Better Gut, Brain, and Immunity through Nitric Oxide

The gut-brain-immunity axis is the subject of much dialogue and research as of late. Certainly, we are only scratching the surface of our knowledge about the role our gut, and more critically our gut biome, play in the overall mechanics of our finely-tuned bodily systems. It is also not new news that the health of our gut also has implications for immunity. Many things can contribute to the health or destruction of the gastrointestinal flora – but you may be surprised to learn that addressing some basic principles of healing can have an overall positive impact on the health of our gut, as well as our brain and immune systems, in the capacity that they function independently as well as collectively.

Nitric Oxide, often called the “miracle molecule”, touches every single physiological process. A Nobel Prize was awarded to research on Nitric Oxide in 1998, and much more has been uncovered since about the power of this singular molecule. Nitric Oxide (NO), acts as a signaling molecule in our bodies, cueing vasodilation. Through its role as a vasodilator, NO governs circulation and microcirculation – the adequate function of which is the basis of all healing processes. Thus, optimizing the body’s ability to produce NO over time is critical to essential health and longevity.

Our body uses two pathways to make NO. One is by the oxidation of arginine – which relies on a healthy, coupled NOS enzyme in order to produce NO. The second pathway leverages nitrates – often found in leafy greens and beetroot – for conversion into NO.

I mentioned a “coupled” NOS enzyme required for the oxidation of arginine – this is a critical element that is unfortunately subject to dysfunction or uncoupling. Studies show that the arginine concentration in the serum is rarely too low for the binding capacity for the NOS enzyme. A true arginine amino acid deficiency is rare. Arginine is an amino acid that has multiple pathways that it is able to go down, not just the NOS enzyme.

By the time we are 40, NOS is only functioning around 50% and by the time we are 60, NOS functions only around 15%. When NOS is dysfunctional or uncoupled, it becomes a superoxide generator, not a NO producer. Increasing arginine intake cannot make a dysfunctional, uncoupled NOS function to increase NO. Giving/taking arginine when NOS is uncoupled can increase oxidative stress even more. Arginine is able to be metabolized into ADMA (asymmetric dimethyl arginine) which increases oxidative stress and is associated with all-cause mortality.

Increasing arginine intake increases the enzyme arginase. Arginase increases the metabolization of arginine into ornithine and urea. Urea is considered a waste product. Too much deposition of urea in the kidneys has a devastating effect up to and including kidney failure. Arginine supplementation can also increase ammonia which is highly toxic and can have devastating biological effects if not cleared adequately.

Fortunately, the second Nitric Oxide production pathway – fueled by adequate dietary nitrate, can be primed to produce enough Nitric Oxide to compensate for an uncoupled NOS enzyme, without the dire downstream consequences. Not only does this second pathway increase NO directly, nitrates help repair an uncoupled NOS enzyme – further improving the body’s ability to make its own NO, and reducing superoxide production and oxidative stress – all with impacts on immunity.

Studies show that is takes 300-400mg of nitrate to make the desired physiological changes like a decrease in blood pressure or increase in exercise endurance. That is approximately equal to 5oz of spinach or 7oz of beets. Veggie concentration is variable, though. Veggies grown in different environments under differing conditions have varying amounts of nitrate. In fact, organic veggies, on the whole, have a lesser amount of nitrate than non-organic. Some other high nitrate veggies are arugula, butter lettuce, bok choy and celery. It is estimated that the US population consumes about 150mg of nitrate per day over 2-3 meals. We are a nitrate deficient population. Nitrate supplements, on the other hand, provide a standardized, clinical amount of nitrate in each dose, equal to that of 5oz of spinach of 7oz of beets.

This Gut, Brain and Immunity content is authored by Beth Shirley and was originally posted on

The Secret to Unlocking Better Gut, Brain, and Immunity to be continued….

Beth Shirley, RPh, CCN
Beth Shirley, RPh, CCN, developed an expertise as a pharmacist and certified clinical nutritionist during a 40+ year career. She has been a pioneer at the cutting edge of the evolution of what has now come to be known as integrative pharmacy… the junction between traditional pharmacy and the clinical use of nutritional supplementation.

Since 2009, Beth has spent time working with some of the leading thought leaders in the world of nitric oxide research and through this has developed and in-depth knowledge on the topic and its potential applications in patient care.

She is currently the Executive Director of the Scientific Advisory Board at Berkeley Life.

Want to learn even more? Listen to episodes 75 and 111 of the Biohacking Superhuman Performance podcast, hosted by Nathalie Niddam, on your favorite podcast app!

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