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How Much Do You NO?

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Rob Egbers

Kestrson S., M.D.


UM Medical School





One of the hottest athletic supplements available is L-arginine, marketed as Nitric Oxide.  You can buy it as a pure supplement or as an additive in common mixtures such as BSN NO-Xplode, Xyience NOX-CG3, or any protein supplement.  This article will be a beneficial read for anyone taking or considering an arginine supplement.  Even if you aren't thinking about taking L-arginine, look at the supplements that you are currently taking and there is a good chance you will find it as an ingredient. 

The Basics
L-arginine is an amino acid that is found in high concentrations in nuts, seeds and raisins.  It is used by the body for protein syntheses, wound healing and removing urea and nitrogen waste from the body.  More recently, scientists discovered that L-arginine is the precursor for the gas nitric oxide (NO) produced in the body via the following reaction:



Nitric Oxide Synthase (enzyme)







(Nitric Oxide)

This reaction occurs in neurons, in the immune system where NO acts as a defense mechanism, and in cells which line the blood vessels of your body (endothelial cells).  As athletes, our primary concern is with NO’s ability to dilate our arteries allowing more blood to flow to our muscles, which is called vasodilation.  Under normal conditions, NO is released in blood vessels in response to an increased volume of blood trying to get through the vessels.  These NO molecules then diffuse from the lining of blood vessels to the surrounding smooth muscle cells and allows them to relax.  The idea with supplementation is that by taking more L-arginine your body will be able to produce more NO.  This relaxation allows more blood filled with protein, oxygen and nutrients to flow through the arteries to your muscles, aiding in workout and recovery.

What scientific data do we have to support these claims?
The human body is extremely complex and just because we can theorize how a supplement may help us it doesn’t prove that you will be able to lift more weight or gain more muscle mass.  Experiments with actual people need to be evaluated to determine the effectiveness of supplementation with L-arginine.

So far, studies have shown contradictory evidence on the effects of L-arginine supplementation.  L-arginine supplementation has been shown to increase blood flow in healthy individuals at rest [2,3] and in individuals with certain diseases such as heart failure [1], diabetes, smokers, high cholesterol and high blood pressure [13].  However, research finds no increase in blood flow with arginine supplementation in healthy individuals during exercise [2,3,4], even through NO production has been shown to increase during exercise [5,6].   It has been postulated that this is due to the multitude of other vasodilatory factors at work during exercise such as potassium, hydrogen ions, adenine and prostaglandins [4].  Also, and maybe more importantly, during exercise the production of NO may not limited by the substrate arginine [14].  This means that taking more L-arginine under exercise conditions wont increase the output of NO.

On the other hand, L-arginine supplementation has been shown to have beneficial effects beyond those related to vasodilation.  Some recent publications suggest L-arginine supplementation reduces plasma lactate, ammonia [7,9,10] and blood glucose [8,9,10].  Build-up of lactate and ammonia lead to fatigue during exercise.  Increasing glucose clearance means more energy will be available inside muscle cells to finish a work out.  It has been proposed that the increase in glucose clearance results from an increase in glucose uptake by muscle cells by glucose transporters rather than from vasodilation [8].

A current misconception associated with L-arginine is that it causes an increase in growth hormone release.  Intravenously administered large quantities of arginine has been shown to increase growth hormone secretion (via inhibition of somatostatin).  Orally administered arginine on the other hand has been shown not to increase growth hormone secretion in well trained athletes [11,12].  Part of the problem with orally administered arginine is palatability.  Oral doses that do cause a slight increase in growth hormone in secretion in athletes cause diarrhea and stomach cramping.  Growth hormone has anabolic effects to increase amino acid uptake, protein synthesis, fat mobilization and maintenance of blood glucose concentration.

How safe is this product?
Systems in the human body do not operate in a vacuum.  What you put in to your body could affect more than just the one or two types of cells where the effect is desired.  People with herpes simplex virus should be aware that arginine can stimulate virus growth.  Also a theoretical interaction exists with erectile dysfunction medications or nitroglycerine.  Headache, nausea, diarrhea and weakness have been reported if taken in excess.  Like with any other supplement you want to start, consult your doctor before taking.

Is it worthwhile to take an L-arginine supplement?
It still isn't clear weather or not L-arginine supplementation will give you the increased blood flow you want to improve athletic performance.  More research needs to be done on the subject.  However, research has shown some other benefits of L-arginine supplementation.  Based on the current available information, you should really think twice before shelling out large sums of money on this product.
If you decide to take this product you should know that peak levels of orally administered arginine occur between 1-2 hours after ingestion.  And authors suggested 4-5g of orally administered arginine to decrease plasma lactate and ammonia during exercise [7].

  1. Kanaya, Y., Nakamura, M., Kobayashi, N., Hiramori, K.  Effects of lower limb vasodilator reserve and exercise capacity in patients with chronic heart failure.  Heart 1999; 81:512-517.
  2. Hickner, R.C., Fisher J.S., Ehsani A.A., Kohrt W.M.  Role of nitric oxide in skeletal muscle blood flow at rest and during dynamic exercise in humans.  Am. J. Physio. 1997; 273:405-410.
  3. Wilson, J.R., Kapoor, S.  Contribution of endothelium –derived relaxing factor to exercise-induced vasodilation in humans.  Am. J. Physio. 1993; 75:2740-2744.
  4.  Brett, S., Cockcroft, J., Mant, T., Ritter, J., Chowienczyk, P.  Haemodynamic effects of inhibition of nitric oxide synthase and of L-arginine at rest and during exercise.  J. Hypertension.  1998; 16:429-435.
  5. Persson, M.G., Wiklund, N.P., Gustafsson, L.E.  Endogenous nitric oxide in single exhalations and the change during exercise.  Am. Rev. Resp. Dis.  1993; 148:1210-1214.
  6. Bode-Boger S.M., Boger, R.H., Schroder E.P., Frohlich, J.C.  Exercise increases systemic nitric oxide production in men.  J. Cardiovascular Risk.  1994; 1:173-178.
  7. Schaefer, A., Piquard, F., Geny, B., Doutreleau, S., Lampbert, E., Mettauer, B., Lonsdorfer, J.  L-arginine reduces exercise-induced increase in plasma lactate and ammonia.
  8. McConell, G.K., Kingwell, B.A.  Does nitric oxide regulate skeletal muscle glucose uptake during exercise?  Am. Coll. Sports Med.  2006; 34:36-41.
  9. McConell, G.K., Hunh N.N., Lee-Young, R.S., Canny, B.J., Wadley, G.D.  L-arginine infusion increases glucose clearance during prolonged exercise in humans.  Am. J. Physio.  2006; 290:60-66.
  10. Mendonca, J.R., Lancha, A.H. Jr, Curi, R.  Effect of chronic diet supplementation of ornithine, citrulline and arginine.  Med. & Sci. in Sports & Exercise.  1996; 28:82.
  11. Moore, T.A., Switzer, B.R., McMurray, R.G., Hall, J.E.  Growth hormone response to oral arginine supplementation.  Med. & Sci. in Sports & Exercise.  1998; 30:18.
  12. Chromiak, J.A., Antonio, J.  Use of amino acids as growth hormone-releasing agents by athletes. 
  13. Wu, G., Meininger, C., Knabe, D., Baze, F., Rhoads, J.  Arginine nutrition in development, health and disease.  Curr. Op. Clin. Nutrition and Metabolic Care.  2000; 3:59-66.


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