Is Nitric Oxide the Key to Healthy Aging? A Look at Nitric Oxide, Aerobic Capacity, and Strategies to Boost Nitric Oxide Production
There are plenty of high-level athletes performing impressive feats at all ages—the world’s oldest marathon runner completed his last race at age 101! Yet most people experience declines in exercise performance with age and come nowhere near close to running marathons, let alone a few miles, in their older years.
While there are undoubtedly several factors in this reduction in physical capacity, many researchers are pointing the finger at declines in nitric oxide production and bioavailability. Before the 1980s, nitric oxide was thought to simply be a toxic component of air pollution and cigarette smoke. Now, we know that this gas is one of the most critical signaling molecules in the body, affecting everything from cardiovascular to cognitive health.
Researchers are hopeful that strategies to maintain or increase nitric oxide bioavailability may be a valuable way to prevent age-related disorders and preserve the health of the ever-growing population of older adults. In addition to improving health, boosting nitric oxide bioavailability could offset older adults’ declines in exercise and aerobic capacity. So, hopefully, healthy marathon runners in their 80s and beyond will soon be the norm rather than the top news headline.
Nitric Oxide and Aging 101
Nitric oxide is a gaseous signaling molecule essential for the proper flow of blood, nutrients, and oxygen throughout the body.
This nitrogen- and oxygen-containing compound known as a vasodilator relaxes and widens blood vessels to increase blood flow and circulation. These vasodilating properties support cardiovascular, metabolic, cognitive, respiratory, and sexual health, as proper blood flow is vital for maintaining these systems.
There are two known nitric oxide synthesis pathways. First, the compound can be produced endogenously—inside the body—from the amino acid L-arginine, which gets converted into nitric oxide by enzymes called nitric oxide synthases.
The second nitric oxide synthesis pathway is exogenous—meaning, through external sources, like food or supplements. Dietary nitrates first get converted into an intermediate called nitrite, which gets reduced into bioactive nitric oxide in the blood and tissues. While this nitrate-to-nitrite conversion can occur in the stomach, the preferred route is through specific oral bacteria.
Oral dysbiosis, or low amounts of these nitrate-reducing bacteria with higher amounts of unhealthy bacteria, will reduce the amount of available nitric oxide for the body to improve blood flow. Older adults may have reductions in nitric oxide synthesis from this pathway due to age-related differences in the oral microbiome.
In our younger years, the production of nitric oxide through the L-arginine pathway is sufficient. But, as we age, we lose the ability to synthesize nitric oxide in this way efficiently. This age-related decrease in nitric oxide bioavailability, production, and signaling—especially in sedentary older adults—may be a leading reason underlying physiological decline and disease.
In addition to upping your intake of nitrate-rich foods like beets, celery, arugula, and spinach, another way to offset age-related reductions in nitric oxide bioavailability is regular aerobic exercise.
How Nitric Oxide Supports Physical Performance With Age
Aerobic exercise is well-known for improving cardiovascular health. Researchers think this is because the integrity and function of the endothelium—a thin layer of cells lining the blood vessels—are regulated by nitric oxide.
Decreased nitric oxide bioavailability may also impact physical capabilities with age due to reduced skeletal muscle blood flow and function and drops in mitochondrial biogenesis—the growth of new energy-production centers in our cells.
Regular physical activity may preserve or even increase nitric oxide activity with age. In a study published in the Journal of Clinical Biochemistry and Nutrition, researchers looked at the effects of aerobic and resistance exercise training on healthy older adults. After six weeks, the adults who exercised had increased nitric oxide production and decreased arterial stiffness compared to those who didn’t exercise.
A similar study found that older adults who exercised for six weeks saw significant increases in plasma nitric oxide levels during aerobic exercise and reductions in blood pressure during resistance training. These studies suggest that a combination of aerobic and resistance or strength training benefits nitric oxide production and healthy blood pressure.
Other Strategies to Boost Nitric Oxide Naturally
In addition to aerobic exercise, several dietary and supplemental strategies have been shown to augment nitric oxide bioavailability.
Nutritional strategies to boost nitric oxide bioavailability in older adults
L-arginine is an amino acid that gets converted into nitric oxide by nitric oxide synthase enzymes. Therefore, L-arginine supplements or foods high in arginine—meat, poultry, seafood, soy, and nuts—should support a natural increase in nitric oxide.
The amino acid L-citrulline is a direct precursor to L-arginine. Supplementing with L-citrulline might be even more effective at increasing L-arginine levels than L-arginine itself because much of L-arginine is broken down before being absorbed.
Polyphenol-rich foods act as antioxidants to preserve nitric oxide levels. Nitric oxide is particularly sensitive to oxidative damage from free radicals, which increases with age.
Polyphenols are found in red grapes (resveratrol), turmeric (curcumin), green tea (catechins), berries, dark chocolate (anthocyanins), olive oil (hydroxytyrosol), and pomegranate (ellagitannins and gallic acid).
Foods rich in nitrates or nitrites
Food-based nitrates convert into nitrite in the gastrointestinal tract, which then gets reduced into nitric oxide in the blood and tissues.
The most well-known nitrate-rich food is beets and beetroot juice; arugula, turnips, parsley, celery, and spinach are also good sources.
As nitric oxide synthesis and availability are vital for almost every organ, preserving its levels with age could prove critical for maintaining both aerobic capacity and optimal health overall.
Nitric oxide researchers Shannon and colleagues state, “Indeed, given that maximal exercise capacity is strongly associated with reduced risk for age-related morbidity and mortality, identifying novel strategies to boost [nitric oxide] and enhance exercise performance has high biomedical significance. A better understanding of the mechanisms which underpin the reduction in [nitric oxide] bioavailability, and decline in exercise performance, with age, would be valuable and could help with identifying potential targets for future intervention studies.”
Otsuki T, Nakamura F, Zempo-Miyaki A. Nitric Oxide and Decreases in Resistance Exercise Blood Pressure With Aerobic Exercise Training in Older Individuals. Front Physiol. 2019;10:1204. Published 2019 Sep 20. doi:10.3389/fphys.2019.01204
Otsuki T, Namatame H, Yoshikawa T, Zempo-Miyaki A. Combined aerobic and low-intensity resistance exercise training increases basal nitric oxide production and decreases arterial stiffness in healthy older adults. J Clin Biochem Nutr. 2020;66(1):62-66. doi:10.3164/jcbn.19-81
Shannon OM, Clifford T, Seals DR, Craighead DH, Rossman MJ. Nitric oxide, aging and aerobic exercise: Sedentary individuals to Master's athletes. Nitric Oxide. 2022;125-126:31-39. doi:10.1016/j.niox.2022.06.002
Torregrossa AC, Aranke M, Bryan NS. Nitric oxide and geriatrics: Implications in diagnostics and treatment of the elderly. J Geriatr Cardiol. 2011;8(4):230-242. doi:10.3724/SP.J.1263.2011.00230