Unlocking the Health Benefits of Nitric Oxide: How This Molecule Supports Cardiovascular Health, Exercise Performance, and More

Nitric oxide is a powerful and often overlooked signaling molecule responsible for relaxing the blood vessels and improving blood circulation. Its many physiologic actions in the different body tissues provide many health benefits. Nitric oxide deficiency can, therefore, result in chronic disease and contribute to advanced aging. Dietary and lifestyle habits can impact nitric oxide production in the body. This article will discuss some health benefits of fostering nitric oxide levels and how to do it.

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What is Nitric Oxide?

Nitric oxide (NO) is an essential gaseous signaling molecule made of one nitrogen and one oxygen atom. The discovery in 1998 by three scientists that NO is the endothelial-derived compound responsible for relaxing and dilating arteries won them the Nobel Prize that year, after NO was already named "Molecule of the Year" in 1992.

The body makes NO endogenously by two primary pathways; each contributes about half of the total body NO production. The first pathway occurs by the enzyme Nitric Oxide Synthase (NOS), which converts L-arginine to NO. The second pathway is the Nitrate-Nitrite-NO pathway, in which dietary nitrates are converted into nitrite by oral bacteria and then to NO by various biochemical conversions. (1)

What is Nitric Oxide's Role in the Body?

NO has many roles in the body, the most notorious being its protective role in supporting endothelial function and preventing cardiovascular disease. However, NO's physiologic effects can extend beyond the vascular system, depending on the NOS isoform that is expressed. Three NOS isoforms exist: neuronal NOS (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS). nNOS supports the brain and neuronal communications; eNOS is responsible for vasodilation, glucose uptake, and activation of muscle mitochondrial energy utilization; and iNOS promotes inflammatory reactions and tissue destruction. (2)

Within the vasculature, NO induces vasodilation, inhibits platelet aggregation, prevents platelet adhesion to endothelial cells, inhibits smooth muscle cell proliferation, regulates programmed cell death, and maintains endothelial cell barrier function. NO generated by neurons acts as a signaling neurotransmitter. NO generated by macrophages acts as an antimicrobial agent. Because of this wide range of physiologic actions, NO has been implicated as an integral molecule in the health of the cardiovascular system and as a key regulator in mitochondrial metabolism, muscular performance, glucose control and insulin sensitivity, and antioxidant pathways. (3-5)

Nitric Oxide Health Benefits

Summarized below are just a few benefits conferred by nitric oxide in the body.

Lowers Blood Pressure

Clinical studies have demonstrated poor vasodilation and arterial stiffness in patients with hypertension (high blood pressure). Similarly, research has implicated decreased NO in impaired endothelial function and hypertension. As a potent vasodilator, NO induces arterial vasodilation, improving blood flow and lowering blood pressure. (6, 7)

Regulates Blood Sugar

NO deficiency may play a role in the development of type 2 diabetes. NO regulates insulin signaling and secretion; if NO levels are decreased, insulin resistance, poor glucose uptake by cells, and elevated blood sugar will result. (8-10)

Enhances Physical Performance and Recovery

Because of its regulatory functions in enhancing blood flow, delivering oxygen to muscles, upregulating metabolism, and modulating inflammatory responses, NO is an important molecule in improving athletic performance and reducing delayed-onset muscle soreness. Studies show that NO-precursor L-citrulline boosts endogenous nitric oxide production, and evidence suggests that NO-boosting performance supplements enhance endurance exercise and recovery. (11-13)

Reduces Erectile Dysfunction

Vasculogenic erectile dysfunction (ED) is the most common type of ED caused by vascular blockages and narrowing that impair blood flow to the penis and impair healthy erection. Pharmacologic agents prescribed for ED, including Viagra and Cialis, augment the effect of NO so that more blood flows into the penis to form an erection. Supplements containing NO-boosting ingredients L-arginine, L-citrulline, and French maritime pine bark extract have also all demonstrated efficacy in enhancing sexual function in males with ED. (14)

Supports Wound Healing

Reduced blood supply can significantly impact wound healing; oxygen and nutrients delivered to cellular waste products carried away from the injured area are required for recovery. Nitric oxide plays many roles in wound healing, including the promotion of the initial inflammatory response, cell proliferation, collagen formation, and formation of new blood vessels. Additionally, nitric oxide has antimicrobial properties that prevent infection at the wound site. (15, 16)

Nitric Oxide Side Effects

For most people, taking NO-boosting supplements is safe. Side effects rarely occur, and when they do are usually mild and may include diarrhea, stomach pain, headache, heart palpitations, and nausea.

Because of its hypoglycemic and antihypertensive actions, people on hypoglycemic or antihypertensive medications and supplements may be at higher risk of hypoglycemia and low blood pressure. Symptoms for both can include irregular heart rate, fatigue, changes in appetite, trouble concentrating, and dizziness.

Additionally, patients taking supplements containing arginine should know that arginine can induce herpetic reactivation and breakout lesions because the herpes virus requires arginine to replicate. (17)

It is always advised to speak with a doctor about the safety of a new supplement before you start taking it.

How to Test Nitric Oxide Levels

The presence of muscle/joint pain, cognitive decline, hypertension, insulin resistance, diabetes, Raynaud's, and asthma (among others) could indicate the presence of a NO deficiency. Testing NO levels is done simply through salivary indicator strips, which measure the amount of nitric oxide recirculated through saliva. The indicator strip's color reflects the total bioavailable NO in the system at the time of the test.

How to Increase Nitric Oxide Naturally

Aging, poor diet, oral hygiene, and lack of exercise are all factors that can contribute to declining NO levels. Here are simple tips that can help boost nitric oxide levels naturally.

Diet

Since dietary nitrate can be converted to nitric oxide in the body, eating foods rich in nitrates is an easy way to boost nitric oxide levels naturally. Approximately 80% of dietary nitrates are derived from vegetable consumption, including spinach, broccoli, cabbage, celery, lettuce, beets, and spinach.

Foods rich in nitric oxide precursors L-arginine and L-citrulline can also support endogenous nitric oxide production (18). L-citrulline is heavily concentrated in watermelon; L-arginine is found in most protein-rich foods, like meat, beans, nuts, and dairy.

Exercise

Moderate physical exercise stimulates NO production. One study found that regular exercise performed 30 minutes three days a week for four weeks significantly increases the basal release of endothelium-derived NO. (19)

Oral Hygiene

A healthy oral microbiome and normal stomach acid levels are required for the bacterial conversion of dietary nitrates to NO. Bacterial species of Actinomyces, Corynebacterium, Haemophilus, Kingella, Neisseria, Rothia, and Veillonella are known to express a nitrate reductase enzyme responsible for the conversion of nitrate to nitrite. When swallowed, the nitrites in saliva are then converted to NO in the stomach's acidic environment. Proton pump inhibitors, antacids, and mouthwash can all interrupt this NO conversion pathway. (20)

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Summary

Harnessing the power of nitric oxide can be a formidable tool in addressing many health conditions related to cardiovascular function and inflammation. Eating a nitrate-rich diet, staying physically active, and maintaining a healthy microbiome and gastrointestinal function are all critical in naturally supporting nitric oxide levels. If you think nitric oxide deficiency may contribute to symptoms you're experiencing, talk to a functional medicine doctor about testing and supplemental options that may be right for you.