Nitric Oxide: Benefits and More (2024)

Nitric oxide (NO) is a naturally occurring gas. NO can relax your blood vessels to increase blood flow in your body.

NO supplements, on the other hand, don't have actual NO gas. Instead, the supplements typically contain substances that the body may use and convert to NO. These substances are amino acids—like L-arginine and L-citrulline—and nitrates (NO₃).

Amino acids are the building blocks of proteins, and can be found in food. In your body, L-citrulline is converted into L-arginine before becoming NO. When you take L-citrulline, it doesn't break down by the liver and gut bacteria immediately.

For this reason, L-citrulline might be better absorbed into your bloodstream than L-arginine.

As for nitrates, you can find these substances in certain foods, such as beets and green leafy vegetables.

This article will discuss what you should know about NO supplements—including their potential uses, side effects, interactions, and more.

Uses of Nitric Oxide

While more extensive research is necessary in regard to effectiveness, people use nitric oxide (NO) supplements for various health conditions.

Research is most robust for NO's effects concerning the following:

• Heart health
• High blood pressure in pregnancy
• Erectile dysfunction (ED)
• Athletic performance
  

Heart Health

NO supplements may contain substances—like the L-arginine amino acid. And your body may use and turn L-arginine into NO, which widens blood vessels and improves blood flow.

Due to these effects, NO supplements may support heart health. In fact, a systematic review and meta-analysis (analysis of a collection of studies) showed that L-arginine increased NO levels and blood flow in select groups of people, such as people with heart disease. These effects may also apply to people with excess weight, type 2 diabetes, or both.

These results may support L-arginine's effects on improving blood vessel function in people with heart disease risk. But it's unclear how effective NO supplements—like L-arginine—are because of variability (important differences) between the studies. For example, there were differences in dosage forms, dosages (amounts or strengths), and how long L-arginine worked.

Additional research with higher-quality clinical trials is warranted—especially due to a concern that L-arginine might cause more harm in people with a recent heart attack.

High Blood Pressure in Pregnancy

High blood pressure in pregnancy is a dangerous condition that may negatively affect the parent and unborn fetus.

In an older study, pregnant people had lower blood pressure with long-term use of NO supplements, such as L-arginine. However, conflicting evidence exists for this use.

More research with higher-quality clinical trials is necessary to provide additional data.

Erectile Dysfunction

A review suggested that L-arginine alone or in combination with other medications might help people with erectile dysfunction (ED). The review article also mentioned a study supporting the use of L-citrulline—another NO supplement—in people with mild ED.

But future research with higher-quality and larger studies is still necessary.

Athletic Performance

A review article looked at short-term use of NO supplements—particularly L-citrulline and nitrates. It showed some promise in relaxing blood vessels and improving blood flow to increase muscle performance, size, and strength.

As for L-arginine, there is little evidence to support its use in improving athletic performance.

The evidence for these NO supplements is mixed. However, L-citrulline and nitrates seemed to be the most promising because they are better absorbed into the bloodstream when compared to L-arginine.

But additional research is still warranted, especially longer-term studies.

Nitric Oxide Deficiency

In recent years, there has been a lot of progress toward understanding nitric oxide (NO) and its effects in the human body.

Although additional extensive clinical trials are still necessary, research within the past few decades have shown a possible relationship between NO deficiency and several medical conditions.

What Causes a Nitric Oxide Deficiency?

In general, NO levels might depend on the following:

• Diet: The typical Western diet isn't a rich source of nitrates and nitrites. But eating more fresh vegetables—like from the DASH (Dietary Approaches to Stop Hypertension) diet—will likely increase the amount of nitrates and nitrites in your diet. According to a 2012 review article, a diet with more nitrates lowered the blood pressure of healthy volunteers. But longer-term studies are still warranted.
• Physical inactivity: Physical inactivity may increase heart-related problems. And there is growing evidence that low NO levels might play a role in this. Exercise, on the other hand, may increase NO levels.
• Mitochondrial diseases: Mitochondrial diseases are a group of medical conditions that run through families. In general, these conditions affect your mitochondria. Mitochondria are small components (parts) within your cells that are responsible for making energy. People with mitochondrial diseases have cells that don't make enough energy. People with these conditions may also have low NO levels. This might be because the mitochondria are having trouble making L-citrulline that converts to L-arginine, which eventually turns into NO. People with these conditions may also tend to clear out arginine from the body at a higher rate when compared to the general population.
• Medications: There is a possible relationship between some medications and low NO levels. Examples of these medications include antibiotics (e.g., clindamycin), proton pump inhibitors (PPIs) such as Prilosec (omeprazole), and nonsteroidal anti-inflammatory drugs (NSAIDs) such as Advil or Motrin (ibuprofen) and Aleve (naproxen).
  

How Do I Know if I Have a Nitric Oxide Deficiency?

If you have a nitric oxide (NO) deficiency, you'll experience such short-term symptoms as blood vessel dysfunction and high blood pressure.

In general, a low NO level is likely an early sign that hints at an onset of a chronic (long-term) medical condition.

Long-term or worsening NO deficiency symptoms may include the following:

• Amputation from worsening diabetes (high blood sugar)
• Blindness from diabetes-related eye problems
• Heart disease
• Kidney disease
• Diabetic neuropathy (nerve pain)
• Stroke

What Are the Side Effects of Nitric Oxide?

Nitric oxide (NO) supplements, as with many medications and natural products, may have side effects.

Common Side Effects

Common side effects of NO supplements may include:

• Bloating (gas)
• Diarrhea
• Fast heartbeat
• Headaches
• Heartburn
• Nausea and vomiting
• Stomach pain
  

Severe Side Effects

Severe side effects are possible, especially with large doses of magnesium. Examples of serious side effects include:

• Severe allergic reaction: A severe allergic reaction is a profound side effect possible with any medication or natural product. If you're having a severe allergic reaction, symptoms may include breathing difficulties, itchiness, and rash.
• Heart problems: If you already have a heart condition, NO supplements may worsen it. In particular, L-arginine in people with a recent heart attack might raise the risk of another heart attack, hospitalization (being admitted to the hospital), and death.
• Low blood pressure: NO supplements might lower your blood pressure. If your blood pressure is too low, you might experience dizziness and fainting spells.
• Lung problems: As an inhaled (breathed-in) prescription, nitric oxide's potentially severe side effects may generally include lung and breathing problems.
• Abnormal white blood cell (WBC) count: L-arginine may raise the levels of certain WBCs.

If you're having a severe allergic reaction or if any of your symptoms feel life-threatening, call 911 and get medical help right away.

Precautions

A healthcare provider may advise against using nitric oxide (NO) supplements if any of the following applies to you:

• Severe allergic reaction: Avoid NO supplements if you have a known allergy to them or their ingredients or parts. If you're unsure if it's safe for you, ask a pharmacist, registered dietitian (RD) or registered dietitian nutritionist (RDN), or healthcare provider for more information.
  
• Pregnancy: NO supplements may have the potential use for high blood pressure in pregnancy. But most NO supplement labels are unlikely to target pregnant people. Before taking NO supplements, contact a healthcare provider to discuss the benefits and risks.
• Breastfeeding: Nitric oxide and nitrates are normally present in breast milk. As an inhaled (breathed-in) prescription, using nitric oxide increases NO blood levels of breastfeeding parents—but not NO levels in breast milk. What's more, nitric oxide as an inhaled prescription has been used in newborns to treat respiratory failure, but NO supplements might be safe while breastfeeding. Before taking NO supplements, reach out to a healthcare provider to discuss the benefits and risks.
• Adults over 65: Some older adults tend to be more sensitive to medication side effects, particularly those with a recent heart attack. So, use caution and speak with a healthcare provider before taking NO supplements.
• Children: As an inhaled prescription, nitric oxide has been used in children to treat respiratory failure. And there are a few NO supplements that target children. Since there is limited information about the effects and safety of NO supplements in children, however, talk about the benefits and risks of these supplements with a healthcare provider.
• Abnormal white blood cell (WBC) count: L-arginine may raise your WBC count. So, your healthcare provider may want to closely monitor you and your WBC levels—if you're taking L-arginine.
• Certain digestive system problems: Nitric oxide might play a role in balancing the amount of water and electrolytes (salts) in your intestines (gut). But if there is already an imbalance, you might have a higher likelihood of side effects from NO supplements. So, talk with a healthcare provider about benefits and risks before trying NO supplements.
• Guanidinoacetate methyltransferase deficiency (GAMT): GAMT is a condition that runs in families. People with GAMT don't have a protein to convert arginine into creatine. Therefore, people with GAMT should avoid NO supplements—like arginine.
• Heart conditions: NO supplements may worsen your heart condition, especially a recent heart attack in older adults. So, healthcare providers are unlikely to recommend L-arginine if you have a recent heart attack.
• Low blood pressure: If you have low blood pressure, healthcare providers will likely recommend that you stop NO supplements before going into surgery.

Dosage: How Much Nitric Oxide Should I Take?

Each NO supplement may contain different ingredients in different amounts.

Moreover, further, extensive research with higher-quality clinical trials is warranted to better understand the effects and safety of NO supplements.

For these reasons, there are no guidelines on the appropriate dosage to take NO supplements for any condition.

If you take NO supplements, follow a healthcare provider's suggestions and product label instructions.

What Happens if I Take Too Much Nitric Oxide?

In general, L-arginine and L-citrulline are considered safe.

However, each nitric oxide (NO) supplement might contain different ingredients in various amounts.

So, it's impossible to know the overall safety of all NO supplements.

For this reason, more information about the safety, toxicity, and overdoses of individual NO supplements in humans is needed.

Symptoms of overdoses with NO supplements, however, are likely similar to its potential common and serious side effects—just excessive and more severe.

For example, high NO levels might result in lung injury and methemoglobinemia, which can be life-threatening.

In methemoglobinemia, your red blood cells (RBCs) are having trouble transporting oxygen throughout your body. Symptoms may include:

• Blue skin
• Breathing problems

Interactions

Nitric oxide (NO) supplements might interact with the following:

• Antibiotics: There is a possible relationship between antibiotics and low NO levels. For this reason, antibiotics might work against NO supplements.
• Blood pressure medications: NO supplements—like L-arginine—have lowered blood pressure. So, this may have additive effects with other blood pressure medications, such as Zestril (lisinopril). If your blood pressure is too low, you might experience dizziness and fainting spells.
• Diabetes medications: NO supplements—like L-arginine—have lowered blood sugar. This might have additive effects on your diabetes medications, such as insulin. Symptoms of too-low blood sugar include tremors and sweating.
• Erectile dysfunction (ED) medications: NO supplements have been used for ED. In studies, nitric oxide supplements have lowered blood pressure, similar to several ED medications, such as Viagra (sildenafil). For this reason, taking these medications together might result in excessively low blood pressure. Check with your healthcare provider.
• Inhaled NO prescriptions: In general, the purpose of NO supplements is to increase NO levels. Inhaled NO prescriptions also increases NO levels. As a result, NO supplements might have additive effects with inhaled NO prescriptions. High NO levels may result in lung injury and methemoglobinemia, which can be life-threatening.
• NSAIDs: There is a potential relationship between NSAIDs and low NO levels. So, NSAIDs might work against NO supplements. Advil (ibuprofen) is an example of an NSAID.
• Proton pump inhibitors (PPIs): PPIs—like Nexium (esomeprazole)—might lower NO levels. Therefore, PPIs may work against NO supplements.
  

It is essential to carefully read a supplement's ingredients list and nutrition facts panel to know which ingredients and how much of each ingredient is included. Please review this supplement label with your healthcare provider to discuss potential interactions with foods, other supplements, and medications.

Similar Supplements

In general, nitric oxide (NO) supplements—like L-arginine, L-citrulline, and nitrates—have potential uses for:

• Heart health
• Sexual health
• Athletic performance

Other potentially similar supplements include the following:

• Creatine: With creatine, you may notice an increase in strength, muscle mass, and endurance from vigorous exercise. But creatine also comes with side effects.
• Garlic: Garlic might have beneficial effects on blood pressure and cholesterol, which are risk factors for heart disease.
• Omega-3 fatty acids: Omega-3 fatty acids from fish oil may lower your blood pressure.
• Yohimbe: A potential use of yohimbe is erectile dysfunction (ED), but there is limited research to support this. In the United States, it's also illegal to market over-the-counter (OTC) yohimbe for ED without approval from the Food and Drug Administration (FDA).
  

Only combine multiple natural products after first talking with a healthcare provider, pharmacist, or dietitian. Checking in can help you avoid possible harmful interactions and side effects and ensure you're giving these supplements a fair trial at appropriate doses.

Nutrition

There are several food sources of nitric oxide. Nutrition guidelines typically emphasize food sources of nutrients to improve health.

Food sources of nutrients are preferable to supplements.

However, there is still a place for supplements for certain groups of people, such as those with certain medical conditions.

What Foods Contain Nitric Oxide?

Some foods are rich in nitrates and nitrites. And through your diet, your body may convert the nitrates and nitrites to nitric oxide.

Examples of foods that are good sources of nitrates or nitrites are:

• Beets
• Spinach
• Watermelon

In general, fresh and leafy green vegetables are good options.

Amino acids may also be found in food. For example, foods that contain L-arginine include:

• Dairy products
• Nuts
• Seafood
• Pork
• Red meat
• Watermelon
  

Nitric Oxide Supplements

Nitric oxide (NO) supplements don't actually have the nitric oxide gas.

Instead, NO supplements typically contain substances, such as amino acids—like L-arginine and L-citrulline—and nitrates. And your body may convert these substances into nitric oxide.

In general, NO supplements are likely commonly available as capsules. Other dosage forms of NO supplements include:

• Chewable gummies
• Liquid
• Lozenges
• Powder
• Tablets

But some of these other dosage forms might be in combination with other ingredients.

You may also see vegetarian and vegan options.

What is best for you will depend on form preference and what you hope to get in terms of effects.

Each product may work a bit differently, depending on the form.

Following a healthcare provider's recommendations or label directions is essential.

Other Ways to Increase Nitric Oxide

Aside from diet or supplements, exercise is another way to increase nitric oxide (NO) levels.

Summary

Nitric oxide (NO) supplements contain substances that your body may turn into NO, which is a naturally occurring gas that relaxes blood vessels and increases blood flow.

NO supplements have a few potential uses for:

• Heart health
• Sexual health
• Athletic performance

Since more extensive research is needed, you must ensure the diagnosis and treatment of your medical conditions are completed on time.

Before using NO supplements, ask a registered dietitian, pharmacist, or healthcare provider to weigh in on the process of deciding what may benefit you.