From the Guidelines
Nitric oxide is a crucial signaling molecule that plays a significant role in maintaining cardiovascular health, immune function, and neurotransmission, and its levels can be supported through dietary and lifestyle interventions, such as consuming nitrate-rich foods and engaging in regular aerobic exercise. To support healthy nitric oxide levels, it is recommended to consume a diet rich in nitrate-containing foods like beets, leafy greens (spinach, arugula), and garlic, which can be converted to nitric oxide in the body 1. Regular exercise, particularly aerobic activities for 30 minutes most days of the week, stimulates nitric oxide production in blood vessels. Supplements that may help include L-arginine (3-6g daily), L-citrulline (3-6g daily), and beetroot extract (250-500mg daily), though these should be discussed with a healthcare provider before starting 1.
Key Benefits of Nitric Oxide
- Dilates blood vessels, potentially lowering blood pressure and improving circulation
- Supports immune function
- Enhances exercise performance
- May improve erectile function in men
- Maintains overall vascular health, including regulating endothelial cell proliferation and angiogenesis 1
Importance of Nitric Oxide in Pulmonary Health
Nitric oxide has been shown to have selective and potent pulmonary vasodilator effects, making it a potential therapeutic agent for conditions such as pulmonary arterial hypertension (PAH) 1. Inhaled nitric oxide has been used to treat various conditions, including newborns with PH, children with congenital heart disease, postoperative PH, ARDS, and lung transplantation 1. However, it is essential to note that while inhaled nitric oxide can improve pulmonary physiology, it may not significantly affect mortality 1.
Lifestyle and Dietary Support
The body produces nitric oxide naturally through enzymes that convert L-arginine to nitric oxide, but production can decline with age, making dietary and lifestyle support increasingly important as we get older 1. A diet rich in nitrate-containing foods and regular aerobic exercise can help support healthy nitric oxide levels. Additionally, supplements such as L-arginine and L-citrulline may also be beneficial, but should be discussed with a healthcare provider before starting.
From the FDA Drug Label
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 reports of accidental exposure to nitric oxide for inhalation in hospital staff has been associated with chest discomfort, dizziness, dry throat, dyspnea, and headache. Nitric oxide donor agents such as prilocaine, sodium nitroprusside and nitroglycerine may increase the risk of developing methemoglobinemia. The safety and efficacy of nitric oxide for inhalation has been demonstrated in term and near-term neonates with hypoxic respiratory failure associated with evidence of pulmonary hypertension. Overdosage with INOmax is manifest by elevations in methemoglobin and pulmonary toxicities associated with inspired NO2. Nitric oxide relaxes vascular smooth muscle by binding to the heme moiety of cytosolic guanylate cyclase, activating guanylate cyclase and increasing intracellular levels of cyclic guanosine 3',5'-monophosphate, which then leads to vasodilation.
The effects of nitric oxide on health are primarily related to its use as a pulmonary vasodilator in patients with hypoxic respiratory failure and pulmonary hypertension. The main benefits of nitric oxide include:
- Improved oxygenation in neonates with persistent pulmonary hypertension of the newborn (PPHN)
- Vasodilation of the pulmonary vasculature, which can help to reduce pulmonary vascular resistance and improve blood flow to the lungs However, adverse reactions can occur, including:
- Hypotension
- Methemoglobinemia, which can reduce the oxygen delivery capacity of the circulation
- Pulmonary toxicities associated with inspired NO2, which can cause acute lung injury It is essential to use nitric oxide cautiously and under close medical supervision to minimize the risk of adverse reactions and ensure safe and effective treatment 2.
From the Research
Nitric Oxide and Health
- Nitric oxide (NO) plays a crucial role in various physiological processes, including cardiovascular health and immune response 3, 4, 5, 6, 7
- The nitrate-nitrite-nitric oxide pathway is a potential therapeutic target for patients with pulmonary arterial hypertension (PAH) 3
- Supplementation with nitrate-rich beetroot juice has been shown to increase pulmonary NO production and improve right ventricular function in patients with PAH 3
- Beetroot juice supplementation has also been found to prevent the development of pulmonary hypertension in a rat model, suggesting its potential as a therapy for patients with PH 4
Effects of Nitric Oxide on Cardiovascular Health
- Nitric oxide can have both positive and negative effects on cardiac contractility and the ryanodine receptor, depending on its concentration and the degree of beta-adrenergic stimulation 5
- Acute ingestion of beetroot juice has been shown to increase exhaled nitric oxide in healthy individuals, which may have implications for airway immune response and respiratory health 6
- Nitrate-rich beetroot juice supplementation has been found to reduce blood pressure in both older and younger adults, with greater benefits observed in older adults 7
Age-Related Differences in Response to Nitric Oxide Supplementation
- Older adults may experience greater benefits from nitrate-rich beetroot juice supplementation, including increased plasma nitrite concentrations and reduced diastolic blood pressure 7
- The effects of nitric oxide supplementation on cardiovascular health may vary depending on age, with older adults potentially experiencing greater improvements in cardiovascular function 7