric oxide supplements people should take to achieve the same results as the study participants did.

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