By Eben van Tonder, 28 July 2025
Introduction: The Central Role of Nitric Oxide in Ageing
Among the many physiological processes implicated in ageing, the decline in nitric oxide (NO) production emerges as the most central and wide-reaching factor. Far surpassing other molecular or metabolic deteriorations, the age-related reduction in NO synthesis exerts direct influence over vascular flexibility, cerebral perfusion, mitochondrial efficiency, immune response, sexual function, and muscular oxygenation. It is, without hyperbole, the master regulator of vitality and systemic resilience. While terms like oxidative stress, telomere shortening, or hormonal decline dominate popular discussions on ageing, these are frequently downstream manifestations or amplifiers of nitric oxide deficiency.
Nitric oxide is a gaseous signalling molecule synthesised within the human body primarily through the action of nitric oxide synthase (NOS) enzymes, especially the endothelial isoform (eNOS). It plays a pivotal role in maintaining vasodilation, modulating neurotransmission, facilitating mitochondrial respiration, and regulating immune function. In healthy young individuals, NO is produced continuously through enzymatic conversion of L-arginine to NO and L-citrulline, in a reaction requiring oxygen and several cofactors, including tetrahydrobiopterin (BH₄). However, by the age of fifty, basal NO output is often reduced by 40 to 50 percent, driven by declining eNOS activity, increased oxidative stress, and cumulative vascular endothelial damage (Lauer et al., 2001; Green et al., 1982).
This decline is not simply a passive consequence of time but a reversible, modifiable feature of biological ageing. Numerous interventions, natural, behavioural, and nutritional, have been shown to restore NO production or preserve its bioavailability. This article provides an exhaustive overview of the three most effective and accessible strategies to address this deficiency in older adults: physical exercise, sleep quality, and dietary nitrate intake. Within the dietary category, a particular focus is given to the use of beetroot juice as a nitrate donor and its integration into cured meat products such as bacon. By viewing NO through the lens of physiology, nutrition, and lifestyle, we aim to construct a comprehensive, science-grounded roadmap for restoring the biochemical foundation of youth.
Exercise as a Catalyst for Endogenous Nitric Oxide Synthesis
Of all interventions available to ageing individuals, exercise remains the most powerful and well-documented stimulus for nitric oxide production. The physiological mechanism centres on haemodynamic shear stress: during sustained physical exertion, blood flow increases across the vascular endothelium, applying a mechanical force that activates eNOS and stimulates NO synthesis (Kingwell, 2000). This results in vasodilation, enhanced nutrient delivery, improved muscular oxygen uptake, and better thermoregulation. In fact, acute bouts of aerobic exercise can increase NO output by a factor of three to five above resting levels (Lundberg and Weitzberg, 2010).
Crucially, exercise does not merely trigger transient spikes in NO availability. When practised consistently, especially in the form of moderate-intensity aerobic activity such as brisk walking, cycling, or swimming, it upregulates the expression of eNOS and improves the bioavailability of key cofactors, including BH₄. This results in sustained increases in baseline NO production, even during periods of rest. Additionally, long-term training reduces oxidative stress and inflammation, which are key inhibitors of NO signalling (Green et al., 1982; Hord et al., 2009).
These benefits are amplified in ageing populations. As individuals move into their fifth and sixth decades, endothelial function becomes increasingly compromised, often due to sedentary lifestyle, subclinical inflammation, and metabolic disease. Regular cardiovascular exercise offers a targeted physiological reversal of this trajectory. It is especially effective in older adults who have experienced endothelial stiffening and reduced vasodilatory response, as it both improves vascular compliance and re-sensitises the endothelium to shear stress. From a nitric oxide perspective, exercise constitutes not only the most effective stimulant but also the most restorative therapy for reversing age-related vascular decline.
Sleep and the Nocturnal Preservation of Nitric Oxide
While less dramatic than the impact of exercise, sleep plays a vital and often underappreciated role in maintaining nitric oxide bioavailability. Physiologically, deep sleep stages—particularly slow-wave sleep—are associated with reduced sympathetic activity, lower blood pressure, and active restoration of vascular tone. These changes occur, in part, through the reactivation of eNOS and the attenuation of oxidative degradation of NO molecules during the night.
Melatonin, the endogenous hormone that regulates circadian rhythm, is also involved in the nocturnal modulation of nitric oxide. It has been shown to stimulate NO release in various vascular beds and acts synergistically with eNOS to support vasodilation (Lundberg et al., 2008). In healthy sleepers, NO levels naturally rise during the first half of the night and play a role in mediating the physiological dip in nocturnal blood pressure, a phenomenon known to predict cardiovascular risk when absent.
Conversely, sleep deprivation, insomnia, and sleep-disordered breathing, such as obstructive sleep apnoea, have been linked to reductions in NO availability. This is thought to occur due to increased oxidative stress, elevated circulating catecholamines, and disruption of circadian regulation of vascular tone. In ageing individuals—where eNOS activity is already compromised—poor sleep can rapidly exacerbate vascular rigidity, hypertension, and cognitive dysfunction through chronic NO suppression.
The importance of sleep to nitric oxide homeostasis cannot be overstated. While it does not produce large quantities of NO in isolation, it preserves and regenerates the enzymatic systems responsible for its production during waking hours. Aged individuals seeking to maintain optimal NO levels must therefore treat sleep not merely as recovery but as an essential metabolic and endothelial process in its own right.
Dietary Nitrate as an Alternative NO Source: From Beetroot Juice to Cured Meats
In addition to the eNOS pathway, the human body possesses a parallel mechanism for nitric oxide synthesis that becomes especially important with age: the nitrate–nitrite–NO pathway. Unlike the oxygen-dependent eNOS route, this pathway operates via dietary intake of inorganic nitrate, primarily from vegetables such as beetroot, spinach, and rocket. Once consumed, nitrate is absorbed, circulated to the salivary glands, and converted to nitrite by commensal oral bacteria. Upon swallowing, nitrite is further reduced to nitric oxide in the acidic environment of the stomach or through enzymatic pathways in hypoxic tissues (Lundberg et al., 2008; Kapil et al., 2010).
Beetroot juice, in particular, is one of the richest natural sources of dietary nitrate, with concentrations ranging from 250 to 400 mg per 100 ml. Numerous studies have demonstrated that supplementation with 300 to 400 mg of nitrate per day can lower blood pressure, improve endothelial function, and increase exercise performance in both young and older adults (Larsen et al., 2006; Kapil et al., 2010). Importantly, this route of NO production does not depend on oxygen or eNOS, making it especially valuable in ageing individuals with compromised endothelial function.
A novel application of this principle is the infusion of beetroot juice into cured meat products, such as bacon and ham. Standard cured bacon typically contains around 100 ppm of sodium nitrite, which provides roughly 6 mg of nitrite per 60 g serving. While this contributes modestly to NO levels, its impact is limited unless consumed in large quantities. By contrast, adding beetroot juice at a 10 to 13 percent inclusion rate delivers 300 to 400 mg of nitrate per kilogram of product—equivalent to a clinically significant dose. A consumer ingesting 150 to 200 grams of such bacon would receive 45 to 80 mg of dietary nitrate, contributing measurably to systemic NO availability.
Even at a reduced inclusion level of 3 percent, beetroot-infused bacon can deliver approximately 90 mg nitrate per kilogram. Although this falls below the threshold for acute therapeutic effects, it still exceeds the NO contribution of standard cured meats and offers additive benefits, particularly when consumed alongside exercise or other nitrate-rich foods. This approach transforms bacon from a conventional cured product into a functional food with vascular health applications.
It is important to note, however, that nitrate efficacy depends on the presence of a healthy oral microbiome and an acidic gastric environment. Antiseptic mouthwash use, proton pump inhibitors, and poor gut health can all interfere with the conversion process. Therefore, dietary nitrate should be viewed not only as a biochemical substrate but as part of a broader ecological and digestive system that must be supported to ensure optimal NO yield.
Order of Magnitude Comparison: Quantifying NO Contributions
To fully contextualise the effectiveness of each strategy, it is important to attach order-of-magnitude estimates to the actual nitric oxide contribution they produce in the human body. This allows us to compare not just mechanism, but real-world impact.
The human body in a healthy young state produces approximately 0.5 to 1 millimole of nitric oxide per day, equivalent to about 23 to 46 mg of NO gas. This production drops significantly with age, often by nearly half by the age of fifty. The goal of any intervention is to restore or supplement this baseline level.
A 30- to 45-minute cardiovascular workout can increase NO production three to five times above resting levels, meaning a single workout may generate an additional 50 to 100 mg of nitric oxide over a 24-hour cycle, depending on intensity and fitness level. Over time, regular exercise also raises resting NO output, providing a lasting increase.
A full night of restorative sleep does not stimulate large spikes in NO, but it preserves eNOS activity and allows for enzymatic repair. This has been estimated to support the retention of 3 to 6 mg of nitric oxide that would otherwise be lost due to degradation or uncoupling. While modest in numerical terms, this contribution is continuous and cumulative.
Dietary intake of nitrate from beetroot is highly dose-dependent. A serving of 150 to 200 g of bacon infused with 10 to 13 percent beetroot juice can deliver 45 to 80 mg of nitrate, which may yield 5 to 15 mg of nitric oxide depending on conversion efficiency and individual oral flora. At 3 percent inclusion, this falls to around 13 to 18 mg nitrate, or roughly 2 to 4 mg NO—still significant, but closer to the contribution of a single night of good sleep.
Standard bacon with 100 ppm sodium nitrite provides about 6 mg nitrite per 60 g serving. With an assumed 10 percent bioavailability, this yields less than 1 mg of nitric oxide, rendering it a minor contributor unless consumed in large amounts.
When ranked by absolute physiological contribution, exercise clearly delivers the largest return in terms of NO output, followed by sleep, beetroot-enhanced bacon, and finally standard cured meat. This comparison reinforces that while dietary interventions are valuable, especially when intelligently formulated, exercise and sleep form the irreplaceable foundation of nitric oxide support in ageing individuals.
Conclusion: Integrating Lifestyle and Nutritional Strategies to Restore NO
Nitric oxide represents a molecular foundation upon which health, vitality, and resilience are constructed. Its decline with age is not merely a marker of ageing—it is the engine driving it. From impaired blood flow and mitochondrial dysfunction to neurodegeneration and fatigue, the symptoms of NO deficiency cut across all domains of physiological function.
Fortunately, this decline is not irreversible. Through targeted interventions, older adults can restore both the production and bioavailability of nitric oxide to levels more commonly associated with youth. Among these, exercise stands as the most powerful activator, directly stimulating eNOS and reversing vascular ageing. Sleep acts as the body’s quiet restorer, preserving NO-generating enzymes and protecting against oxidative degradation. Dietary nitrate offers a complementary, oxygen-independent pathway, especially critical when the eNOS system is compromised.
The integration of beetroot juice into cured meats, such as bacon, exemplifies how tradition and science can intersect to create functional foods tailored for modern physiological needs. By rethinking conventional processing practices in light of molecular biology, we unlock new potentials for food as medicine.
In the end, the preservation of nitric oxide is not a trivial biochemical concern—it is the key to sustained human function. Those who learn to maintain it will not only feel younger but will, in many measurable ways, be younger.
References
Green, L. C., Tannenbaum, S. R., and Goldman, P. (1982). Nitrate and nitrite in human saliva, gastric juice, plasma, and urine: dietary sources and endogenous synthesis. Science, 216(4542), 1131–1134.
Hord, N. G., Tang, Y., and 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.
Kapil, V. et al. (2010). Inorganic nitrate supplementation lowers blood pressure in humans: role for nitrite-derived NO. Hypertension, 56(2), 274–281.
Kingwell, B. A. (2000). Nitric oxide-mediated metabolic regulation during exercise: effects of ageing. Exercise and Sport Sciences Reviews, 28(2), 53–58.
Larsen, F. J. et al. (2006). Effects of dietary nitrate on blood pressure in healthy volunteers. The American Journal of Clinical Nutrition, 83(1), 114–117.
Lauer, T. et al. (2001). Nitric oxide and ageing: endothelial dysfunction in humans is associated with eNOS uncoupling. Circulation, 103(22), 2734–2739.
Lundberg, J. O., Weitzberg, E., and Gladwin, M. T. (2008). The nitrate–nitrite–nitric oxide pathway in physiology and therapeutics. Nature Reviews Drug Discovery, 7(2), 156–167.
Lundberg, J. O., and Weitzberg, E. (2010). NO-synthase independent NO generation in mammals. Biochemical and Biophysical Research Communications, 396(1), 39–45.