Let the NO Flow

L-arginine is a conditionally essential amino acid, meaning that it’s essential in the human diet under certain conditions’among them periods of rapid growth, pregnancy and after injuries. The liver synthesizes arginine during the urea cycle, which is involved in the excretion of protein-metabolism waste products. The arginine the process produces, however, isn’t available to the rest of the body. Instead, an ar’ginine metabolite amino acid called L-citrulline circulates in the blood to the kidneys, where it’s converted back into L-arginine.

L-arginine is present in most protein foods, and the average person consumes about five grams a day. It first became popular with bodybuilders about 25 years ago, after the publication of the book Life Extension by Durk Pearson and Sandy Shaw. They quoted studies showing that arginine is a potent stimulator of growth hormone release. An Italian study published a few years later showed that taking a supplement containing 1,200 milligrams of both arginine and L-lysine produced a 600 percent increase in GH release in 14 young men. The results of that study, however, have never been replicated. Most scientists discount the use of oral arginine as a GH promoter because most studies that have shown significant GH release involved a 30-gram intravenous infusion.

More recently supplemental forms of L-arginine have been promoted as a nitric oxide booster. L-arginine is the immediate nutritional precursor of nitric oxide, which is a free radical and a type of gas that, among other things, acts as a potent dilator of blood vessels. The dilation of blood vessels gives you greater muscle pump during a workout, as well as increased nutrient and oxygen delivery to muscle.

Absorption of L-arginine in the body isn’t straightforward, however. An enzyme in the liver called L-arginase degrades a large oral dose of arginine, which helps explain why an infusion is more effective in GH release than an oral dose. Another problem, more directly related to nitric oxide synthesis, involves the presence of methylated forms of arginine that actually inhibit nitric oxide synthesis during protein digestion. Thus, for arginine to effectively increase nitric oxide synthesis, you must get an oral dose sufficient to overcome the formidable barriers to its uptake.

A new study sought to determine the optimal oral dose of L-arginine for purposes of nitric oxide synthesis.1 Twelve healthy people took free L-arginine for four weeks’free not because of price but because it wasn’t complexed with anything else, such as hydrochloric acid. (Oral intake of too much HCL causes gastrointestinal distress.)

The subjects took increasingly larger doses of arginine’three, then nine, 21 and 30 grams a day. Researchers measured not only arginine levels but also insulin, creatinine and several other substances. Five subjects reported side effects that included diarrhea, vomiting and nosebleed at the 21-gram dose. At the 30-gram level two of the subjects refused it, while nine subjects reported diarrhea, one had a headache, and another complained of dry mouth. The lower doses produced no side effects except with one person who had a nosebleed.

Arginine levels peak 60 minutes after oral intake and are still elevated after eight hours, though how much arginine is absorbed varies considerably. Based on their findings, the authors suggest that the best dose for ensuring nitric oxide synthesis is nine grams a day but caution that dosage must be tailored to each person. One way of doing that is to note the level of arginine that leads to side effects, then reduce it until the effects subside.

Unlike previous studies, this one found that arginine’at any dose’didn’t promote the release of insulin, nor did it affect glucose metabolism in any way. The only amino acid arginine lowered was glycine. The authors think that since both glycine and arginine are precursors of creatine synthesis, the arginine may have increased that. (Creatine helps build muscle and is good for the neural and cardiovascular systems.) On the other hand, the lack of effect on levels of creatinine, a metabolic waste product of creatine synthesis that is excreted through the kidneys in urine, appears to discount that theory. IM

1Evans, R.W., et al. (2004). Biochemical responses of healthy subjects during dietary supplementation with L-arginine. J Nutr Biochem. 15:534-39.