Nitric Oxide 101
Our bodies make NO using a group of enzymes called nitric oxide synthase (NOS). There are three types of NOS enzymes that each have important and distinct roles. They are:
- Inducible NOS (iNOS). This enzyme is activated by inflammation as part of an immune response, particularly in cells called macrophages. It is also present in other cells such as neurons and cells at the blood-brain barrier.
- Neuronal NOS (nNOS). This form is abundant in neurons and helps control neuronal functions. Recently it has been shown that this form of the enzyme is also present in many other types of cells such as the endothelium and smooth muscle cells.
- Endothelial NOS (eNOS). This is the main form of the NOS enzyme that is involved in the control of vascular function.
NO wasn't always recognised as an essential molecule for normal physiological functions. In fact, it was a ground-breaking discovery by researchers in 1980s that opened the door for research into the health benefits of NO. In 1987 researchers published an elegant and first of its kind study showing that the factor which was known at the time as "endothelium-derived relaxing factor" was in fact, NO.
That discovery later earned the researchers a Nobel Prize for their discoveries showing "nitric oxide as a signalling molecule in the cardiovascular system".
The Many Roles of NO
NO is a very busy molecule. It is involved in a huge array of physiological functions, as outlined in the diagram below.
The best-characterised role of NO is being a vasodilator, meaning it relaxes the inner muscles of your blood vessels, causing the vessels to widen. In this way, NO increases blood flow, and this brings many benefits. Some well-known medications, such as Viagra for erectile dysfunction and nitro-glycerine for angina, harness the NO pathway to promote blood vessel widening and improve blood flow.
NO and Sports Performance
Having wider blood vessels and optimal blood flow helps increase the delivery of oxygen and nutrients to working muscles during exercise, thus having the potential to enhance exercise performance. Because of this, supplements that boost NO have proven popular among professional athletes and recreational gym-goers alike.
NO-boosting supplements have been shown to improve exercise performance for cyclists, runners, swimmers and even kayakers. NO-boosting supplements are a natural, steroid-free and safe way to give yourself the best chance of smashing your fitness goals!
NO and Erectile Dysfunction
NO-induced vasodilation also plays a crucial role in erections. NO is needed for the muscles of the penis to relax. This relaxation allows chambers inside the penis to fill with blood to allow the penis to become erect. As mentioned earlier in this blog, the "little blue pill" and similar medicines work via the NO pathway.
Erectile dysfunction is caused by impaired formation and action of NO. Thus, replenishment of NO supports healthy sexual function and for many, NO-boosting supplements have enabled a natural approach to supporting intimacy.
NO Declines with Age
When we're young, the production of NO from the endothelium is both efficient and sufficient. As we age, the amount of NO in our tissues declines. Researchers have uncovered that there are multiple pathways at play that ultimately result in a reduced amount of NO:
- Increased breakdown of NO. As we age, there is an increase in a molecule called superoxide. This rapidly transforms NO into a damaging molecule called peroxynitrite.
- Decreased eNOS. The endothelium loses its ability to create NO because there is less of the eNOS enzyme.
- Reduced building blocks to make NO. An increase in a molecule called arginase reduces the building block for NO production (L-arginine), resulting in lower NO production.
The net result in terms of NO levels in aging is rather stark. It has been shown that there is a gradual decline in endothelial function. One group of researchers showed that there was a 50% loss in endothelial function in those over the age of 60. In another study, it was shown that there was a loss of 75% of endothelium-derived NO in 70-80-year-olds compared to young, healthy 20-year-olds.
The research is unequivocal, endothelial function declines progressively with increasing age. In fact, most studies have shown that this impairment becomes evident during the fourth decade of life. What's really fascinating is that endothelium's responsiveness to NO doesn't change with aging, its just the level of NO and the ability to generate NO that declines.
How to Support Healthy NO Levels
You may be wondering what you can do to support healthy levels of NO as you age. Having a healthy lifestyle is an absolute must and this should include:
- Eating vegetables that are high in nitrates such as beetroot, spinach, and celery. When you consume nitrates, your body converts it to nitric oxide, which in turn causes blood vessels to relax and dilate, facilitating healthy blood flow.
- Eating colourful fruit and vegetables that are high in antioxidants.
- Get your blood pumping with at least 30 minutes of medium to high intensity exercise a day. This helps keep your blood vessels in good shape.
- Limit or omit use of mouthwash. Antibacterial mouthwashes destroy mouth bacteria that convert nitrates to NO. Instead, focus on excellent brushing and flossing and cut out sugar that can cause cavities.
- Consider a supplement to boost NO, such as Xtend-Life's latest innovation, VasQFlow. This product contains NO boosting ingredients including Red Spinach Extract which is clinically proven to increase nitrates (a surrogate marker for NO levels). To learn more about the NO-boosting ingredients in VasQFlow, head to our blog "A Natural Approach to Boosting Nitric Oxide".
Containing NO boosting ingredients including Red Spinach Extract which is clinically proven to increase nitrates.Shop now
Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. L J Ignarro, G M Buga, K S Wood, R E Byrns, G Chaudhuri. Proc Natl Acad Sci USA. 1987 Dec;84(24):9265-9.
Arginase Reciprocally Regulates Nitric Oxide Synthase Activity and Contributes to Endothelial Dysfunction in Aging Blood Vessels. Dan E. Berkowitz, Ron White, Dechun Li, Khalid M. Minhas, Amy Cernetich, Soonyul Kim, Sean Burke, Artin A. Shoukas, Daniel Nyhan, Hunter C. Champion, Joshua M. Hare. Circulation. 2003;108:2000–2006.
Age-related reduction of NO availability and oxidative stress in humans. S Taddei, A Virdis, L Ghiadoni, G Salvetti, G Bernini, A Magagna, A Salvetti. Hypertension. 2001 Aug;38(2):274-9.
Effects of age on endothelium-dependent vasodilation of resistance coronary artery by acetylcholine in humans. K Egashira, T Inou, Y Hirooka, H Kai, M Sugimachi, S Suzuki, T Kuga, Y Urabe, A Takeshita. Circulation. 1993 Jul;88(1):77-81.
Red Spinach Extract Increases Ventilatory Threshold during Graded Exercise Testing. Angelique N. Moore, Cody T. Haun, Wesley C. Kephart, Angelia M. Holland, Christopher B. Mobley, David D. Pascoe, Michael D. Roberts, and Jeffrey S. Martin. Sports 2017, 5, 80.
Nitric oxide and geriatrics: Implications in diagnostics and treatment of the elderly. Ashley C Torregrossa, Mayank Aranke, and Nathan S Bryan. J Geriatr Cardiol. 2011 Dec; 8(4): 230–242.
Dr. Amanda Wiggins
Xtend-Life Research Scientist
Dr. Amanda Wiggins works with Xtend-Life as the Chief Research Scientist, where she can use her passion for science, research and nutrition.
I would love to try your ‘VasqFlow’ formula, as I have heart issues, probably due to a missed hemochromatosis diagnosis and chemo and radiation treatment in 2019. My ejection fraction is around 30% and I am taking Entresto to help my heart function. I am also on a blood thinner ( Apixaban) and spironolactone. I know that my potassium levels are being monitored for excess potassium (I think because of the effects of the Entresto), so I wonder if the potassium in the ‘VasqFlow’ might be an issue. I would dearly love to take something natural to assist my poor heart. 🌻I am a lean 71-year-old woman, otherwise in pretty good health. I do a nearly two-mile walk (up and down a steep grade) most days, as well as other daily exercise.🌻 Any suggestions in this matter would be much appreciated. Thank you for any advise you can give. Cheers, 🌻lynn
p.s. I watched, enjoyed and purchased your recent Dr. Talks summit on the heart. I will watch again and try to follow any advice given there.
Also, I lost my son in a motorcycle accident in 2013, which I believe may have contributed to my present health dilemma. Thank you for reading this. ♥️lynn
Lynn Webster April 13 2023