Nitric oxide supplementation: Science and the scam

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

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

In the equine industry, however, this rush to turn scientific discoveriesinto profit seems to be occurring at an ever-quickening pace. It sometimesseems that as soon as a discovery or new piece of basic science informationis released, there is a supplement, crème or a liquid that containsit, ready to be sold to the horse owner. And, if that new discovery relatesto anything that may improve the performance of the equine athlete, manyowners are all too willing to try it; often before they have educated themselvesabout the product and how it does or does not relate to the discovery thatproduced it.

Equine industry rush

The equine industry is experiencing just such a rush at this time ascompanies 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 NobelPrize in Physiology or Medicine for Robert Furchgott, Louis Ignarro andFerid Murad. These researchers showed that this heretofore little regardedgas molecule represents a new method of cellular communication and thatNO is very important in the regulation of a number of body functions. NOwas originally known to be produced in bacteria but was thought to be unimportantin higher life forms. It is a common gas found in air pollution, producedin automobile exhaust when nitrogen burns. As a molecule it is a potentfree radical and it is highly unstable in the body. What the Nobel Prizeresearchers showed, however, was the unique ability of NO to function asa signal molecule.

Signal molecules are produced in the body all the time. Norepinephrineand acetylcholine are examples of signal molecules that function in thenervous system. These molecules transmit information across the synapsesof nerves and transform nervous energy to chemical energy and back to nervousenergy to produce nerve responses. In this manner, signal substances areproduced within a cell and then released. They are then distributed to anotherarea of the body where they serve to carry, transmit or "signal"information to other cells. NO is unusual in that it is the first exampleof 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 ofthis molecule are far-reaching.

Far-reaching effects

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

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

This early work showing NO's effects on blood pressure regulation leadother researchers to look for a possible link between NO and certain problemsand conditions in the exercising horse where blood pressure changes canbe crucial. Drs. Kindig, Erickson and Poole at the College of VeterinaryMedicine at Kansas State University have been looking at precisely thisarea as it relates to exercise induced pulmonary hemorrhage (EIPH) in theracehorse.

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

There are many theories as to the cause of this increased pressure andthis is where questions about NO's role occur. NO was previously shown toreduce the severity of EIPH and therefore to, possible, favorably affectperformance. It has been suggested that increased pulmonary arterial pressuresthat produce EIPH may be caused by increased arterial flow during exercisewithout a corresponding increase in venous outflow. Alterations in NO concentrationsin the lungs may be at the root of these pressure changes.

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

Other studies have linked NO to healing on a local level following tissuetrauma. Researchers at the University of California-Davis Veterinary TeachingHospital 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 havesome influence. These areas range from nerve conduction to immune systemfunction to cardiac blood flow. It is therefore not surprising that companieshave 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 isdifficult to measure. Specialized equipment is required to look for levelsof nitrate and nitrite left when NO breaks down.

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

Additionally, these supplements are basically composed of the aminoacids L-arginine and L-glutamine along with vitamins C, E and other mineralsand natural proteins. A performance horse eating a good quality diet hasgenerally adequate levels of all these components. Horse owners are cautionedthat no research studies have shown that any of these products actuallyincrease NO synthesis or concentrations.

Pretenders

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

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

Dr. Tom Burke, Ph.D., one of the researchers at Equi-Light, advises cautionwhen looking at seemingly similar products and states, "some of theseproducts 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 importantcomponent in the field of molecular communication and that this moleculemay have tremendous influence on many conditions in the horse.

Additionally, alterations in NO levels may be a valid means of improvingperformance. It is important to understand the fundamental science behindnitric oxide and to be able to educate clients as to the potential benefitsof new products, while counseling them as to the potential problems. Quickleaps 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.