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Nitric oxide (NO) is a molecule produced naturally in almost every cell of the body that enables:
Bodybuilders to lift more.
Elite endurance athletes to run farther.
Lawyers and stockbrokers to sharpen brain function.
Men from all walks of life to improve their blood pressure, reduce stroke risk, and enhance sexual function.
Essential for cardiovascular health, Nitric Oxide plays a crucial role by relaxing and dilating blood vessels, potentially improving blood flow, lowering blood pressure, and reducing clot formation. Nitric Oxide also serves in the body’s chemical warfare against bacteria, viruses, and emerging tumor cells. The role of Nitric Oxide in health is considered so important that the 1998 Nobel Prize in Medicine was awarded to three scientists (including one of my professors at UCLA) for their discoveries regarding nitric oxide as a signaling molecule in the cardiovascular system.
WHY WE NEED TO SUPPLEMENT NITRIC OXIDE
THE DEMANDS OF ATHLETICS
While the effects of nitric oxide (NO) supplementation on athletic performance are still an area of ongoing research, more than one hundred studies have been conducted involving both endurance athletes and everyday individuals. Recent studies have shown benefits for:
Professional tennis players
Collegiate soccer players
NOTE: The research over the past ten years included recreational and professional athletes of both genders and all ages. Results vary depending on factors such as dosage, duration of supplementation, type of exercise, and individual responses.
THE EFFECTS OF AGING
As we age, our bodies produce less Nitric Oxide. By 50, on average, we produce half as much Nitric Oxide as we did when we were younger. You can still function with half as much Nitric Oxide, but you can’t run as fast, lift as much, or maintain an erection as long.
Nitric oxide (NO) plays a crucial role in regulating blood vessel tone and blood pressure. It acts as a vasodilator, causing blood vessels to relax and widen, leading to lower blood pressure. The studies reveal improvement in muscle power, exercise efficiency, and systolic blood pressure.
SEXUAL HEALTH AND FUNCTION
Nitric oxide (NO) plays a crucial role in the physiology of sexual function, particularly in men.
Blood flow is the most essential factor in achieving an erection. Given the distance from the heart, sexual function is one of the first systems in the body where things go wrong. As circulation becomes less efficient with age, blood flow to the arteries of the penis slows, resulting in less predictable erections. You could view this as a curse or a blessing. Problems in the bedroom are often an early warning sign that the heart and blood vessels are narrowing. Intimacy issues can be devastating, but ED could save your life as an early warning sign of blood vessel blockage damage.
Since Nitric Oxide helps to relax blood vessels, including those in the penis, it can be a factor in blood flow and other physiological processes of achieving and maintaining an erection. As a result, there has been research into the potential effects of nitric oxide supplementation on improving sexual function. Before considering any nitric oxide supplementation for improving sexual function, individuals should consult with healthcare professionals, especially if they have underlying medical conditions or are taking other medications. It’s essential to approach the topic of sexual health with a comprehensive and individualized approach.
HOW YOUR BODY SOURCES NITRIC OXIDE
Two primary pathways serve as the source of Nitric Acid: amino acids (the Citrulline-Arginine pathway) and plant-based foods (the nitrate-nitrite pathway). Both pathways contribute to overall levels of nitric oxide and have distinct sources:
Protein—the Citrulline/Arginine Pathway: The arginine pathway involves the amino acids L-Citrulline and L-Arginine. L-Citrulline is easier to digest and is then converted by the kidneys into L-arginine, which is then converted into nitric oxide by the enzyme nitric oxide synthase (NOS). This pathway is active within endothelial cells lining blood vessels, nerve cells, and immune cells. The arginine pathway is crucial for regulating blood vessel dilation, neurotransmission, immune responses, and other physiological processes.
Vegetables and Fruits—Nitrate-Nitrite-Nitric Oxide: The primary source of nitric oxide through the nitrate-nitrite pathway is nitrates consumed in food. Nitrates are naturally present in vegetables such as leafy greens (for example., spinach, kale, lettuce, and arugula) and intensely colored root vegetables (such as beets). Dietary nitrates are converted into a natural form of nitrite by bacteria in the mouth and stomach acidity.
The nitrate-nitrite pathway provides an alternative source of nitric oxide, particularly in situations where the arginine pathway is limited.
(Note that mouthwash containing fluoride reduces Nitric Oxide levels in the body, raising blood pressure and decreasing circulation. Medications that reduce stomach acid may have a similar potential effect.)
Both pathways are essential to maintaining cardiovascular health, regulating blood pressure, promoting vasodilation, and supporting various physiological functions. The relative contribution of each path to overall nitric oxide levels can vary depending on factors such as diet, health status, and oxygen saturation.
SIGNS OF NITRIC OXIDE DEFICIENCY
While there are no definitive symptoms exclusively linked to nitric oxide deficiency, some potential indicators include:
Poor Blood Circulation can manifest as cold hands and feet or even more severe circulatory issues.
Impaired Exercise Performance includes reduced exercise capacity, fatigue, and slower recovery.
High Blood Pressure: A deficiency could contribute to higher blood pressure levels.
Erectile Dysfunction: A deficiency in nitric oxide could contribute to erectile dysfunction.
Cognitive Impairment: Nitric oxide is vital for neurovascular coupling, ensuring the brain receives adequate blood flow and oxygen during mental activities. A deficiency can potentially impact cognitive function.
Immune System Dysfunction: Nitric oxide plays a role in immune response, helping to combat infections and modulate inflammation. A deficiency compromises the immune system’s ability to function optimally.
Fatigue and Weakness: Inadequate blood flow and oxygen delivery to muscles can lead to feelings of fatigue and weakness.
Poor Wound Healing: Nitric oxide is involved in wound healing, as it helps promote blood flow to the injured area. A deficiency could potentially slow the healing process.
Cardiovascular Issues: Since nitric oxide is related to blood vessel health and function, a deficiency could contribute to cardiovascular problems, such as atherosclerosis and heart disease.
There is currently no standard test for determining nitric oxide status. As a gas molecule with a half-life of 3 to 4 seconds, it circulates too quickly to measure. Testing nitric oxide levels in the body typically involves measuring its metabolites or related compounds. There isn’t a single widely accepted or routine clinical test specifically for nitric oxide levels. Instead, healthcare professionals often assess markers closely associated with nitric oxide production or activity, such as Blood Nitrite and Nitrate Levels, Salivary Nitric Oxide, Endothelial Function Tests, and Plasma Arginine Levels.
BOOSTING NITRIC OXIDE
We can support our nitric oxide production with fresh vegetables, leafy greens, and fruits high in natural nitrates, either raw, cooked, or juiced. About 80% of the nitrates we obtain from food are derived from vegetables. A typical diet provides, on average, at least 5 grams per day of arginine through foods such as:
Tart leafy greens, including chard, kale, beet greens, and spinach
Salad fixings such as lettuces, spring greens, arugula, endive, celery
Vegetables such as beets, radishes, cabbage, Chinese (Napa) cabbage, leeks
Herbs such as cilantro, basil, parsley, dill
Fruits that include rhubarb, watermelon, pomegranates, and pomegranate juice
Arginine is an amino acid found in protein-rich foods:
Nuts and seeds like almonds, pumpkin seeds, walnuts, pine nuts, and sesame seeds
White meats like turkey, pork, and chicken
Soybeans, peanuts, and chickpeas.
NOTE: If you take BCAAs (branch-chain amino acids), although that will contribute to approximately 80% of your amino acid requirements, neither arginine nor citrulline are included in current BCAA formulas, so they omit nitric oxide support.
When choosing a Nitric Oxide (NO) boosting supplement, it’s important to consider:
Ingredients: Look for supplements that contain ingredients known to support nitric oxide production, including L-Citrulline, and dietary nitrates (from beetroot extract or other sources). Your body absorbs L-Citrulline better than L-arginine. Some supplements may also include other supportive nutrients like antioxidants (e.g., vitamin C and Ginseng) that can help protect nitric oxide from degradation.
Dosage: Check the dosage of the active ingredients in the supplement. For example, most research on L-Citrulline is based on 3 grams per day. Choosing a product that provides an effective and appropriate dose based on clinical research is essential.
Formulation: Supplements come in various forms, such as capsules, tablets, powders, or liquids. Choose a form that is convenient for you and easy to incorporate into your routine.
Quality and Purity: Opt for supplements from reputable brands that adhere to good manufacturing practices (GMP) and have undergone third-party testing for quality and purity.
Additional Ingredients: Be cautious of supplements that contain unnecessary fillers, additives, or artificial ingredients. Read the ingredient list carefully. Only take what you need.
Bioactivity: Researchers believe that L-Citrulline has advantages over L-arginine supplementation. It leads to more sustained increases in plasma arginine levels because it bypasses some metabolic processes regulating them. Some research suggests that L-Citrulline supplementation may also have better absorption and bioavailability than L-arginine, potentially making it more effective in boosting nitric oxide levels.
NOTE: This information has been provided courtesy of AFFIRM Science. A supplement like AFFIRM is ideal when your goal is to boost Nitric Oxide levels and support performance. Each tablet contains L-Citrulline, Beet Root Extract, Ginseng, and Muira Puama. AFFIRM utilizes both pathways that produce NO as well as antioxidants. AFFIRM is produced from quality ingredients that adhere to good manufacturing practices.
Dr. Judson Brandeis Judson Brandeis MD is a board-certified urologist who trained at UCLA and currently practices sexual and rejuvenative medicine for men in San Ramon, California. He was a pioneer in Surgical Robotics and was voted Top Urologist in the SF Bay Area (SF Magazine) 2014-2023. Dr. Brandeis wrote The 21st Century Man, which has won five national book awards for non-fiction and men’s health.
Dr. Brandeis has appeared on The Doctors Show and dozens of Podcasts and Webcasts. He performs clinical research in his San Ramon office on penile enhancement, shockwave therapy, PRP, muscle building, and erectile dysfunction. Dr. Brandeis attended Brown University as an undergraduate and Vanderbilt for Medical School. He received a Howard Hughes Medical Institute Research Award for his year of transplantation immunology research at Harvard Medical School. Dr. Brandeis trained in general surgery for two years and urologic surgery for four additional years at the UCLA Departments of Surgery and Urology.
Athletic Performance Studies
Here are a few studies that have explored the effects of nitric oxide-boosting supplements on athletic performance:
Bailey, S.J., Winyard, P., Vanhatalo, A., et al. (2009). Dietary nitrate supplementation reduces the O2 cost of low-intensity exercise and enhances tolerance to high-intensity exercise in humans. Journal of Applied Physiology, 107(4), 1144-1155. This study found that dietary nitrate supplementation in the form of beetroot juice improved endurance during submaximal exercise and increased tolerance to high-intensity exercise. The researchers suggested that these improvements were related to enhanced oxygen utilization and reduced oxygen cost of exercise.
Lansley, K.E., Winyard, P.G., Bailey, S.J., et al. (2011). Acute dietary nitrate supplementation improves cycling time trial performance. Medicine and Science in Sports and Exercise, 43(6), 1125-1131. This study demonstrated that acute nitrate supplementation (again using beetroot juice) improved performance in a 4-km cycling time trial. The researchers attributed the performance enhancement to improved efficiency in energy production and oxygen utilization.
Cermak, N.M., Gibala, M.J., & Van Loon, L.J. (2012). Nitrate supplementation’s improvement of 10-km time-trial performance in trained cyclists. International Journal of Sport Nutrition and Exercise Metabolism, 22(1), 64-71. In this study, nitrate supplementation led to improved 10-km time-trial performance in trained cyclists. The researchers suggested that nitrate supplementation may have increased exercise efficiency and reduced the oxygen cost of submaximal exercise.
Hoon, M.W., Johnson, N.A., Chapman, P.G., & Burke, L.M. (2013). The effect of nitrate supplementation on exercise performance in healthy individuals: a systematic review and meta-analysis. International Journal of Sport Nutrition and Exercise Metabolism, 23(5), 522-532. This meta-analysis reviewed several studies and concluded that nitrate supplementation had a small positive effect on exercise performance, particularly in endurance-based activities.
Research on Blood Pressure Management
Studies that have investigated the effects of nitric oxide-boosting interventions on blood pressure include:
Coggan, A.R., Leibowitz, J.L., Kadkhodayan, A., et al. (2012). Effect of acute dietary nitrate intake on maximal knee extensor speed and power in healthy men and women. Nitric Oxide, 26(3), 178-183. This study examined the acute effects of dietary nitrate supplementation on knee extensor performance and blood pressure in healthy individuals. The researchers found that nitrate supplementation improved muscle power and reduced systolic blood pressure.
Larsen, F.J., Weitzberg, E., Lundberg, J.O., & Ekblom, B. (2007). Effects of dietary nitrate on oxygen cost during exercise. Acta Physiologica, 191(1), 59-66. In this study, dietary nitrate supplementation (through beetroot juice) reduced the oxygen cost of exercise and improved exercise efficiency. While the primary focus was on exercise performance, the observed improvements in oxygen cost could have implications for blood pressure regulation.
Kapil, V., Milsom, A.B., Okorie, M., et al. (2010). Inorganic nitrate supplementation lowers blood pressure in humans: role for nitrite-derived NO. Hypertension, 56(2), 274-281. This study investigated the effects of dietary nitrate supplementation on blood pressure in healthy volunteers. The researchers found that nitrate supplementation led to reductions in both systolic and diastolic blood pressure.
Bondonno, C.P., Liu, A.H., Croft, K.D., et al. (2015). Absence of an effect of high nitrate intake from beetroot juice on blood pressure in treated hypertensive individuals: a randomized controlled trial. The American Journal of Clinical Nutrition, 102(2), 368-375. This randomized controlled trial examined the effects of high nitrate intake from beetroot juice on blood pressure in individuals with treated hypertension. The study did not find a significant effect on blood pressure, suggesting that the impact of nitrate supplementation on blood pressure might be more pronounced in normotensive or mildly hypertensive individuals.
It’s important to note that while these studies suggest potential benefits of nitric oxide-boosting interventions on blood pressure, individual responses can vary, and the mechanisms involved in blood pressure regulation are complex. Moreover, the long-term effects of nitric oxide-boosting interventions on blood pressure and overall health are areas of ongoing research.
Brain Function Research
Studies that have explored the effects of Nitric Oxide on neuro-cognitive function include:
Presley, T.D., Morgan, A.R., Bechtold, E., et al. (2011). Acute effect of a high nitrate diet on brain perfusion in older adults. Nitric Oxide, 24(1), 34-42. This study investigated the acute effects of a high-nitrate diet (through beetroot juice) on brain perfusion in older adults. The researchers observed increased blood flow to certain brain regions, suggesting a potential improvement in cerebral perfusion.
Gilchrist, M., Winyard, P.G., Aizawa, K., et al. (2014). Effect of dietary nitrate on blood pressure, endothelial function, and insulin sensitivity in type 2 diabetes. Free Radical Biology and Medicine, 68, 7-12. This study explored the effects of dietary nitrate on various health parameters, including endothelial function. Improving endothelial function could have potential implications for cognitive health, as healthy blood vessels are important for optimal brain perfusion.
Bond, V., Curry, B.H., Adams, R.G., & Millis, R.M. (2015). Effects of acute dietary nitrate supplementation on aortic blood pressure and aortic augmentation index in older adults. Nitric Oxide, 48, 1-5. This study examined the effects of acute dietary nitrate supplementation on aortic blood pressure and augmentation index in older adults. While the primary focus was on cardiovascular parameters, improvements in blood pressure regulation could indirectly impact cognitive function.
Kelly, J., Fulford, J., Vanhatalo, A., et al. (2013). Effects of short-term dietary nitrate supplementation on blood pressure, O2 uptake kinetics, and muscle and cognitive function in older adults. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 304(2), R73-R83. This study investigated the effects of short-term dietary nitrate supplementation on various parameters, including cognitive function, in older adults. The researchers found improvements in muscle and cognitive function, potentially attributed to improved oxygen kinetics.
Presley, T.D., Duncan, A., Kim, H., et al. (2015). Effects of high-nitrate beverage consumption on cognitive function and blood flow in older adults. Experimental Gerontology, 70, 1-10. In this study, older adults consumed a high-nitrate beverage, and the researchers assessed its effects on cognitive function and blood flow. The results suggested potential improvements in certain aspects of cognitive function and cerebral blood flow.
Sexual Function References
Here are a few studies that have explored this area:
Chen, J., Wollman, Y., Chernichovsky, T., et al. (1999). Effect of oral administration of high-dose nitric oxide donor L-arginine in men with organic erectile dysfunction: results of a double-blind, randomized, placebo-controlled study. BJU International, 83(3), 269-273. This study investigated the effects of oral L-arginine supplementation, a precursor to nitric oxide, on men with erectile dysfunction. The researchers found that L-arginine supplementation resulted in improved erectile function in some participants.
Klotz, T., Mathers, M.J., Braun, M., Bloch, W., & Engelmann, U. (1999). Effectiveness of oral L-arginine in first-line treatment of erectile dysfunction in a controlled crossover study. Urologia Internationalis, 63(4), 220-223. Similar to the previous study, this research explored the effects of L-arginine supplementation on erectile dysfunction. The study indicated that L-arginine supplementation improved erectile function in a subset of participants.
Stanislavov, R., & Nikolova, V. (2003). Treatment of erectile dysfunction with pycnogenol and L-arginine. Journal of Sex & Marital Therapy, 29(3), 207-213. This study examined the effects of a combination of L-arginine and the natural antioxidant supplement pycnogenol on erectile function. The researchers found that the combination therapy improved erectile function in men with mild to moderate erectile dysfunction.
Meldrum, D.R., Gambone, J.C., Morris, M.A., & Ignarro, L.J. (2011). A multifaceted approach to maximize erectile function and vascular health. Fertility and Sterility, 96(3), 685-691. This review article discusses the role of nitric oxide in erectile function and highlights various approaches, including supplementation with L-arginine, to enhance nitric oxide production and improve sexual function.
Araujo, A.B., Travison, T.G., Ganz, P., et al. (2008). Erectile dysfunction and mortality. Journal of Sexual Medicine, 5(6), 1498-1507. While not a direct study of nitric oxide supplementation, this research examined the association between erectile dysfunction and mortality. Erectile dysfunction is often linked to impaired nitric oxide function. The study suggested that the severity of erectile dysfunction may be a predictor of increased mortality risk.
Shirai M., et al. Oral L-citrulline and Transresveratrol Supplementation Improves Erectile Function in Men with Phosphodiesterase 5 Inhibitors: A Randomized, Double-Blind, Placebo-Controlled Crossover Pilot Study. (2018) This is the first study to show that combination therapy of L-citrulline and transresveratrol is effective for ED treatment in men with added on-demand use of PDE5i. This combination supplement may be added if PDE5i is insufficient.
Cormio L., et al. Oral L-citrulline supplementation improves erection hardness in men with mild erectile dysfunction (2011) Although less effective than phosphodiesterase type-5 enzyme inhibitors, at least in the short term, L-citrulline supplementation has been proved to be safe and psychologically well accepted by patients. Its role as an alternative treatment for mild to moderate ED, particularly in patients with a fear of phosphodiesterase type-5 enzyme inhibitors, deserves further research.
It’s important to note that while these studies suggest potential benefits of nitric oxide supplementation for improving sexual function, the results are not always consistent, and individual responses can vary. Additionally, the mechanisms of sexual function are complex, and factors such as overall health, psychological well-being, and hormonal balance also play significant roles.
This is sponsored content. M&F is not endorsing the websites or products listed in this article.