Who Should Avoid Nitric Oxide? A Comprehensive Guide to Precautions

October 12, 2025 •

4 min read

While nitric oxide plays a vital role in cardiovascular health by regulating blood vessel dilation, certain individuals should avoid it due to specific health risks and contraindications. A 2006 study published in JAMA even noted an increased risk of death and heart complications in heart attack survivors taking L-arginine, a common nitric oxide supplement.

Quick Summary

This guide details the specific health conditions, including heart disease, hypotension, and liver and kidney issues, that can make both supplemental and clinical nitric oxide dangerous. It also covers critical medication interactions and highlights the importance of consulting a doctor before use.

Key Points

Heart Attack Survivors: Avoid L-arginine supplements, as a study found an increased risk of complications in survivors.
Low Blood Pressure: Individuals with hypotension should not take nitric oxide supplements, which can cause a dangerously low drop in blood pressure.
Specific Heart Defects in Newborns: Inhaled nitric oxide (iNO) is contraindicated for neonates with congenital heart diseases involving right-to-left shunting.
Severe Left Ventricular Dysfunction: Inhaled nitric oxide is risky for patients with this condition due to the potential for causing pulmonary edema.
Medication Interactions: Avoid combining nitric oxide with PDE5 inhibitors (ED drugs), nitrates, or certain blood pressure and diabetes medications due to severe hypotensive risk.
Severe Methemoglobinemia: Inhaled nitric oxide is absolutely contraindicated for patients with this severe congenital blood disorder.
Chronic Illnesses: Caution is advised for individuals with liver cirrhosis, kidney disease, or herpes, as NO can worsen these conditions.

Nitric oxide (NO) is a signaling molecule produced naturally in the body that plays a crucial role in vasodilation—the widening of blood vessels—which is essential for maintaining healthy blood flow and regulating blood pressure. It's used therapeutically in two main forms: as dietary supplements, often containing precursors like L-arginine or L-citrulline, and as an inhaled gas administered in a hospital setting for certain respiratory and heart conditions. While beneficial for many, nitric oxide is not safe for everyone and can be dangerous for people with specific medical conditions or those taking certain medications.

Who Should Avoid Nitric Oxide Supplements?

Nitric oxide supplements are widely available and often marketed for athletic performance or cardiovascular health. However, because they are not strictly regulated like prescription medications, it is vital to understand the risks, especially for those with pre-existing health concerns.

Recent Heart Attack Survivors: A significant warning exists for individuals who have recently experienced a heart attack. Research published in JAMA in 2006 found that heart attack survivors taking the nitric oxide supplement precursor L-arginine had a higher risk of adverse outcomes, including death.
Individuals with Low Blood Pressure (Hypotension): As a potent vasodilator, nitric oxide can cause a further, potentially dangerous drop in blood pressure in individuals who already have low blood pressure. This can lead to fainting, dizziness, and other complications.
Liver Disease (Cirrhosis): People with cirrhosis, a condition involving liver scarring, should be cautious with nitric oxide supplements as it could potentially worsen liver function.
Kidney Disease: Individuals with pre-existing kidney disease may face heightened risks, as nitric oxide supplements can potentially aggravate their condition.
Guanidinoacetate Methyltransferase Deficiency: This is a rare genetic disorder affecting the body's metabolism of arginine, a precursor to nitric oxide. Individuals with this condition should not take nitric oxide supplements.
Active Viral Infections (e.g., Herpes): Some medical professionals have expressed concern that nitric oxide supplementation could exacerbate viral infections like herpes.
Pregnancy and Breastfeeding: There is insufficient research to confirm the safety of nitric oxide supplements during pregnancy and breastfeeding. Healthcare providers advise caution and consultation to weigh potential benefits against risks.
Children: Safety and efficacy data for nitric oxide supplements in children are limited. Pediatricians should be consulted before considering any such supplements.

Who Should Avoid Inhaled Nitric Oxide Therapy?

Inhaled nitric oxide (iNO) is a medical treatment primarily used in hospital settings for neonates with persistent pulmonary hypertension and sometimes as a rescue therapy for adults with severe respiratory distress syndrome. Its use is strictly controlled and has absolute contraindications.

Congenital Heart Disease with Right-to-Left Shunt: Neonates dependent on extrapulmonary right-to-left shunting, such as those with hypoplastic left heart syndrome, should not receive iNO. Reducing pulmonary vascular resistance in these cases can cause a life-threatening reversal of the shunt and systemic hypoperfusion.
Severe Left Ventricular Dysfunction: In patients with pre-existing left ventricular dysfunction, iNO can overwhelm a failing heart by increasing blood flow to the lungs, potentially causing pulmonary edema.
Severe Congenital Methemoglobinemia: Inhaled nitric oxide can cause methemoglobinemia, a blood disorder where red blood cells lose their ability to transport oxygen effectively. Severe congenital cases are an absolute contraindication.
Risk of Gas Expansion in Air-filled Cavities: Due to its ability to expand gas in body cavities much faster than nitrogen, iNO is contraindicated in patients with conditions like pneumothorax, pulmonary blebs, or bowel obstruction.

Dangerous Medication Interactions to Avoid

Both supplemental and inhaled nitric oxide can have serious interactions with other medications. It is crucial to inform your doctor about all drugs, including over-the-counter medications and supplements, before starting any form of nitric oxide.

Cardiovascular and ED Medications

Blood Pressure Medications: Taking nitric oxide supplements with antihypertensive drugs can cause an unsafe drop in blood pressure.
Erectile Dysfunction (ED) Medications: The combination of NO supplements with PDE5 inhibitors like sildenafil (Viagra), tadalafil (Cialis), or vardenafil (Levitra) can cause a severe, life-threatening drop in blood pressure.
Nitrates: Combining inhaled nitric oxide with nitrates used for angina can result in a dangerous drop in blood pressure.

Other Interactions

Diabetes Medications: NO supplements can lower blood sugar, potentially amplifying the effects of insulin or other diabetes medications and causing hypoglycemia.
NSAIDs: Nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, may lower endogenous nitric oxide levels, potentially interfering with the desired effects of NO supplementation.
PPIs: Proton pump inhibitors (PPIs) like esomeprazole (Nexium) can also reduce nitric oxide levels, potentially making supplements less effective.

Comparison Table: Nitric Oxide (NO) vs. Nitrous Oxide (N₂O)

It is important to distinguish between nitric oxide (NO) and nitrous oxide (N₂O), as they are different substances with distinct applications and contraindications.


Feature	Nitric Oxide (NO)	Nitrous Oxide (N₂O)
Function	Vasodilator	Sedative, Analgesic, Anesthetic ('Laughing Gas')
Primary Use	Inhaled: Treats pulmonary hypertension in neonates, sometimes rescue therapy in ARDS. Supplements: Promotes cardiovascular health, athletic performance.	Medical/Dental: Short-term sedation and anxiety relief. Recreational: Abused for euphoric effects.
Key Contraindications	Severe left ventricular dysfunction, ductal-dependent congenital heart disease, severe methemoglobinemia.	Severe vitamin B12 deficiency, respiratory conditions, bowel obstruction.
Major Side Effects	Low blood pressure, rebound pulmonary hypertension upon sudden withdrawal, methemoglobinemia.	Vitamin B12 deficiency with chronic use, nausea, sedation, hypotension.
Regulation	Prescription-only inhaled gas (INOmax, Genosyl). Supplements are less regulated.	Regulated medical gas for administration by trained professionals.

Conclusion

Nitric oxide in both its supplemental and inhaled forms offers potential therapeutic benefits, but it also carries significant risks for specific populations. For heart attack survivors, those with certain cardiovascular diseases, and individuals with liver or kidney issues, nitric oxide can pose serious dangers. In a clinical setting, inhaled nitric oxide is contraindicated for neonates with certain congenital heart defects and for patients with other specific conditions. The critical interactions with common medications for blood pressure, ED, and diabetes also highlight the need for extreme caution. Because of these varied risks, consulting a qualified healthcare provider is an essential step for anyone considering nitric oxide, ensuring its use is appropriate and safe for their unique medical profile.

Learn more about L-arginine safety and side effects on Verywell Health

Frequently Asked Questions

Individuals with heart disease, especially those who have previously had a heart attack, should avoid nitric oxide supplements like L-arginine. A 2006 study showed that heart attack survivors taking L-arginine faced a higher risk of adverse outcomes. Always consult a doctor before starting any supplement if you have a heart condition.

Nitric oxide can interact dangerously with medications that also lower blood pressure, including erectile dysfunction drugs (sildenafil, tadalafil), nitrates, and certain blood pressure medications. Combining them can cause a severe drop in blood pressure.

Yes, inhaled nitric oxide is an absolute contraindication for newborns with specific congenital heart diseases, such as those dependent on right-to-left shunting of blood (e.g., hypoplastic left heart syndrome). It can cause a harmful reversal of blood flow.

No, if you already have low blood pressure (hypotension), you should not take nitric oxide supplements. Nitric oxide promotes vasodilation and could cause an even more significant and dangerous drop in your blood pressure.

Yes, there is limited safety research on nitric oxide supplements during pregnancy and breastfeeding. Healthcare providers generally advise against their use unless explicitly recommended after a thorough discussion of risks and benefits.

Yes, people with kidney disease or liver conditions like cirrhosis should use caution with nitric oxide supplements, as these conditions may increase the risk of side effects or potentially worsen the disease.

Inhaled nitric oxide is contraindicated in patients with pneumothorax or other air-filled cavities (like bowel obstruction). Because NO diffuses into these spaces faster than nitrogen, it can cause the air cavity to expand rapidly, compromising patient safety.