Introduction

Nitric oxide synthase (NOS) is an enzyme responsible for producing nitric oxide (NO), a signaling molecule that plays a crucial role in various physiological processes, including vasodilation, immune response, and neurotransmission. Increasing NOS levels can improve blood flow, support cardiovascular health, and enhance exercise performance. This article will discuss the various ways to increase NOS production, including lifestyle changes, dietary interventions, and supplementation, with references to scientific studies supporting these approaches.

Lifestyle Changes

A. Exercise

Regular physical activity has been shown to increase NOS production by promoting the expression and activity of endothelial nitric oxide synthase (eNOS) (1). Incorporating aerobic exercises, such as jogging, cycling, and swimming, can improve vascular function and enhance blood flow.

B. Sun Exposure

Moderate sun exposure can stimulate eNOS activity, thereby increasing NO production. Ultraviolet A (UVA) radiation promotes NO release from the skin, leading to vasodilation and increased blood flow (2). Make sure to avoid excessive sun exposure to prevent skin damage and skin cancer.

Dietary Interventions

A. Nitrate-rich Foods

Dietary nitrates, found in vegetables such as beetroot, spinach, and arugula, can increase NO production by providing a substrate for eNOS (3). Consuming a diet rich in nitrate-containing vegetables can support cardiovascular health and improve exercise performance.

B. Antioxidant-rich Foods

Foods high in antioxidants, such as berries, dark chocolate, and green tea, can promote eNOS activity by reducing oxidative stress (4). Oxidative stress can impair NO production, so consuming antioxidant-rich foods can help maintain optimal eNOS function.

Supplementation

A. L-arginine

L-arginine is an amino acid that serves as a substrate for NOS, facilitating NO production (5). Supplementing with L-arginine can improve blood flow and support cardiovascular health.

B. L-citrulline

L-citrulline is another amino acid that can increase NO production by increasing L-arginine levels in the body (6). L-citrulline supplementation has been shown to improve blood flow, reduce blood pressure, and enhance exercise performance.

C. Nitrate Supplements

Nitrate supplements, such as beetroot juice, have been shown to increase NO production and improve exercise performance by providing nitrates as substrates for eNOS (7). Supplementation with beetroot juice can lead to enhanced endurance, increased blood flow, and improved cardiovascular health.

D. Quercetin

Quercetin, a natural flavonoid found in foods like onions, apples, and berries, has been shown to increase eNOS expression and activity, thereby enhancing NO production (8). Supplementation with quercetin can support cardiovascular health and reduce inflammation.

E. Pycnogenol

Pycnogenol, a patented extract derived from French maritime pine bark, has been demonstrated to increase eNOS expression and NO production (9). Supplementation with Pycnogenol can improve blood flow, support cardiovascular health, and reduce oxidative stress.

Conclusion

Increasing nitric oxide synthase production in the body can be achieved through a combination of lifestyle changes, dietary interventions, and supplementation. Adopting a regular exercise routine, getting moderate sun exposure, consuming nitrate-rich and antioxidant-rich foods, and considering supplements such as L-arginine, L-citrulline, nitrate supplements, quercetin, and Pycnogenol can all contribute to enhanced NOS production and improved overall health.

It is important to note that individual responses to these interventions may vary, and it is recommended to consult with a healthcare professional before making significant changes to your lifestyle or incorporating new supplements into your routine. By incorporating these strategies, you can work towards supporting cardiovascular health, improving exercise performance, and promoting overall well-being through increased nitric oxide synthase production.

Arginine and Citrulline

L-arginine and L-citrulline are amino acids that play crucial roles in NO production. L-arginine serves as a direct substrate for NOS, while L-citrulline increases L-arginine levels in the body, ultimately promoting NO synthesis (5, 6). Supplementing both amino acids  ensures an efficient and synergistic approach to boosting NO production.

Beetroot

Beetroot is a rich source of dietary nitrates, which provide substrates for eNOS and increase NO production (3). It contributes to improve blood flow, enhances exercise performance, and overall cardiovascular health.

Grape Seed, Grape Skin, and Pomegranate

Grape seed, grape skin, and pomegranate are potent sources of polyphenols and antioxidants, which can support eNOS activity by reducing oxidative stress (4). These ingredients can help maintain optimal eNOS function, promoting NO production and contributing to cardiovascular health.

Vitamin E and Vitamin C

Vitamin E and vitamin C are antioxidants that help protect cells from oxidative damage, which can impair NO production. (10)

Vitamin D and Vitamin K

Vitamin D has been shown to increase eNOS expression, thereby enhancing NO production (11). Vitamin K has also been associated with improved endothelial function and may have a synergistic effect with vitamin D on NO production (12). 

References:

(1) Green, D. J., Maiorana, A., O’Driscoll, G., & Taylor, R. (2004). Effect of exercise training on endothelium‐derived nitric oxide function in humans. The Journal of physiology, 561(1), 1-25. https://doi.org/10.1113/jphysiol.2004.068197

(2) Liu, D., Fernandez, B. O., Hamilton, A., Lang, N. N., Gallagher, J. M., Newby, D. E., … & Feelisch, M. (2014). UVA irradiation of human skin vasodilates arterial vasculature and lowers blood pressure independently of nitric oxide synthase. Journal of Investigative Dermatology, 134(7), 1839-1846. https://doi.org/10.1038/jid.2014.27

(3) 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. https://doi.org/10.3945/ajcn.2008.27131

(4) Förstermann, U., & Li, H. (2011). Therapeutic effect of enhancing endothelial nitric oxide synthase (eNOS) expression and preventing eNOS uncoupling. British journal of pharmacology, 164(2), 213-223. https://doi.org/10.1111/j.1476-5381.2011.01395.x

(5) Böger, R. H. (2004). The pharmacodynamics of L-arginine. Journal of Nutrition, 134(10), 2807S-2811S. https://doi.org/10.1093/jn/134.10.2807S

(6) Bailey, S. J., Blackwell, J. R., Lord, T., Vanhatalo, A., Winyard, P. G., & Jones, A. M. (2015). L-citrulline supplementation improves O2 uptake kinetics and high-intensity exercise performance in humans. Journal of Applied Physiology, 119(4), 385-395. https://doi.org/10.1152/japplphysiol.00192.2014

(7) Jones, A. M., Thompson, C., Wylie, L. J., & Vanhatalo, A. (2018). Dietary nitrate and physical performance. Annual review of nutrition, 38, 303-328. https://doi.org/10.1146/annurev-nutr-082117-051622

(8) Larson, A. J., Symons, J. D., & Jalili, T. (2012). Therapeutic potential of quercetin to decrease blood pressure: a review of efficacy and mechanisms. Advances in Nutrition, 3(1), 39-46. https://doi.org/10.3945/an.111.001271

(9) Enseleit, F., Sudano, I., Périat, D., Winnik, S., Wolfrum, M., Flammer, A. J., … & Lüscher, T. F. (2012). Effects of Pycnogenol on endothelial function in patients with stable coronary artery disease: a double-blind, randomized, placebo-controlled, cross-over study. European Heart Journal, 33(13), 1589-1597. https://doi.org/10.1093/eurheartj/ehr482

(10) Tousoulis, D., Kampoli, A. M., Tentolouris, C., Papageorgiou, N., & Stefanadis, C. (2012). The role of nitric oxide on endothelial function. Current Vascular Pharmacology, 10(1), 4-18. https://doi.org/10.2174/157016112798829760

(11) Andrukhova, O., Slavic, S., Zeitz, U., Riesen, S. C., Heppelmann, M. S., Ambrisko, T. D., … & Erben, R. G. (2014). Vitamin D is a regulator of endothelial nitric oxide synthase and arterial stiffness in mice. Molecular Endocrinology, 28(1), 53-64. https://doi.org/10.1210/me.2013-1252

(12) Vossen, L. M., Schurgers, L. J., van Varik, B. J., Kietselaer, B. L., Vermeer, C., Meeder, J. G., … & de Leeuw, P. W. (2015). Menaquinone-7 supplementation to reduce vascular calcification in patients with coronary artery disease: rationale and study protocol (VitaK-CAC Trial). Nutrients, 7(10), 8905-8915. https://doi.org/10.3390/nu7105423