NO, the signal to better life

NO, the signal to better life

February 28, 2024

Very few people, if any, would want to receive a big fat NO. But not if the NO is something that is sure to positively impact on life and health. I refer to NO, the formula for nitric oxide, perhaps the most important signaling molecule produced by the cells for wide use in the body.

What are signaling molecules? These are molecules that are responsible for transmitting information between cells in your body. The size, shape and function of different types of signaling molecules can vary greatly. Some carry signals over short distances, while others transmit information over very long distances. A signaling molecule is also known as a ligand, a chemical messenger released by one cell to signal itself or a different cell. The binding results in a cellular effect, which manifests as any number of changes in that cell. 

Molecules that are referred to as signaling molecules include proteins, peptides, amino acids, nucleotides, steroids, retinoids, fatty acids derivatives, and even dissolved gases such as nitric oxide and carbon monoxide. Hormones are also signaling molecules because of the notable functions of these secretions in terms of metabolism, development, growth and reproduction.

Why is NO called the most important signaling molecule?  Because it acts inside and outside the cell as messenger, NO mediates diverse signaling pathways in target cells and is known to play an important role in many physiological or body processes including neuronal (brain) signaling; immune response (capacity to ward off infection or protect against autoimmune illnesses, such as lupus, etc,); inflammatory response (inflammation, even when silent, is the root cause of many if not all diseases); modulation of ion channels (ions required in production of electrical impulses that enables muscles to contract, including heart muscles); phagocytic defense mechanisms (capacity to immobilize and digest harmful bacteria, fungi, and viruses); sexual arousal in both males and females, and cardiovascular homeostasis or balance.

NO has broad effect across all the branches of medicine-cardiovascular, immunology, neurology, gastroenterology, endocrinology, pulmonary, musculoskeletal, etc.  It is surprising  that this versatile and amazing molecule is underemphasized and under-utilized by many clinicians. NO is not taught even in medical schools.

Of the myriad effects of NO, it is in cardiovascular medicine that it has made the most impact. It works by dilating or relaxing the walls of the blood vessels thereby increasing blood flow, reducing blood pressure. decreasing oxidative stress and inflammation, reducing vascular and cardiac smooth muscle growth, inhibiting platelet aggregation, and preventing leukocyte adhesion to the vessel endothelium (thin and fragile inner lining). It is these last two effects (platelet aggregation and leukocyte adhesion) that have direct bearing in the  induction of heart attacks.

Deficiencies in the bioavailability of NO are related to hypertension, atherosclerosis or hardening of arteries, coronary heart disease, blood vessel effects of diabetes mellitus, dyslipidemia or imbalances in blood stream fats, and stroke (brain strokes, resulting in death or paralysis). By ensuring the continuing production of NO, the three finite responses to cardiovascular disease: inflammation, oxidative stress and vascular immune dysfunction are mitigated.

Because NO is a gas that is short lived, there is no direct test that measures its blood level unlike many other substances. However, there are blood tests that correlate well with its bioavailability and noninvasive vascular tests that determine blood vessel elasticity and compliance. These are sufficient information to enable the clinician to gain a good understanding of the cardiovascular system.

If an ordinary person wants to stay healthy and needs to be assured of steady availability of NO, what must one do? First, it is important to understand that majority of NO is produced naturally in the innermost layer of the human blood vessel, the endothelium, through the action of an enzyme called, eNOS (endothelial nitric oxide synthase). Other counterpart NOS are produced for the brain (nNOS)  and the (immune system (iNOS). Production of NO via the eNOS is age-dependent—it peaks at about at age 20-30 and decreases by about 10 percent for every decade thereafter. By age 60, the NO production is down to about 50-60 percent. 

While not much can be done to bolster the eNOS production of NO, there is another pathway that is dependent on what we eat and the interaction with the naturally occurring bacteria in the mouth. This is the pathway that all of us can benefit from. This is called the Oral Nitrate-Nitrite- Nitric Oxide pathway. 

To understand fully and therefore be able to leverage its daily application, the oral nitrate-nitrite pathway depends on the daily intake of green leafy vegetables and certain fruits that interact with saliva in the mouth. Vegetables and fruits contain dietary nitrates which are the building blocks of nitrite that ultimately are broken down to nitric oxide in the stomach.  Humans do not have the natural enzymes that can break down the nitrates but the commensal bacteria in the mouth can. These classes of bacteria are generally harmless and live symbiotically with the human host.

The production of NO through this pathway takes into consideration the following steps- green leafy vegetables and/or fruits like beets, pomegranates, noni fruits, etc are chewed in the mouth and as admixing is achieved, the salivary bacteria produce enzymes that split the nitrate molecules to nitrites. When swallowed, the partially-digested vegetables and the nitrites are acted upon by the acid in the stomach. The acid reaction catalyzes the conversion of nitrites to nitric oxide, the active gas that is rapidly absorbed into the bloodstream. NO acts on the lining of the vessels, penetrating its walls to relax the underlying muscles of the blood vessels. The relaxation of the blood vessels results in modulation of the blood pressure and produces other benefits to the vessel lining such as ‘cooling’ inflammation.

It is also as important to heed the following reminders: 1. Regular use of antiseptic mouthwash degrades the capacity to produce NO because the antiseptic kills the majority of commensal bacteria that are responsible for the breakdown of nitrates to nitrites.  2. Long- term use of proton pump inhibitors such as pantoprazole or omeprazole for some GI problems removes the production of stomach acid, thereby preventing the conversion of nitrites to nitric oxide.  3. Use of supplements in liquid drops, lozenges or capsules that provide the precursors or building blocks for NO production help ensure a steady supply of the active gas.

Treat our body as a vast and complex eco-system that requires balanced interaction of the various natural stakeholders to achieve synergy.  After all, life is about maintaining balance, in the same way that nature thrives by maintaining balance with the environment.

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