By Medifit Biologicals



nitric oxide 01



A compound that is toxic but which, paradoxically, plays a number of important roles in the body, including the following:

  • It acts as a vasodilator (blood vessel relaxant).
  • It therefore controls blood flow to tissues.
  • It regulates the binding and release of oxygen to hemoglobin.
  • It thereby controls the supply of oxygen to mitochondria (cell powerhouses that generate energy).
  • It kills parasitic organisms, virus-infected cells, and tumor cells (by inactivating respiratory chain enzymes in their mitochondria).
  • It stimulates the production of new mitochondria.

The 1998 Nobel Prize in Medicine or Physiology was awarded to Robert F. Furchgott, Ferid Murad, and Louis J. Ignarro for their discoveries of the role of nitric oxide in cardiovascular physiology.

Basically, nitric oxide is a gas that is produced naturally in the body.

This happens when your body breaks down arginine, which is an amino acid found in many foods – such as spinach, crab, shrimp, and turkey, among many others.

So, if you’re like most guys, you’re getting a good amount of arginine in your diet as it as, meaning that you’re already naturally producing nitric oxide even without taking a supplement.


Moving on, now that we’ve defined what nitric oxide is, let’s briefly go over what it actually does.

In short, nitric oxide plays a role in helping to facilitate transport between different cells in your body.

This includes assisting in blood circulation, and regulating the activities of various bodily organs – such as the lungs, brain, liver, and stomach, just to name a few.

In terms of improving your performance at the gym, though, nitric oxide is primarily taken to help increase blood flow to the muscles.

You see, NO is what’s known as a vasodilator.

This means that it will dilate your blood vessels, making them larger in size and resulting in increased blood flow.


Nitric oxide was first identified as a gas by Joseph Priestly in 1772 and is a simple molecule consisting of just one atom of oxygen and one atom of nitrogen. For much of the time since this discovery nitric oxide, or NO, has been thought of simply as an atmospheric pollutant.

In the 1980’s researchers were investigating how blood vessels dilate (or relax). Dilation of blood vessels, also known as vasodilation, is extremely important for controlling blood pressure as dilated blood vessels have a larger diameter which allows blood to flow with lower pressure. Conversely, constriction of blood vessels narrows their diameter and increases blood pressure.

At the time drugs such as nitroglycerin were given to patients for heart conditions like angina in order to promote vasodilation and reduce blood pressure, but no-one knew how these drugs worked.

In 1980 Robert Furchgott investigated the role of a drug called acetylcholine on vasodilation and found that relaxation of blood vessels only occurred if a special class of cells called endothelial cells were present. Endothelial cells are the cells that line the insides of blood vessels and are in direct contact with the blood (see animation below). Behind the endothelial cells are another specialised type of cell known as smooth muscle cells. The contraction and relaxation of these muscle cells is thought to be responsible for constricting or dilating the blood vessels..

Robert Furchgott and his group found that without the endothelial cells the smooth muscle cells were not able to cause vasodilation. This suggested that there was some kind of factor produced by the endothelial cells that was required for relaxation of the blood vessels. This factor was termed Endothelial Derived Relaxing Factor or EDRF and the search to find and identify EDRF began.


Independently, in 1977 Ferid Murad was investigating how nitroglycerin works and discovered that it can release nitric oxide which in turn was able to cause relaxation of smooth muscle cells.


The pieces of the puzzle were finally put together in 1986 when Louis Ignarro identified EDRF and found that it had identical properties to the gas nitric oxide. This was the first time that a gas had been shown to play an important role in regulating biological functions in humans. For their role in this discovery Furchgott, Murad and Ignarro were awarded the Nobel Prize for Medicine or Physiology in 1998.


Since the discovery of this role for nitric oxide it has been shown to be involved in a large number of other roles, some of which are described here. It has also been shown to be important in s wide variety of different species from plants, to insects and mammals. Only a small number of other gases have been shown to play a role in mammalian cells. These are carbon monoxide and hydrogen sulphide, although these two gases appear to have far fewer role than nitric oxide.



Some people think it’s the gas that makes us laugh at the dentist office. Some think it’s the fuel racecar drivers use to speed up their cars. But it’s neither. Nitric oxide is a molecule that our body produces to help its 50 trillion cells communicate with each other by transmitting signals throughout the entire body.

Nitric oxide has been shown to be important in the following cellular activities:


• Help memory and behavior by transmitting information between nerve cells in the brain

• Assist the immune system at fighting off bacteria and defending against tumors

• Regulate blood pressure by dilating arteries

• Reduce inflammation

• Improve sleep quality

• Increase your recognition of sense (i.e. smell)

• Increase endurance and strength

• Assist in gastric motility

There have been over 60,000 studies done on nitric oxide in the last 20 years and in 1998, The Nobel Prize for Medicine was given to three scientists that discovered the signaling role of nitric oxide.



Nitric oxide has gotten the most attention due to its cardiovascular benefits. 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 nitroglycerin acts by releasing nitric oxide which relaxes narrowed blood vessels, increasing oxygen and blood flow.

The interior surface (endothelium) of your arteries produce nitric oxide. When plaque builds up in your arteries, called atherosclerosis, you reduce your capacity to produce nitric oxide, which is why physicians prescribe nitroglycerin for heart and stroke 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 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, causing more blood flow and better erections.



The most common way to increase nitric oxide is through exercise. When you run or lift weights, your muscles need more oxygen which is supplied by the blood. As the heart pumps with more pressure to supply the muscles with blood, the lining in your arteries releases nitric oxide into the blood, which relaxes and widens the vessel wall, allowing for more blood to pass though. As we age, our blood vessels and nitric oxide system become less efficient due to free radical damage, inactivity, and poor diet, causing our veins and arteries to deteriorate. Think of a fire hose as water rushes through it to put out a fire – it needs to expand enough to handle the pressure, still keeping enough force to put out the fire. Athletes and youth have the most optimal nitric oxide systems, reflecting their energy and resilience.

Another way to increase nitric oxide is through diet, most notably by consuming the amino acids L-arginine and L-citrulline. Arginine, which can be found in nuts, fruits, meats and dairy, and directly creates nitric oxide and citrulline inside the cell (diagram 1).(6) Citrulline is then recycled back into arginine, making even more nitric oxide. Enzymes that convert arginine to citrulline, and citrulline to arginine need to function optimally for efficient nitric oxide production. We can protect those enzymes and nitric oxide by consuming healthy foods and antioxidants, like fruit, garlic, soy, vitamins C and E, Co-Q10, and alpha lipoic acid, allowing you to produce more nitric oxide. Nitric oxide only lasts a few seconds in the body, so the more antioxidant protection we provide, the more stable it will be and the longer it will last. Doctors are utilizing this science by coating stents (mesh tubes that prop open arteries after surgery) with drugs that produce nitric oxide.


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.

With nitric oxide deficiencies due to aging, inactivity, smoking, high cholesterol, fatty diets, and lack of healthy foods, increasing your nitric oxide levels can help increase your energy, vitality and overall wellness. The basic adage of eating well and staying active all makes sense now.


One of the main physiological causes of impotence, or erectile dysfunction, is inability of the blood vessels in the penis to dilate enough to allow blood flow and engorgement. The most important chemical involved in this process is nitric oxide. Arginine, an amino acid available as a supplement, can help make more nitric oxide but the doses required are high and the effects may not last for long. L-Citrulline is a naturally occurring non-essential amino acid, an intermediate in urea cycle and conditionally essential in intestinal pathology. It is a potent hydroxyl radical scavenger and effective precursor of arginine and nitric oxide (NO).


Fortunately, there are several herbal supplements that can help dilate blood vessels, including ginseng and others less known but more powerful. Passion Rx has a combination of several potent herbal extracts that help dilate blood vessels and improve erectile function, along with libido and sensation. Some of the herbs in this libido formula can act to enhance nitric oxide production.


Nitric oxide products, also known as pre-workout, NO, or NO2 products, contain L-arginine, an amino acid that increase the amount of nitric oxide produced in the body. Nitric oxide is a free-form gas that acts to control blood flow in the body. Creatine is an amino-acid-like substance synthesized in the liver from the amino acids glycine, methionine, and arginine. Nitric oxide and creatine may have synergistic health and fitness benefits, but they may also cause side effects in some individuals.



Nitric oxide supplements may aggravate the herpes virus. L-arginine, the main ingredient in NO products, can drastically impact the replication of the herpes virus, causing outbreaks or worsening existing conditions. The amino acid L-lysine helps inhibit the replication of the herpes virus. A diet consisting of low lysine-to-arginine ratios may be responsible for more frequent herpes outbreaks. Anecdotal reports suggest that it is not uncommon to experience a herpes outbreak within days of beginning nitric oxide supplementation. Those with genital herpes or frequent cold sores should avoid NO2 products, decrease arginine consumption and consider supplementing with lysine. Foods naturally high in arginine include chocolate, meat, seafood, and nuts and seeds.



Nitric oxide products create an effect in the body known as vasodilation, which allows blood vessels to relax and opens up pathways for blood flow. This side effect has many benefits for athletic performance, anti-aging and heart health. However, adverse side effects from vasodilation can include the risk of excessive bleeding and low blood pressure. If you’re on heart medications, like blood pressure medication, check with your physician before using any of these products. Nitric oxide supplements mimic this effect and may cause other adverse effects on the heart when combined with certain drugs.


Overdosing with nitric oxide products can be toxic. Adverse effects on waste-handling organs, such as the liver and kidneys, are possible. Too much L-arginine can cause diarrhea, weakness nausea, headaches, increased heart rate and palpitations, water retention, fatigue, skin irritations and dry mouth. Fainting is a common anecdotal side effect reported by users. Serious side effects may include breathing problems, severe allergy or rash, hives, itching, wheezing or life-threatening asthma complications. The Mayo Clinic reports a rare side effect known as anaphylaxis, or shock involving sudden chills, sweating, tremors, vomiting and fainting. Recent heart attack patients, those on blood thinners, pregnant or nursing mothers, and/or those with liver disease or sickle cell anemia should avoid NO2 products completely.


Hypertension is a major risk factor for cardiovascular disease, and reduction of elevated blood pressure significantly reduces the risk of cardiovascular events. Endothelial dysfunction, which is characterized by impairment of nitric oxide (NO) bioavailability, is an important risk factor for both hypertension and cardiovascular disease and may represent a major link between the conditions. Evidence suggests that NO plays a major role in regulating blood pressure and that impaired NO bioactivity is an important component of hypertension. Mice with disruption of the gene for endothelial NO synthase have elevated blood pressure levels compared with control animals, suggesting a genetic component to the link between impaired NO bioactivity and hypertension. Clinical studies have shown that patients with hypertension have a blunted arterial vasodilatory response to infusion of endothelium-dependent vasodilators and that inhibition of NO raises blood pressure. Impaired NO bioactivity is also implicated in arterial stiffness, a major mechanism of systolic hypertension. Clarification of the mechanisms of impaired NO bioactivity in hypertension could have important implications for the treatment of hypertension.


WARNING: If you have an existing heart condition or abnormal blood pressure, please consult your healthcare professional before taking supplements to increase nitric oxide levels.

By Medifit Biologicals