Back in 1996, in the first edition of Applied Metabolics, I suggested that a new class of sports supplements would soon appear on the market. My notion was based on the recent identification of a molecule called nitric oxide (NO), which among many other effects seemed to be a key player in the dilation of blood vessels. What caught my interest was the discovery that the amino acid L-arginine was the immediate nutritional precursor for the synthesis of NO in the body. Three NO synthase enzymes existed, and one of them was produced in the lining of blood vessels. As soon as arginine encountered this enzyme, it would be converted into NO, and the artery would dilate or widen. This meant greater blood flow, lower blood pressure, and a more efficient delivery of oxygen and nutrients to organs and tissues, including muscle. That latter effect made me realize the potential ergogenic effect of supplementing arginine as a precursor for NO synthesis. Prior to this, the most familiar sports use of arginine involved promotion of growth hormone release. Large doses of arginine could prod the pituitary gland to release GH. The mechanism involved arginine blocking the release of somatostatin, the primary inhibitor of GH release in the brain. For a while, arginine proved a popular supplement for bodybuilders, who ingested it in the hope of boosting their GH release. Subsequent studies, however, showed that this proved more of a dream than reality. For one, it turned out that only 40% of an oral dose of arginine ever made it into the blood. When ingested orally, arginine encounters a number of formidable barriers, such as the arginase enzyme in the gut that degrades it. Another problem emerged with arginine when other studies showed that if you ingested shortly before training (which was when it was most commonly ingested) it paradoxically lowered the release of GH induced by exercise. Finally, it became apparent that arginine worked most effectively as a GH-releaser when provided in intravenous delivery form at doses of 30 grams. This wasn't possible to emulate orally, since ingesting more than 10 grams of arginine produced nausea and gastrointestinal symptoms.
In my original article about NO written for the first edition of Applied Metabolics, I described how NO is produced from arginine and how NO works in the body. In the article, I made the bold prediction that NO-promoting supplements, based mainly on arginine, would soon be a big seller in the sports supplement category. My prescience proved correct. About a decade after I wrote that article, NO supplements were appearing everywhere. But the question is: Did they work as promised? Most of these NO supplements contained an average of 4 grams of arginine, and for good reason. The purveyors of these supplements knew that large doses of arginine would be intolerable for most people. Let's face it, the odds of continued sales of a . . .