Nitric oxide supplementation: Science and the scam

Nitric oxide supplementation: Science and the scam

Mar 01, 2001

Technological advances made during the space program routinely yielded products and services in the private sector.

The astronauts orbited the moon and pretty soon we had Tang to drink and space age fibers in the clothes that we wore. This process of turning research developments into useful products and services has been going on for a long time.

In the equine industry, however, this rush to turn scientific discoveries into profit seems to be occurring at an ever-quickening pace. It sometimes seems that as soon as a discovery or new piece of basic science information is released, there is a supplement, crème or a liquid that contains it, ready to be sold to the horse owner. And, if that new discovery relates to anything that may improve the performance of the equine athlete, many owners are all too willing to try it; often before they have educated themselves about the product and how it does or does not relate to the discovery that produced it.

Equine industry rush

The equine industry is experiencing just such a rush at this time as companies are now producing supplements aimed at increasing the nitric oxide (NO) level in horses.

This interest in NO is coming out of research that won the 1998 Nobel Prize in Physiology or Medicine for Robert Furchgott, Louis Ignarro and Ferid Murad. These researchers showed that this heretofore little regarded gas molecule represents a new method of cellular communication and that NO is very important in the regulation of a number of body functions. NO was originally known to be produced in bacteria but was thought to be unimportant in higher life forms. It is a common gas found in air pollution, produced in automobile exhaust when nitrogen burns. As a molecule it is a potent free radical and it is highly unstable in the body. What the Nobel Prize researchers showed, however, was the unique ability of NO to function as a signal molecule.

Signal molecules are produced in the body all the time. Norepinephrine and acetylcholine are examples of signal molecules that function in the nervous system. These molecules transmit information across the synapses of nerves and transform nervous energy to chemical energy and back to nervous energy to produce nerve responses. In this manner, signal substances are produced within a cell and then released. They are then distributed to another area of the body where they serve to carry, transmit or "signal" information to other cells. NO is unusual in that it is the first example of a gas signal molecule and represented a new means of cellular communication. It is now known that all living creatures produce NO and the effects of this molecule are far-reaching.

Far-reaching effects

NO has been shown to regulate blood pressure and blood flow through various organ systems.

It is produced in largest quantity in the red blood cells (RBC) and in the cells of the endothelium. The amino acid L-arginine is transported into the RBC and endothelial cells. A specific enzyme, NO synthetase, produces NO in this location. After production, NO is stable for less than 10 seconds so it rapidly diffuses through the endothelium into the muscle cells of the blood vessel. As NO dissolves, it facilitates the phosphorylation of proteins, which cause the relaxation of smooth muscle. NO therefore causes a dilation of the vessel and a decrease in blood pressure.

This early work showing NO's effects on blood pressure regulation lead other researchers to look for a possible link between NO and certain problems and conditions in the exercising horse where blood pressure changes can be crucial. Drs. Kindig, Erickson and Poole at the College of Veterinary Medicine at Kansas State University have been looking at precisely this area as it relates to exercise induced pulmonary hemorrhage (EIPH) in the racehorse.

Clinically EIPH is characterized by increase blood pressure in the arteries of the lungs and with subsequent rupture of the small capillaries in the horse's airways.

There are many theories as to the cause of this increased pressure and this is where questions about NO's role occur. NO was previously shown to reduce the severity of EIPH and therefore to, possible, favorably affect performance. It has been suggested that increased pulmonary arterial pressures that produce EIPH may be caused by increased arterial flow during exercise without a corresponding increase in venous outflow. Alterations in NO concentrations in the lungs may be at the root of these pressure changes.

To evaluate this concept researchers at Kansas State University recently studied five horses exercising on a treadmill at speeds equivalent to those of maximal performance. These horses were tested with and without drugs that blocked the production of NO. In all five horses a reduction in the production of NO during exercise caused an increase in EIPH. Dr. Howard Erickson presented some of the group's research at the last AAEP convention and concluded that, though more research clearly needs to be done, current work "suggests an important role for NO in exercising horses."

Other studies have linked NO to healing on a local level following tissue trauma. Researchers at the University of California-Davis Veterinary Teaching Hospital are seeking to define the role of NO in the equine joint environment. There are preliminary reports of many areas where NO has been shown to have some influence. These areas range from nerve conduction to immune system function to cardiac blood flow. It is therefore not surprising that companies have begun offering supplements that claim to improve the synthesis of, and the eventual levels of, NO in the horse.

Problems with science

There are a few problems with the "science" behind these products, however.

Because NO is unstable and does not stay in the body for long, it is difficult to measure. Specialized equipment is required to look for levels of nitrate and nitrite left when NO breaks down.

The Equi-light Company, producers of photon energy equipment shown to increase the levels of NO in treated areas, has done quality research looking at NO levels in normal horses. Their work showed tremendous variation with levels ranging from almost zero to 300 micromoles. Researchers at Louisiana State University have also reported variations in NO in otherwise normal horses. There is presently no known explanation for the variability but the problem then becomes that, unless you know the pre-supplement level of NO, you would have no way to know if your additives produced any effect on NO. Testing is not standardized and all types of variations can exist when trying to fairly evaluate these products.

Additionally, these supplements are basically composed of the amino acids L-arginine and L-glutamine along with vitamins C, E and other minerals and natural proteins. A performance horse eating a good quality diet has generally adequate levels of all these components. Horse owners are cautioned that no research studies have shown that any of these products actually increase NO synthesis or concentrations.


Topically applied nitroglycerine crème has been shown to produce a large but transient increase in NO in the treated area. This crème is being used to try to increase blood flow in conditions such as acute laminitis and is generally effective locally.

Photon therapy of specific wavelength and intensity has also been associated with local increases in NO levels. There are many such photon energy products on the market and their specifics vary greatly. It is important for veterinarians to understand their variability as these additional links between NO production and possible clinical improvement in certain cases have only made more owners willing to try products claiming to increase NO production.

Dr. Tom Burke, Ph.D., one of the researchers at Equi-Light, advises caution when looking at seemingly similar products and states, "some of these products may work well, but they cannot say so until they do the science."

New and important

There is no question that the NO molecule represents a new and important component in the field of molecular communication and that this molecule may have tremendous influence on many conditions in the horse.

Additionally, alterations in NO levels may be a valid means of improving performance. It is important to understand the fundamental science behind nitric oxide and to be able to educate clients as to the potential benefits of new products, while counseling them as to the potential problems. Quick leaps from basic science to radical new products are rarely justified and, even though most researchers feel that NO studies will yield valuable therapies, only time will tell.