What is Nitric Oxide? Complete Guide Reveals Vital Truths to Help You…
Nitric oxide (also known as nitrogen oxide or nitrogen monoxide) is a gas naturally produced in the body from the breakdown of the amino acid “arginine”.
It has the chemical formula NO.
It is one of the few gaseous signalling molecules that have been identified and its function determined.
It is naturally occurring in the human body and serves as a cell signalling molecule (cell signalling molecules transmit instructions/ information from one cell to another to bring about a desired response).
History of NO 2
In 1998, the Nobel Prize for Medicine was given to three scientists that discovered the signalling role of nitric oxide.
Funny enough, Alfred Nobel, the founder of the Nobel Prize, was prescribed nitroglycerin over 100 years ago by his doctor to help with his heart problems.
He was skeptical, knowing nitroglycerin was used in dynamite, but this chemical helped with his heart condition. Little did he know that nitroglycerin acts by releasing nitric oxide which relaxes narrowed blood vessels, increasing oxygen and blood flow to the heart.
Occurrence In Nature
Nitric oxide occurs naturally from lightning strikes, the combustion of fuel, coal and oil at electric plants and also from the combustion of fuel in vehicles.
It has a very short lifespan as it reacts with the oxygen in air to form nitrogen dioxide; a pollutant. Nitric oxide itself is scientifically referred to as arginine-alpha-keto-glutarate, or AAKG.
Nitric oxide in the body occurs naturally from a breakdown of ‘L-arginine’ , an amino acid which is its precursor compound. After it is formed, it acts as a gaseous signaling molecule.
Functions of Nitric Oxide
The nitric oxide molecule when released by the arterial lining is responsible for ensuring vasodilation (expansion) of the blood vessels in its surrounding vicinity and increasing blood flow.
The functions of nitric oxide are listed in the table below
Vasodilation(expansion of blood vessels)
Regulates cardiac contractions
Relieves the pain of angina
Controls vascular tone
Regulates inflammation and oedema
Promotes wound healing
Has antimicrobial properties
Enhances capacity to store food
Sterilization of swallowed food
Controls the function of sphincters
Promotes better learning functions
Promotes improved memory
Development of erectile functions in male
Synthesis in The Body
It is produced from the precursor amino acid ‘L-arginine’. It may be formed from citrulline malate as well.
Most individuals who use nitric oxide as an exercise supplement take it in the form of its precursor amino acid compound, L-arginine or citrulline.
Citrulline is turned into arginine in the kidneys and results in better and longer lasting elevations of plasma arginine levels than supplementation with L-arginine itself.
It also elevates the plasma content of ornithine; another amino acid which helps reduce exercise-induced fatigue.
Contrary to their names, many nitric oxide supplements do not contain any actual nitric oxide.
In fact, the central ingredient in all nitric oxide supplement products is the amino acid Arginine (or L-arginine), and more recently Citrulline malate, a more efficient source of arginine.
Furthermore, nitric oxide may be derived from inorganic nitrates in vegetables, cured meats, etc.
So, How Does It Work?
Before its discovery as a gaseous signaling molecule, nitric oxide was classified along with several other compounds under the name endothermic-derived relaxing factor (EDRF). EDRF was later discovered to be majorly nitric oxide.
Nitric oxide relaxes vascular smooth muscle by binding to the heme moiety of cytosolic guanylatecyclase, activating guanylatecyclase and increasing intracellular levels of cyclic-guanosine 3′,5′-monophosphate, which then causes expansion of the blood vessel.
The vasodilation in turn increases the flow of blood carrying oxygen and nutrients to other parts of the body.
How Is It Stored In The Body?
It does not usually exist as nitric oxide in the body due to its unstable nature but reacts with other molecules to form more stable products.
- Reaction with oxyhaemoglobin
In the blood, it has a very short half-life and rapidly oxidizes to nitrite. It is then further oxidized with oxyhaemoglobin to produce nitrate.
It also reacts directly with oxyhaemoglobin to give rise to methhaemoglobin and nitrate.
- Reactions with cysteine
Reactions with cysteine residues in proteins lead to formation of nitrosylated products. Because of its high affinity to sulfhydryl groups (thiols), S-nitrosothiols (RSNOs) are the most common nitrosylated product in plasma.
Nitrate is the main storage form of nitric oxide. It is very stable when compared with other storage forms like nitrites and RSNOs, but these are important carriers and donor molecules.
What Causes Loss of NO-2 from the Body?
There are several factors at play in the decrease of nitric oxide in our bodies. These are just a few of them.
As humans advance in age, the ability of the body to produce it may become compromised.
This results in a lower level of NO 2 and potentially dangerous effects. Men and women over the age of 40 experience more than 40% decrease in levels.
- Poor dietary choice:
People who eat too little nitrate-rich foods may find it more difficult to keep up with the body’s demand for nitric oxide.
- Lack of exercise:
Exercise stimulates growth of muscles and increase in strength and performance. A lifestyle that is devoid of exercise is likely to promote a deficiency in NO.
- Overuse of mouthwash
Mouthwash may react with oral nitrates which is a major precursor to the formation of nitric oxide. It kills the good bacteria in the mouth.
The release of the stress hormone improves performance for a short time but afterward begins to clash with its functioning.
Such as antacids are also one of the culprits. They inhibit the function of nitric oxide by changing the pH of the body
Can cause decreases of this important process in our bodies
- Other Factors
Symptoms of Nitric Oxide Deficiency
You might be thinking you are getting older and you do not have energy like you used to. If you are experiencing any of the following symptoms, it may be time to check your Nitric oxide levels:
- Fatigue or low energy levels
- Decreased workout potential
- Less energy at the gym
- Less stamina / endurance
- Decreased libido
- Erectile Dysfunction
- Loss of stamina
- Decreased heart function
Effects of Deficiency
Deficiency in nitric oxide may if left untreated contribute to other chronic diseases such as
- Congenital disorders such as pyloric stenosis, etc.
Causes and Effects of Excess NO
Consuming foods rich in nitrates and nitrites increases the level of nitric oxide and its storage form. Just as deficiency of nitric oxide can lead to disease, too much nitric oxide can also cause disease.
- Effect on central nervous system
It is released into the cerebral vasculature, brain tissue and nerve endings.It may cause headache and migraines. It may damage brain cells leading to neuro-degenerative diseases like Parkinson disease, Alzheimer disease, etc.
- Effect on Pancreas
Nitric oxide produced by β cells in the pancreas may damage the cells (apoptosis) causing diabetes.
- Effect on Skin
In the skin, ultraviolet radiation may lead to excessive nitric oxide production.
Some Major Benefits of Nitric Oxide
Nitric oxide benefits are numerous and applicable to different areas of life. While it may be used by body builders to optimize performance, it could also be used by patients suffering from heart disease and even people suffering erectile dysfunction.
- Increased Glucose Breakdown
Are you interested in weight loss, nitric oxide supplement is a golden resource. Recent research has shown that individuals who use NO supplements pre-workout have increased glucose rates of appearance, glucose rates of disappearance and glucose clearance rate.
The using up of the glucose translates directly to loss of fatty tissues for the individual.
In this manner, it will give you the best results for your workout by basically multiplying your efforts even without an increase in intensity or repetitions of your exercise routine.
- Increased Muscle Strength and Energy
In the process of exercising and weight lifting, stress is placed on the muscular tissues of the body.
In order to compensate for the actions required of the muscles, the heart pumps blood faster to ensure that enough oxygen gets to the tissues.
The release of nitric oxide by the arterial lining causes the walls of the blood vessels to relax and allow more blood pass through.
This extra blood is then able to compensate for the oxygen needs of the muscle and help you continue working out and lifting.
Not even the best energy pills can boast of doing what it does. Nitric oxide is the only supplement that increases energy at the cellular level.
- Increased Endurance and Shorter Recovery Time
Due to the mechanism of action of nitric oxide and its ability to cause vasodilatation, it is able to boost not only muscle strength but also endurance.
As the flow of blood to the muscle is increased, there is an increase in the amount of oxygen available for tissue usage.
This extra oxygenation makes it possible for an individual exercising to increase the protocol i.e. carry out more repetitions.
In this manner, this is also of use to long distance runners as the same pathway ensures that they do not burnout too quickly and serves as an excellent recovery formula when they begin to feel worn out.
- Reduced post-workout fatigue
In the same vein, it speeds up the removal of lactic acid build up which would otherwise occur during and after exercise.
Furthermore, the use of NO supplement causes a decrease in the levels of fatigue experienced by individuals engaged in exercise activities.
As you perform your weight lifting exercises, the body rapidly begins to run out of oxygen. When it does, you’ll start to get lactic acid build-up forming in the muscle tissue, which then leads to quite a high level of fatigue.
Often, this fatigue is felt as a burning sensation and causes you to cease exercise.
So if you can get more oxygen to the tissues, thereby reducing the amount of lactic acid build-up and correspondingly the amount of fatigue, you will dramatically reduce post workout tiredness.
- Reduced risk of heart disease
In addition to all these aforementioned benefits, its role as a vasodilator helps to reduce the risk of heart disease by decreasing plaque and reducing blood clotting.
It relaxes the walls of the blood vessels allowing easier and more efficient blood flow. It is used in the form of nitroglycerin to treat heart conditions.
- Improved Sexual Health
Thanks to the increased circulation, both men and women who use nitric oxide supplements will experience an increase in libido as a positive effect of using this supplement.
- Improved Immunity
It also aids the lysis of bacteria and other germs within the body and the increased blood flow helps to improve immunity and reduce inflammation from stressful activities.
- Great for women
There are several supplements that are restricted in their use to only members of the male gender and are reportedly unsafe for women.
With nitric oxide, it’s a win-win situation for both men and women as there are no gender- based restrictions.
- Improved Vascularity:
Growth of muscles as a consequence of exercise optimized by nitric oxide use leads to a larger network of blood vessels.
This is because the more a muscle is worked out, the more blood, oxygen and nutrients it will need. Therefore, its baseline is adjusted in accordance with the body’s needs.
Who Can Benefit From Taking NO-2 Supplements?
Every human being needs nitric oxide to survive and optimize body functioning. If the stores of nitric oxide are depleted, some pathways and even medication can be compromised.
However, some individuals may benefit from using nitric oxide more than others. Some of these situations are listed below.
Nitric Oxide Supplements For Athletes and Bodybuilders
Increasing nitric oxide has become the new secret weapon for athletes and bodybuilders. Athletes are now taking supplements with L-arginine and L-citrulline to support the flow of blood and oxygen to the skeletal muscle.
They also use them to facilitate the removal of exercise-induced lactic acid build-up which reduces fatigue and recovery time.
Since arginine levels become depleted during exercise, the entire arginine-nitric oxide – citrulline loop can lose efficiency, causing less-than-ideal nitric oxide levels and higher lactate levels.
Supplements can help restore this loop allowing for better workouts and faster recovery from workouts.
Benefits to heart disease and stroke Patients
It has gotten a lot of attention for its cardiovascular benefits. The interior surface (endothelium) of your arteries produces nitric oxide.
When plaque builds up in your arteries, called atherosclerosis, you reduce your capacity to produce NO2, which is why physicians prescribe nitroglycerin for heart and stroke patients.
Benefits of NO2 Supplements to erectile dysfunction Patients
Viagra and other impotence medications work due to their action on the nitric oxide pathway. One cause of impotence is unhealthy and aged arteries that feed insufficient blood to the sexual organs.
Viagra works by influencing enzymes in the nitric oxide pathway, causing a cascade of enzymatic reactions that enhance nitric oxide release, causing increase in blood flow and return of penile erection.
How To Increase Nitric Oxide Levels (Foods, Supplements & Exercises)
It is synthesized in the human body by Nitric Oxide Synthases (NOS). NOS has three isoforms which perform different functions.
Human beings have the ability to produce the nitric oxide they need by several mechanisms:
- From the amino acids L-arginine and L-citrulline via the nitric oxide synthase pathway.
- From inorganic nitrates in food and supplements.
In cases where there is a deficiency, foods and supplements can be used to boost nitric oxide levels.
1) Food as a Means of Boosting Nitric Oxide
Some foods are a source of inorganic nitrates. The pathway by which inorganic nitrates are converted from NO foods is entirely different from the process by which it is synthesized from Arginine. Some foods which are rich in nitric oxide are;
One of the plants with the highest nitrate content is spinach. It is a great source of dietary nitrate which can be converted to nitric in the body
Nuts are a great source of L-arginine, the precursor compound of nitric oxide which boosts its levels significantly.
Examples include pistachios, peanuts, cashew nuts and almonds. In addition to this, most nuts are a source of good fat in the diet. So it’s win-win situation.
Fruits such as watermelon contain huge quantities of the amino acid L-Citrulline which is the more powerful precursor.
The L-citrulline is converted to nitric oxide in the body. Pomegranates and cranberries are other great foods for its production.
Studies have shown that pomegranates can boost testosterone levels by about 22% and can reduce arterial plaque by up to thirty percent. Similar studies have also shown that cranberries can also reduce blood pressure.
- Beets/ Beetroot
Beets are one of the best plants for increasing nitric oxide. This is because they have one of the highest quantity of nitrates of all plants. They are also capable of lowering estrogen levels.
Walnuts are a great source of Arginine, the precursor compound of nitric oxide. Also, they are packed with vitamin E which can boost testosterone and lead to improved sexual health.
Research has shown that garlic is a potent activator of the nitric oxide synthase pathway. It has a similar effect to Viagra and can reduce systolic and diastolic blood pressure by up to eight points.
Several studies have shown that ginseng (Korean type) consumption can improve blood circulation, boost testosterone, increase NO levels, promote sleep and reduce free radicals.
- Raw cocoa
There is scientific evidence to show that raw cocoa can help heal the lining of blood vessels. Also, raw cocoa has been shown to increase nitric O levels while at the same time lowering blood pressure.
Other studies show that dark chocolate contains antioxidants which can help with the elimination of harmful free radicals.
- Citrus Fruits
Nitric oxide is a very reactive molecule with a short half life. Consuming antioxidants along with Nitric oxide precursors can help preserve nitric oxide for use in the body.
Honey contains numerous enzymes that aid the synthesis of nitric oxide. It also contains nitrates which boost NO production.
Peppers contain a high amount of capsaicin. The consumption of pepper capsaicin has been shown to be proportional to the relaxation of arteries and flow of blood.
Kale contains a good quantity of coenzyme Q10 and nitrates. They work together to boost nitric oxide production. Also, kale can boost testosterone levels.
Several other foods that can boost nitric oxide production include salmon, dairy, animal organs, onions, shrimp, meat, etc.
2) Supplements as a Means of Boosting NO
In order to get quicker results than can be produced by diet, supplements may be taken.
NO2 is an excellent muscle recovery supplements as it encourages growth and even improves vascularity of the muscles.
More blood with oxygen and nutrients equals faster muscle growth. The supplements that may be used include but are not limited to;
- L-Arginine and L-Citrulline:
Arginine supplements can be used to boost nitric oxide levels in the body. However, citrulline is even more effective in carrying this action out because it can cause a prolonged increase to its levels. These are usually taken in the form of pills and they have the fewest side effects
- Hawthorn Extract:
Hawthorn extract has been used for cardiovascular diseases for centuries. Recent trials have demonstrated its efficacy for the treatment of heart failure, and the results of several small trials suggest it may lower blood pressure. Hawthorn extract aids its action.
- Grape Seed Extract:
This is an extract derived from grape seed,Studies have shown that grape seed extract has the ability to improve the activity of the nitric oxide synthase pathway by up to 138%.It also improves the arterial flow and helps boost testosterone levels.
Pycnogenol stimulates endothelial synthase to promote the production of nitric oxide in the arteries and cause vasodilation.
Recent studies suggest that exposure to sunlight may help produce nitric oxide. This is in addition to the already established production of vitamin D that sunlight provides.
This compound occurs naturally in onions, garlic, chives, apples and grapes. It works very well in conjunction with other flavonoids and supplements.
- Coenzyme Q10:
This molecule occurs naturally in the mitochondria of cells and helps boost energy levels. The body has the ability to synthesize coenzyme Q10. This ability may be interfered with by compounds such as statins.
In conditions such as this, supplementation may be required. However, there are foods rich in coenzyme Q10 such as grassfedbeef,salmon, egg yolks, spinach, brazil nuts.
Niacin promotes the formation of nitric synthase which increases baseline levels of NO. It also promotes good cholesterol.
This flavonoid has the ability to stimulate nitric oxide synthase enzyme and stimulate production of nitric oxide.
The active compound in the horny goat weed plant (icariin) is great for nitric oxide production, and it also acts as a mild PDE-5 enzyme inhibitor.
How Safe Are Nitric Oxide Supplements?
Although prescription drug manufacturers are closely regulated by the FDA, supplement makers find it easier to get their products on the market.
Nitric oxide is sold by many different manufacturers, so it is not possible to say how safe this supplement is.
Some supplements are better than others while other brands are made in labs that are more hygienic than others. It is imperative that you seek out only the most reputable manufacturers before taking any type of supplement.
The cost of a supplement often has little to do with the process and facilities that were used to produce it. You should speak to a dietician that has experience with health supplements if you want to find the best brand.
3) Exercise to Boost NO-2
The more exercise the body partakes in, the stronger and bigger the muscles grow. Increase in the size of the muscles causes a proportional increase in nitric oxide levels.
This is because the muscles require more energy, blood and nutrients and this raises the No synthase requirements.
This is one of the reasons why weightlifters and body builders have more obvious vasculature.
Can Women Take It?
Nitric oxide supplements can be taken by men and women without requiring any changes in dosage amounts.
Some health supplements should not be used by women. This is because of their ability to interfere with hormones and normal functioning of the body.
However, it is safe for women to use – apart from improving cardiovascular health also plays a role in the relaxation of smooth muscle in the genital area. This helps to increase excitement and prolong arousal.
A study in the University of Pennsylvania in 2003 helped to narrow down one potential enzyme that leads to female sexual dysfunction by inhibiting nitric oxide production.
Women are able to take nitric oxide for years at a time with no breaks and still remain healthy. Although women can generally take it with no problems, anyone that has experienced negative side effects will need to stop taking it.
Nitric oxide will not produce the same exact results in women as it does in men. This is not because this supplement is metabolized any differently in either gender, but because men are biologically designed to develop and maintain more muscle.
Generally, men benefit more greatly from the use of most supplements because their bodies are not inclined to carry much body fat when compared to women.
Men are also able to lose weight more easily through relatively small changes in their exercise and eating habits. Men will also experience faster fat loss with nitric oxide than women.
Some drugs are able to interact with other drugs and cause unpleasant side effects. Medications that should not be used along with nitric oxide include;
- Drugs for Heart Conditions:
Individuals who have heart conditions should consult their physicians before taking any nitric oxide supplements as the supplements may interact with their medication. Some heart medications work by the same mechanism as nitric oxide.
- Drugs for Penile Erection:
Also, it should not be taken with any medication that stimulates penile erection such as Viagra.
- Drugs for Blood Thinning:
Such as warfarin should not be taken along with nitric oxide supplements as this can aggravate bleeding.
Furthermore, other drugs such as ability, fentanyl, Benadryl, Valium, etc may be affected by the presence of NO2.
Most medications which have desirable effects may have undesirable side effects. If used at the correct dosages will cause minimal side effects. These side effects may include;
- Blood Pressure Changes
Because it affects blood vessels, a decrease in blood pressure is a potential side effect. Symptoms associated with low blood pressure include headache, dizziness, lightheadedness, nausea, vomiting and loss of balance.
These symptoms may be worse when you are standing from a sitting position or when urinating. Discontinue use and consult your doctor if you are experiencing these symptoms.
- Stomach Discomfort
Stomach discomfort may be a side effect of supplementations. Symptoms include nausea, stomach cramps or an increase in the number of stools.
It is best you take this supplement with food to avoid stomach discomfort. Consult your doctor immediately if you are experiencing stomach discomfort.
- Changes in Body Electrolytes
Supplements may change the chemical environment of your body. This can result in high potassium, high chloride, low sodium, low phosphate, high blood urea nitrogen and high creatinine levels.
You should not use nitric oxide supplements if you have kidney or liver disease. These organs regulate electrolytes and may be sensitive to side effects of nitric oxide supplement use.
- Increased Bleeding
Supplements may increase the risk of bleeding. Therefore, you should ask your doctor about using supplements if you have a bleeding disorder or you are on blood-thinning medications such as warfarin.
- Arginine Injection
Your doctor may give you an arginine injection to increase nitric oxide levels in your body.
Common side effects of arginine injection include low back pain, flushing, headache, numbness, restless legs, irritation of the veins and death of the tissues surrounding the injection site.
You may place an ice pack on the injection site as needed for pain. Experts advice you consult your doctor if these symptoms do not resolve.
Controversy and Opposing Views
Nitric oxide supplements are widely used for bodybuilding and athletic performance, but do they really work? They may not build up your muscles which is their main claim.
But ‘nitric oxide’ supplements may help you exercise intensely a little longer,” says ConsumerLab.com President, Tod Cooperman, M.D.
Supplements don’t actually provide nitric oxide, which is a gas, but generally contain L-arginine that increases nitric oxide.
Nitric oxide, in turn,It potentially increases blood flow to muscles and other organs. In fact, a 2012 review of multiple nitric oxide studies found no conclusive evidence that it did much of anything to help muscle growth.
Some scientists and individuals are of the school of thought that nitric oxide has gained false popularity and claim that studies done in an exercise and endurance situation have failed to prove its effectiveness as a supplement.
The review concluded that while nitric oxide may provide marginal benefits for new athletes (or guys that have just started working out), there were no detectable benefits for more experienced athletes.
Sure, if you want a boost to your muscular endurance – allowing you to work out longer, or for some other sort of endurance-based sport – nitric oxide may be more applicable for you.
And probably you don’t want your gym sessions to be so long that you need a supplement to counteract lactic acid build up.
The only benefits that you’re likely to get by taking a nitric oxide supplement are temporary ones: increased pump and greater endurance at the gym.