Picture your body as a bustling metropolis, teeming with diverse activities and processes that must work together to keep the city thriving. In this urban landscape, Nitric Oxide (NO) plays the role of a master city planner, often working behind the scenes yet critical to the smooth operation of the city. It directs traffic flow, ensuring that vital resources reach their destination—our organs and tissues. It also regulates the city’s infrastructure, from ensuring smooth flow in the arterial highways to maintaining clear communication lines in the neural network. With this analogy in mind, let’s now delve into understanding what exactly nitric oxide is, why it is so important, and how we can naturally enhance its production in our bodies.
What Is Nitric Oxide And Why Is It So Vital To Health?
Nitric oxide is a gas and a vital cellular signalling molecule produced by our bodies that control nearly every aspect of our health. Without NO, our cells lack the oxygen and nutrients they need to operate at their best. NO plays a critical role in various functions, including vasodilation (widening of blood vessels), immune response, regulation of inflammation, and neurotransmission. NO was somewhat overlooked until the 1980s when scientists began to uncover its importance in biological functions. The discovery of nitric oxide’s role as a signalling molecule in the body led to a Nobel Prize in Physiology or Medicine in 1998 when Drs. Robert F. Furchgott, Louis J. Ignarro, and Ferid Murad were awarded for their groundbreaking research.(1)
Let’s delve into the extensive roles that nitric oxide plays in our bodies:
Promoting Cardiovascular Health—One of the most well-known functions of nitric oxide is its role in vasodilation. It acts as a signalling molecule in the endothelium, the inner lining of blood vessels, causing the smooth muscles surrounding the vessels to relax. This relaxation results in the dilation of blood vessels, allowing increased blood flow and oxygen delivery to tissues and organs. Insufficient nitric oxide is often linked to conditions like hypertension and heart disease.(2)
Strengthening Immune Function—Nitric oxide serves as an essential component of our body’s innate immune response. It is produced by immune cells, such as macrophages and neutrophils, as part of the body’s defence against pathogens. NO helps in killing bacteria, viruses, and other microorganisms by acting as a cytotoxic agent.
Facilitating Neurotransmission—Nitric oxide functions as a neurotransmitter within our brain, facilitating neuron communication. It is involved in the regulation of various processes, including synaptic plasticity, learning, pain perception, and memory.
Enhancing Athletic Performance—Athletes can greatly benefit from nitric oxide’s role in vasodilation. The increased blood flow facilitated by NO delivers more oxygen and nutrients to muscles. This results in improved endurance and strength, decreased fatigue, and faster recovery post-exercise.
Supporting Erectile Function—Nitric oxide is a key player in male sexual response, particularly in mediating penile erection. Relaxing the smooth muscles in penile blood vessels enhances blood flow and promotes erectile tissue engorgement. Problems with nitric oxide production or signalling pathways can lead to erectile dysfunction.
Promoting Wound Healing—Nitric oxide aids in wound healing by encouraging angiogenesis and the formation of new blood vessels. It also supports the proliferation of cells like fibroblasts and endothelial cells, which are vital for tissue repair. Additionally, NO showcases antimicrobial properties, helping combat infections at the wound site.
Regulating Respiratory Function—In the context of the respiratory system, nitric oxide helps relax the smooth muscles lining our airways, simplifying the process of breathing. In respiratory conditions such as asthma, nitric oxide levels might be disrupted, leading to airway inflammation and narrowing.
Functioning as an Antioxidant—Nitric oxide also acts as an antioxidant, safeguarding cells against oxidative stress and damage inflicted by reactive oxygen species (ROS). It aids in neutralizing harmful free radicals and curtailing excessive ROS production, which can result in cellular dysfunction, DNA damage, and various diseases, including cancer.(3)
Regulating Cellular Signaling—As a versatile signalling molecule, nitric oxide is involved in a multitude of cellular processes. It plays a role in gene expression, cellular metabolism, and cell survival regulation. It interacts with other signalling molecules, like cGMP (cyclic guanosine monophosphate), to orchestrate various physiological responses within the body.
Mitigating Age-Related Decline—Nitric oxide is known to diminish as we age, contributing to various age-associated conditions like cardiovascular disease, cognitive decline, and decreased physical performance. Research has shown that by the time we reach age 40, we produce half or less of the nitric oxide we did at age 20, which continues to decline the older we get. One study found a loss of up to 75% of endothelium-derived NO in 70-80-year-old patients compared to healthy 20-year-olds.(4)
Seeing the many roles of NO in the body, you can understand why maintaining optimal nitric oxide levels is important for mitigating many of these age-related declines. By promoting healthy blood flow, supporting cognitive function, and encouraging muscle health, nitric oxide can help maintain vitality and overall wellness in older adults. Its role in enhancing cellular health and longevity further underscores its significance in aging and age-related health concerns.
How Do We Produce Nitric Oxide?
There are two pathways to produce NO: the arginine to NO pathway and the nitrate to nitrite to NO pathway.(5)
The first is the arginine to NO pathway, also called the enzymatic pathway, is the primary route for the production of nitric oxide in the body. This pathway is mainly responsible for producing NO in endothelial cells lining blood vessels, which is important for regulating vascular tone and blood flow. The arginine to NO pathway involves the conversion of the amino acid arginine to nitric oxide (NO) by nitric oxide synthase (NOS) enzymes.
There are three types of NOS enzymes in humans: endothelial NOS (eNOS), neuronal NOS (nNOS), and inducible NOS (iNOS). Each form is found in different tissues and is responsible for producing nitric oxide under specific conditions. eNOS is found in the endothelial cells lining the blood vessels. It is responsible for the continuous production of NO, which helps regulate vascular tone and blood pressure. eNOS is stimulated by various factors such as shear stress, acetylcholine, and certain hormones. nNOS is found in neurons and skeletal muscle cells and is involved in the regulation of neurotransmission, neuronal development, and immune responses. nNOS produces NO in response to calcium influx into the neuron. iNOS is produced by various cell types, including immune cells, in response to inflammatory stimuli. iNOS generates large amounts of NO over an extended period, contributing to immune responses and defence mechanisms against pathogens. Dysregulation of NOS activity is linked to various diseases, including cardiovascular disease and cancer. Overexpression of iNOS in response to chronic inflammation or other factors can promote DNA damage, genomic instability, and the activation of pro-tumorigenic signalling pathways.
The production of NO through this pathway contributes to vasodilation, regulation of blood pressure, neurotransmission, and other functions related to cardiovascular and neuronal health.
The second, the nitrate to nitrite to NO pathway, also called the non-enzymatic pathway, involves the conversion of dietary nitrates(NO3-) to nitrites (NO2-) by bacteria in the mouth and then to NO in the stomach and circulation. This pathway is important for maintaining NO production in situations where the arginine to NO pathway is compromised, such as in individuals with endothelial dysfunction or low arginine levels.
The nitrate to nitrite to NO pathway occurs when we consume nitrate-rich foods such as leafy green vegetables, beets, and pomegranates. The bacteria in our mouths reduce nitrate to nitrite, which then decomposes to form NO in our acidic stomach.
But wait–aren’t nitrates in food something we should avoid? Nitrates and nitrites occur naturally in many foods and can actually be a part of a healthy diet when consumed in moderation. The real concern arises from the excessive intake of processed foods, as it can lead to elevated levels of nitrates and nitrites in the body. When nitrates or nitrites react with amino acids during the cooking or curing process of processed meats such as bacon, sausage, or hot dogs, they can form nitrosamines. These nitrosamines are known to be carcinogenic and have the potential to increase the risk of cancer.
The main difference between the conversion of nitrates from healthy foods and processed foods lies in the other compounds that are present in the foods. Healthy foods that contain nitrates, such as leafy greens, also contain antioxidants and other beneficial compounds that can help prevent the formation of harmful compounds like nitrosamines. Processed foods, on the other hand, often contain high levels of sodium, saturated fat, and other additives that can increase the risk of disease. In terms of how the body knows the difference, it is primarily based on the presence of other compounds and the overall composition of the food. When nitrates are consumed as part of a healthy, balanced diet, the body is better able to process them in a way that is beneficial.
It’s worth noting that using mouthwash and fluoridated oral hygiene products can negatively affect our mouth bacteria, which can impact the nitrate to nitrite to NO pathway. Therefore, it’s crucial to be mindful of our oral hygiene practices and choose products that support the integrity of our oral microbiome. If you want to learn more about Oral Microbiome, I wrote a blog you can read HERE.
Increase Nitric Oxide Naturally
Given the wide range of NO’s benefits, it’s no surprise that many of us might want to boost its levels. Fortunately, there are several strategies to enhance nitric oxide production in the body:
1. Consume Nitrate-Rich Foods
Due to the standard American diet, which only provides approximately 100-150 milligrams of nitrate per day, many people suffer from nitrate deficiency. This deficiency in the essential molecule can result in various health issues.(6) Diet is one of the easiest ways to naturally increase NO production. Consuming foods high in nitrates, which our body can convert into NO, is beneficial. Vegetables such as beetroot, celery, rhubarb, cabbage, radishes, and dark leafy greens like spinach, chard, kale, and arugula are particularly high in nitrates. Avoid processed and cured meats.
2. Ensure Adequate Stomach Acid
Adequate stomach acid is a crucial component to support the nitrate to nitrite to NO pathway. Here is how you can ensure optimal digestion and assimilation:
- Chew, Chew, Chew—Chewing food thoroughly helps in the mechanical breakdown of food particles and stimulates the production of stomach acid. Take your time to chew your food properly before swallowing.
- Avoid Overeating—Overeating can lead to digestive issues and can disrupt the production of stomach acid. Eat smaller, more frequent meals to ensure optimal digestion.
- Apple Cider Vinegar—Consider adding a tablespoon of raw, unfiltered apple cider vinegar to a glass of water and consuming it before meals. It may help stimulate stomach acid production and improve digestion.
- Digestive Bitters—Incorporate digestive bitters into your routine. These herbal tinctures, containing bitter-tasting plants like dandelion, gentian, and artichoke, can help stimulate stomach acid production naturally.
- Limit Antacid Use–Over-the-counter antacids reduce stomach acid levels, which may interfere with the nitrate-to-nitrite conversion process. Limit the use of antacids unless prescribed by a healthcare professional.
3. Exercise Regularly
Physical activity stimulates NO production as the lining of your arteries releases NO to promote blood flow and supply oxygen to your muscles. Regular aerobic exercises like cycling, walking, jogging, and swimming are particularly beneficial. Research has shown that one hour of aerobic exercise daily for a month increased NO levels, reduced blood pressure, and increased antioxidants in the body.(7)
4. Get Sun Exposure
Exposing your skin to sunlight can stimulate the production of NO. Research suggests that ultraviolet rays can trigger the release of stored NO from the skin into the bloodstream, and the effects can last for days.(8)
5. Limit Alcohol and Tobacco Use
Excessive alcohol and tobacco use can reduce the availability of NO, contributing to endothelial dysfunction, a condition that precedes heart disease. Moderating alcohol and avoiding tobacco can help maintain healthy NO levels.
6. Nasal Breathing
Noses are for breathing; mouths are for eating! The nasal passages contain a rich network of blood vessels and sinuses that produce nitric oxide. As the air flows through the nasal cavity, it comes into contact with these blood vessels, allowing for the absorption of nitric oxide into the bloodstream. By contrast, mouth breathing bypasses the nasal passages, preventing the inhalation of nitric oxide-rich air. Mouth breathing tends to be shallower and less efficient, which can lead to increased respiratory rate and reduced oxygen uptake. This affects the levels of nitric oxide in the body and disrupts the balance between oxygen and carbon dioxide in the bloodstream. Maintaining nasal breathing throughout the day, including during sleep, allows for a more efficient exchange of gases in the respiratory system. This helps to optimize the production and utilization of nitric oxide. To help restore and maintain nasal breathing throughout the night, consider the practice of mouth taping. I recommend and use Myotape.
Supplemental Support for Nitric Oxide Production
There are several supplements and nutraceuticals that are believed to increase nitric oxide (NO) levels in the body.
Beetroot or Beetroot Extract—Beetroot contains high levels of dietary nitrates, which the body can convert into nitric oxide. Consuming beetroot or beetroot extract has been shown to increase nitric oxide levels and improve exercise performance.
Hawthorn Extract—Hawthorn extract is derived from the berries, leaves, and flowers of the hawthorn plant. It has a long history of traditional use in supporting heart health. Hawthorn extract contains various bioactive compounds, including flavonoids and proanthocyanidins, which are believed to contribute to its potential cardiovascular benefits. Some research suggests that hawthorn extract may enhance nitric oxide synthesis, leading to improved blood vessel dilation and blood flow. By promoting better circulation, hawthorn extract may support physical performance and resilience during exercise.
Pycnogenol—Pycnogenol is a patented extract derived from French maritime pine bark. It has been suggested to enhance nitric oxide production by promoting the activity of endothelial nitric oxide synthase (eNOS), an enzyme responsible for nitric oxide synthesis.
Coenzyme Q10 (CoQ10)—CoQ10 is a naturally occurring compound found in the body, which plays a crucial role in energy production. It has been shown to increase nitric oxide production and improve endothelial function.
Aged or Fermented Garlic Extract—Garlic extract can boost nitric oxide levels by activating nitric oxide synthase. One animal study showed a 40 percent increase in nitric oxide levels one hour after garlic consumption.(9)
Antioxidant Vitamins—Vitamins C and E, as well as other antioxidants, can help maintain nitric oxide levels by reducing oxidative stress, which can limit nitric oxide breakdown.
A note on amino acids L-arginine and L-citrulline: L-arginine and L-citrulline have long been recommended for increasing nitric oxide production, however recent research has suggested that supplementing with these amino acids may not be as effective as previously believed, as merely increasing the availability of L-arginine or citrulline may not necessarily translate into higher levels of nitric oxide.(10) Other factors, such as the activity of nitric oxide synthase enzymes, availability of cofactors, and the presence of competing pathways, can influence the overall nitric oxide synthesis process.
Furthermore, the bioavailability and absorption of L-arginine can pose challenges. The metabolism of L-arginine in the liver by the enzyme arginase can limit its conversion to nitric oxide, resulting in a decreased efficacy of supplementation. Citrulline, which is converted to L-arginine in the body, may offer some advantages in terms of bypassing liver metabolism. However, the conversion process might not provide a significant enough increase in L-arginine levels to impact nitric oxide synthesis substantially.
Factors such as age, existing health conditions, genetic differences, and baseline nitric oxide levels can influence the effectiveness of these supplements. Studies show that if you are over 40 or have compromised endothelial function, L-Arginine is unlikely to work for you.(11) It is also important to note that arginine is a potent vasodilator, meaning that it can cause blood vessels to dilate and increase blood flow. While this can be beneficial for some individuals, it can be problematic for those with cardiac or blood pressure concerns, as it may lead to a drop in blood pressure.
As the jury is still out on the benefits, I’d suggest sticking with the other supplements listed above, as science supports their benefits on NO production more clearly.
Several companies offer NO supportive supplements. These supplements aim to increase the production and availability of nitric oxide in the body, primarily by supplying the necessary precursors or promoting the activation of enzymes involved in its synthesis. Some people may experience noticeable effects within a short period, such as minutes or hours after consumption, while others may require longer-term use to observe significant benefits. My personal favourite comes from a company called Berkeley Life. These supplements are specifically designed to enhance nitric oxide production through the nitrate to nitrite to NO pathway mentioned above and help promote cardiovascular health, exercise performance, and blood flow. They offer topical and oral products and convenient nitric oxide saliva test strips, which help assess NO status in as little as 15 seconds. Use my practitioner LINK to see how they can benefit you.
Despite its simplicity, nitric oxide is one of the most crucial molecules in our body, given its numerous functions and widespread impact on health. Adopting lifestyle habits that promote its production can contribute to improved cardiovascular health, better immune function, enhanced cognitive abilities, and improved athletic performance. The understanding of NO is still evolving, and as research continues and we learn more about it, its role in promoting overall health is becoming increasingly apparent. I hope I’ve encouraged you to incorporate strategies to support nitric oxide production in your body–it is truly amazing how such a humble molecule can profoundly influence our well-being!
- “The Nobel Prize in Physiology or Medicine 1998.” NobelPrize.org. Nobel Media AB 2021. Accessed on 2 June 2023. https://www.nobelprize.org/prize/medicine/1998/summary/
- Raddino R, Caretta G, Teli M, Bonadei I, Robba D, Zanini G, Madureri A, Nodari S, Dei Cas L. Nitric oxide and cardiovascular risk factors. Heart Int. 2007;3(1):18. doi: 10.4081/hi.2007.18. Epub 2007 Jun 15. PMID: 21977271; PMCID: PMC3184682.
- Pacher, P., Beckman, J.S., Liaudet, L. (2007). Nitric Oxide and Peroxynitrite in Health and Disease. Physiological Reviews, 87(1), 315-424. doi: 10.1152/physrev.00029.2006
- Torregrossa AC, Aranke M, Bryan NS. Nitric oxide and geriatrics: Implications in diagnostics and treatment of the elderly. J Geriatr Cardiol. 2011 Dec;8(4):230-42. doi: 10.3724/SP.J.1263.2011.00230. PMID: 22783310; PMCID: PMC3390088.
- Lundberg, J. O., Weitzberg, E., & Gladwin, M. T. (2008). “The nitrate–nitrite–nitric oxide pathway in physiology and therapeutics.” Nature reviews Drug discovery, 7(2), 156–167.
- Hord, N.G., Tang, Y., & Bryan, N.S. (2009). “Food sources of nitrates and nitrites: the physiologic context for potential health benefits.” The American journal of clinical nutrition, 90(1), 1-10.
- Tsukiyama Y, Ito T, Nagaoka K, Eguchi E, Ogino K. Effects of exercise training on nitric oxide, blood pressure and antioxidant enzymes. J Clin Biochem Nutr. 2017;60(3):180-186. doi:10.3164/jcbn.16-108
- Hazell G, Khazova M, Cohen H, Felton S, Raj K. Post-exposure persistence of nitric oxide upregulation in skin cells irradiated by UV-A. Sci Rep. 2022;12(1):9465. doi:10.1038/s41598-022-13399-4
- Morihara N, Sumioka I, Moriguchi T, Uda N, Kyo E. Aged garlic extract enhances production of nitric oxide. Life Sci. 2002 Jun 21;71(5):509-17. doi: 10.1016/s0024-3205(02)01706-x. PMID: 12052435.
- Agarwal U, Didelija IC, Yuan Y, Wang X, Marini JC. Supplemental Citrulline Is More Efficient Than Arginine in Increasing Systemic Arginine Availability in Mice. J Nutr. 2017 Apr;147(4):596-602. doi: 10.3945/jn.116.240382. Epub 2017 Feb 8. PMID: 28179487; PMCID: PMC5368575.
- Chen S, Kim W, Henning SM, Carpenter CL, Li Z. Arginine and antioxidant supplement on performance in elderly male cyclists: a randomized controlled trial. J Int Soc Sports Nutr. 2010 Mar 23;7:13. doi: 10.1186/1550-2783-7-13. PMID: 20331847; PMCID: PMC2860344.